|
|
              
 |
Abstracts by Tom Swartz
This Phase I trial is currently recruiting patients. Radiolabeled monoclonal antibodies can locate tumor cells and deliver tumor-killing substances, such as radioactive iodine, to them without harming normal cells. Thus, the purpose of this trial is to study side effects and best dose of radiolabeled monoclonal antibody therapy in treating patients with refractory, recurrent, or advanced central nervous system or leptomeningeal cancer. Patients with the following sarcomas are eligible: rhabdomyosarcoma, soft tissue sarcoma, rhabdoid tumor of the central nervous system, desmoplastic small round-cell tumor, osteosarcoma, and Ewing's family of tumors. This is a dose-escalation study. Patients receive iodine I 131 monoclonal antibody 8H9 (^131I MOAB 8H9) intrathecally on day 1. Treatment repeats every 4 weeks for up to 2 courses (total of 2 injections) in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of ^131I MOAB 8H9 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 3-30 patients will be accrued for this study within 2-3 years. Patients of any age are eligible. This trial is taking place at Memorial Sloan-Kettering Cancer Center, New York.
NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine This Phase I trial is currently recruiting patients. The purpose of this trial is to estimate the safety of NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine given by PMED in patients with tumor type, including sarcomas, known to express NY-ESO-1 or LAGE-1 using frequency, severity, and duration of treatment-related adverse effects as endpoints. Eligible patients with tumor type known to express NY-ESO-1 or LAGE-1 antigen will be assigned to cohorts. NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine will be administered by PMED at a pressure of 500 psi using the XR-1 Powderject delivery device. The 4 microgram dosage of NY-ESO-1 will be administered as 4 X 1 microgram PMEDs in close proximity. Similarly, the 8 microgram dosage will be administered as 8 X 1 microgram PMEDs. The third cohort of patients will receive the 8 microgram dosage as a cluster dosage of 4 doses (day 1, 3, 5, 8) as 2 X 1 microgram PMEDs per day. Blood samples will be obtained at baseline, 2 weeks after each vaccination, prior to the second and third vaccination, and 4 weeks after the third vaccination for the assessment of clinical hematology, biochemistry measurements and immunology responses. Patients will be evaluated for toxicity throughout the study. DTH testing will be performed with NY-ESO-1 protein in all patients, with NY-ESO-1b peptide in HLA-A2+ patients and with NY-ESO-1 DP4 peptide in HLA-DP4+ patients at baseline and at the 2-week visit following the first and third vaccinations. NY-ESO-1 and/or LAGE-1 specific antibodies will be assessed in all patients by ELISA using recombinant NY-ESO-1 protein. NY-ESO-1 specific CD4+ and CD8+ T cells will be assessed in all patients by tetramer and/or ELISPOT assays. Disease status will be assessed at baseline and 4 weeks after the third vaccination in patients with measurable disease. The total expected enrollment is 15 patients. Patients 18 years of age and older are eligible. This trial is taking place at New York Presbyterian Hospital, New York, NY, and MD Anderson Cancer Center, Houston, Texas.
NY-ESO-1 Protein With Montanide and CpG 7909 as Cancer Vaccine in Several Tumors This Phase I trial is currently recruiting patients. The purpose of this study is to define the safety of an investigational cancer vaccine, and to evaluate whether patients develop a specific immunologic response to the NY-ESO-1 protein. Patients with any type of sarcoma are eligible. Patients will receive an investigational cancer vaccine every 3 weeks for a total of 4 treatments. It is given by injection underneath the skin in an extremity. A vaccine is a compound designed to strengthen the immune system to fight an illness such as infections or cancer. The vaccine used in this study is called NY-ESO-1 protein. NY-ESO protein is found in many cancers. Proteins such as NY-ESO-1 and their fragments are the targets the immune system needs to recognize cancer cells. If the immune system can recognize these antigens it may be able to kill the cells that carry them. NY-ESO-1 can be found at different stages of cancers, and is likely to be expressed at some point in the lifecycle of various cancers. Therefore this study tries to boost the immune system toward NY-ESO-1 protein regardless of whether it is found in your tumor or not. Since the investigators do not know whether different doses of the NY-ESO-1 protein may result in varying degrees of immune stimulation, the study will be randomized. The patient may receive either the lower dose of NY-ESO-1 protein (100 µg) or the higher dose (400 µg.) There is a 50:50 chance that the patient will receive the lower versus the higher dose. At this time, the investigators also have no way of knowing whether there will be any real difference in the effects between these doses. In either case, the patient will be receiving the NY-ESO-1 protein. In all studies to date, only the 100 µg dose has been used. There is no reason to think that the higher dose will be toxic, nor is there any reason at this time to think that the higher dose will be more effective at the immunological level, although it may be. The NY-ESO-1 protein vaccine will also be mixed with 2 substances, called adjuvants (the full names are: CPG 7909 and Montanide ISA-51). Adjuvants are substances to increase the vaccine’s ability to stimulate the immune system. By adding two adjuvants to the vaccine, it is hoped that the boosting of the immune system will be especially effective. All tests and treatments will be performed as an outpatient. The total expected enrollment is 20 patients. Patients 18 years of age and older are eligible. This trial is taking place at NYU Clinical Cancer Center, New York, NY, and NY Presbyterian- Columbia, New York, NY.
FR901228 in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma This Phase II trial is currently recruiting patients. FR901228 is a type of depsipeptide and belongs to the family of drugs called histone deacetylase inhibitors. Depsipeptide binds to and inhibits histone deacetylase, thereby affecting the regulation of gene expression and inducing cell differentiation, cell cycle arrest, and apoptosis. This agent also inhibits hypoxia-induced angiogenesis and depletes several HSP90-dependent oncoproteins. The purpose of this trial is to study how well FR901228 works in treating patients with metastatic or unresectable soft tissue sarcoma. Patients receive FR901228 IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 6 additional courses beyond documentation of CR. After completion of study treatment, patients are followed every 2 months. A total of 18-36 patients will be accrued for this study within approximately 1 year. Patients 18 years of age and older are eligible. This study is taking place at centers in Arizona, California, Georgia, Illinois, Kentucky, North Carolina, Ohio, South Carolina, and Virginia.
This Phase I trial is currently recruiting patients. OSI-774 is an experimental drug that may be useful in pediatric cancers resistant to standard treatments. The drug blocks a protein found on the surface of cells called epidermal growth factor receptor (EGFR) that can malfunction in cancerous cells. By blocking EGFR, the drug may block some of the effects that cause cancer cells to divide and spread. The drug may also block the growth of new blood vessels (angiogenesis) to a tumor. This study will investigate the effectiveness, side effects, and dosage of OSI-774 separately and together with temozolomide. It will also investigate the presence of EGFR and related proteins in patients' tumors. Patients with brain tumors, osteogenic sarcoma, rhabdomyosarcoma, and soft tissue sarcomas (excluding Ewing's) are eligible. Patients will be enrolled in small groups at gradually increasing dosages of OSI-774. This study will include approximately 24 patients less than 22 years of age. OSI-774 has undergone some tests in adults, but this will be its first trial in children. Patients will take the drug daily at home in 4-week cycles. The drug will be taken each morning in liquid form by mouth. After the first 4-week cycle, patients will continue with their daily dose of OSI-774. On the first 5 days of each cycle, patients will add a daily dose of temozolomide. Temozolomide is a drug in tablet form approved by the FDA for some brain tumors. It damages the DNA of cancer cells, and its effectiveness appears to be enhanced by drugs like OSI-774. During the first two cycles, patients will be examined by a doctor at least once a week and have weekly blood tests. Patients who agree will also give additional blood samples for research and permit tests on any otherwise available tumor tissue. After the first two cycles, patients will continue to have periodic exams and routine blood and other tests as necessary. This study is taking place at the National Cancer Institute, Bethesda, Maryland and Stanford Comprehensive Cancer Center (Lucile Packard Children's Hospital) Palo Alto, California. Additional information about this trial on Stanford's website can be viewed by clicking here.
This Phase III trial is currently recruiting patients. The purpose of this study is to provide compassionate use access to treatment with trabectedin (ET-743) before the drug is commercially available and reimbursable to patients who previously received treatment for soft tissue sarcoma. 1.5 mg/m2 of trabectedin reconstituted and diluted to 500 mL volume will be administered by central venous line over 24 hours at start of each 21-day treatment cycle. 20 mg of dexamethasone, an anti-inflammatory agent, will also be administered by vein 30 minutes before each trabectedin dose. The number of cycles will be response dependent. Sarcoma patients 18 years of age and older who have relapsed or have progressive disease following standard of care treatment prior to enrollment, or who are intolerant to standard of care treatment due to safety issues, are eligible. The total expected enrollment is 200 patients. The trial is taking place at centers in California, Idaho, Illinois, Kentucky, Massachusetts, New Jersey, Oregon, Pennsylvania, South Carolina, and Texas.
Safety, Tolerability and Maximum Tolerated Dose of Oral AP23573 in Combination With Doxorubicin This Phase I trial is currently recruiting patients. This study is designed to determine the safety, tolerability and maximum tolerated dose of Oral AP23573 in combination with Doxorubicin. Sarcoma patients 18 years of age and older are eligible. The treatment outline is not listed on the site. The total expected enrollment is 60 patients; the study started February 2006. The study is taking place at Pennsylvania Oncology Hematology Associates, Philadelphia, Pennsylvania (for further details contact: Hanne Harbison 215-829-6712) and with Dr. Sant P. Chawla, Santa Monica California (for further details contact: Vickie Chua 310-552-9999).
GW786034 in Treating Patients With Relapsed or Metastatic Soft Tissue Sarcoma This Phase II trial is currently recruiting patients. GW786034 is a multifunctional antiangiogenic agent derived from shark cartilage with potential antineoplastic activity. Neovastat competitively inhibits the binding of pro-angiogenic vascular endothelial growth factor (VEGF) to its cell receptor, thereby inhibiting endothelial cell proliferation. This agent also inhibits matrix metalloproteinases (MMPs), stimulates tissue plasminogen activator (tPA), and activates caspase-mediated apoptotic pathways in endothelial cells. GW786034 may stop the growth of soft tissue sarcoma by blocking blood flow to the tumor and by blocking some of the enzymes needed for tumor cell growth. The purpose of this trial is to study how well GW786034 works in treating patients with relapsed or metastatic soft tissue sarcoma. This is an open-label, nonrandomized, multicenter study. Patients are stratified according to tumor type (leiomyosarcoma vs. adipocytic tumor vs. synovial sarcoma vs. other soft tissue sarcoma). Patients receive oral GW786034 once daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression. After completing study treatment, patients are followed at 4 weeks and then every 3 months thereafter. A total of 148 patients (37 per stratum) will be accrued for this study. Soft tissue sarcoma patients 21 years of age and older are eligible. The following tumor types are excluded from this study: embryonal rhabdomyosarcoma, chondrosarcoma, osteosarcoma, Ewing tumors/primitive neuroectodermal tumors, gastrointestinal stromal tumors, dermofibromatosis sarcoma protuberans, inflammatory myofibroblastic sarcoma, neuroblastoma, malignant mesothelioma, mixed mesodermal tumors of the uterus. This trial is taking place at Daniel Den Hoed Cancer Center at Erasmus Medical Center, Rotterdam, Netherlands.
GW786034 In Patients With Relapsed Or Refractory Soft Tissue Sarcoma This Phase II trial is currently recruiting patients. GW786034 is a multifunctional antiangiogenic agent derived from shark cartilage with potential antineoplastic activity. Neovastat competitively inhibits the binding of pro-angiogenic vascular endothelial growth factor (VEGF) to its cell receptor, thereby inhibiting endothelial cell proliferation. This agent also inhibits matrix metalloproteinases (MMPs), stimulates tissue plasminogen activator (tPA), and activates caspase-mediated apoptotic pathways in endothelial cells. The purpose of this trial is to evaluate the activity and tolerability of GW786034 in subjects with advanced and/or metastatic soft tissue sarcoma who have relapsed following standard therapies or for whom no standard therapy exists and to characterize the pharmacokinetics of GW786034. Soft tissue sarcoma patients 21years of age and older are eligible. The following types of tumors are excluded: malignant glomus tumors, embryonal rhabdomyosarcoma, chondrosarcoma, osteosarcoma, Ewing/PNET, GIST, MSFT, DFSP, inflammatory myofibroblastic sarcoma, malignant mesothelioma, and neuroblastoma. The total expected enrollment is 148 patients. This trial is taking place at centers in Belgium, France, Hungary, The Netherlands, and the United Kingdom.
This Phase II trial is currently recruiting patients. The purpose of this trial is to compare the effectiveness of different combination chemotherapy regimens in treating children who have rhabdomyosarcoma, undifferentiated sarcoma, or ectomesenchymoma. This is a randomized, multicenter study. Patients are stratified according to risk status and window therapy eligibility (unfavorable risk and eligible vs. unfavorable risk and ineligible vs. favorable risk). The treatment outline is as follows:
Patients are followed every 2 months for 1 year, every 4 months for 2 years, and then annually thereafter. A total of 102-120 patients with unfavorable-risk disease (51 per treatment arm) will be accrued for this study within 2.5-3 years. A total of 20-30 patients with favorable-risk disease will be accrued for this study. Patients up to 20 years of age are eligible. The trial is taking place at centers in Alabama, Arizona, Arkansas, California, Connecticut, Delaware, the District of Columbia, Florida, Hawaii, Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Maine, Maryland, Michigan, Minnesota, Mississippi, Missouri, New Hampshire, New Jersey, New Mexico, New York, North Carolina, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, South Dakota, Tennessee, Texas, Utah, Vermont, Washington, West Virginia, Wisconsin, Australia, Canada, and Puerto Rico.
Intralesional Resection in Treating Patients With Chondrosarcoma of the Bone This Phase II trial is currently recruiting patients. Intralesional resection is a less invasive type of surgery for chondrosarcoma of the bone and may have fewer side effects and improve recovery. The purpose of this trial is to study how well intralesional resection works in treating patients with low-grade chondrosarcoma of the bone. Patients undergo intralesional resection (curettage with high-speed burr). Patients then receive local adjuvant treatment comprising of liquid nitrogen, phenol, alcohol, or argon beam to the excision site. The bone cavity is then filled with either polymethyacrylate cement or a bone graft (allograft or homograft). Patients may also have a metal plate installed at the wound site. Patients are followed every 3 months for 1 year and then every 6 months for 4 years. A total of 60 patients will be accrued for this study within 30-60 months. Patients 18 years of age and older are eligible. This trial is taking place at centers in Arkansas, Colorado, Florida, Michigan, Minnesota, Missouri, New Mexico, Oregon, Utah, and Washington.
Gemcitabine and Docetaxel to Treat Bone and Soft Tissue Cancers This Phase II trial is currently recruiting patients. This study will examine the side effects and possible benefits of the anti-cancer drugs gemcitabine (Gemzar) and docetaxel (Taxere) in patients with bone or soft tissue cancer (sarcoma); determine how the body absorbs and eliminates the drugs; and perform genetic studies on the tumor and try to grow the tumor in the laboratory or in animals. Patients 10 years of age and older with recurrent osteosarcoma, Ewing's sarcoma, and inoperable or recurrent inoperable chondrosarcoma may be eligible for this study. Participants receive gemcitabine and docetaxel in 21-day cycles as follows: Gemcitabine is given as a 90-minute infusion on days 1 and 8 of each cycle. Docetaxel is given as a 60-minute infusion following the gemcitabine infusion on day 8 of each cycle. Filgrastim is given as an injection under the skin either: 1) daily, beginning the day after each docetaxel infusion and continuing until the bone marrow is recovered from chemotherapy (usually 7 to 10 days); or 2) in a long-acting form on the day after the docetaxel infusion. Filgrastim boosts production of blood cells that have been depleted as a result of chemotherapy. Patients are taught to self-administer the injections. Treatment will continue for a total of 14 cycles or until the patient's tumor gets larger, side effects are unacceptable, the patient decides to stop treatment, or further treatment would not be in the patient's best interest. At the end of chemotherapy, patients will be monitored for treatment side effects and disease progress, initially every 3 months and then every 6 months until 2 years from finishing treatment. The total expected enrollment is 20 patients. This trial is taking place at the National Cancer Institute, Bethesda, Maryland.
Gemcitabine and Docetaxel in Treating Patients With Recurrent Osteosarcoma or Ewing's Sarcoma or Unresectable or Locally Recurrent Chondrosarcoma Drugs used in chemotherapy, such as gemcitabine and docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining gemcitabine with docetaxel may kill more tumor cells. The purpose of this trial is to study the effectiveness of combining gemcitabine with docetaxel in treating patients who have recurrent osteosarcoma, recurrent Ewing's sarcoma, or unresectable or locally recurrent chondrosarcoma. Patients are stratified according to diagnosis (recurrent osteosarcoma vs. recurrent Ewing’s sarcoma vs. unresectable or locally recurrent chondrosarcoma). Patients receive gemcitabine IV over 90 minutes on days 1 and 8 and docetaxel IV over 1 hour on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 9 and continuing until blood counts recover. Patients may receive pegfilgrastim SC on day 9 (once per course) as an alternative to G-CSF. Treatment repeats every 21 days for up to 14 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year and then every 6 months for 1 year. A maximum of 120 patients (40 per stratum) will be accrued for this study within 17-24 months. Patients 4 years of age and older are eligible. This trial is taking place at centers in California, the District of Columbia, Georgia, Illinois, Maryland, Massachusetts, Michigan, Minnesota, New York, and Texas.
GTI-2040 and Gemcitabine in Treating Patients With Metastatic or Unresectable Solid Tumors This Phase I trial is currently recruiting patients. GTI-2040 may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by making tumor cells more sensitive to gemcitabine. The purpose of this trial is to study the side effects and best dose of GTI-2040 and gemcitabine in treating patients with metastatic or unresectable solid tumors. Patients receive GTI-2040 IV continuously on days 2-16 of course 1 and on days 1-16 of all subsequent courses and gemcitabine IV over 30 minutes on days 1, 8, and 15 of course 1 and on days 2, 9, and 16 of all subsequent courses. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of GTI-2040 and gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional patients are treated at that dose. Approximately 18-40 patients will be accrued for this study within 6-20 months. Patients 18 years of age and older are eligible. This trial is taking place at the Cancer Therapy and Research Center, San Antonio, Texas, and the Veterans Affairs Medical Center also of San Antonio, Texas.
This Phase I trial is currently recruiting patients. GTI-2040 may increase the effectiveness of chemotherapy by making tumor cells more sensitive to the drugs. Giving GTI-2040 together with oxaliplatin and capecitabine may kill more tumor cells. The purpose of this trial is to study the side effects and best dose of capecitabine when given together with GTI-2040 and oxaliplatin in treating patients with locally advanced or metastatic colorectal cancer or other solid tumors. Patients receive GTI-2040 IV continuously on days 1-14, oral capecitabine twice daily on days 2-15, and oxaliplatin IV over 2 hours on day 2 of the first course. In all subsequent courses, capecitabine is administered on days 1-14, oxaliplatin is administered on day 1, and GTI-2040 is administered as in course 1. Courses repeat every 21 days in the absence of disease progression and unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 15-20 patients will be accrued for this study within 1 year. Patients 18 years of age and older are eligible. This trial is taking place at several centers in California.
Imatinib Mesylate in Treating Patients With Locally Advanced or Metastatic Dermatofibrosarcoma Protuberans or Giant Cell Fibroblastoma This Phase II trial is currently recruiting patients. Imatinib mesylate (Gleevec) may stop the growth of tumor cells by blocking the enzymes necessary for their growth. The purpose of this trial is to study how well imatinib mesylate works in treating patients with locally advanced or metastatic dermatofibrosarcoma protuberans or giant cell fibroblastoma. Patients receive oral imatinib mesylate twice daily for at least 14 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 14 weeks receive imatinib mesylate for 12 additional weeks. Patients with a partial or complete response at 14 weeks undergo surgical resection if possible. If surgical resection of all remaining tumor is not possible OR if complete resection is not achieved (section margins positive), patients continue to receive imatinib mesylate in the absence of disease progression. Patients are followed monthly for 6 months, every 3 months for 6 months, every 6 months for 2 years, and then annually thereafter. A total of 44 patients will be accrued for this study within 2 years. Patients 18 years of age and older are eligible. This trial is taking place at centers in Belgium and the Netherlands.
Imatinib Mesylate in Treating Patients With Locally Recurrent or Metastatic Dermatofibrosarcoma Protuberans (DFSP) or Transformed Fibrosarcomatous DFSP This Phase II trial is currently recruiting patients. Imatinib mesylate (Gleevec) may stop the growth of tumor cells by blocking the enzymes necessary for their growth. The purpose of this trial is to study how well imatinib mesylate works in treating patients with locally recurrent or metastatic dermatofibrosarcoma protuberans (DFSP) or transformed fibrosarcomatous DFSP (a type of soft tissue sarcoma). Patients receive oral imatinib mesylate once daily on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with documented tumor progression and no serious side effects may continue therapy at a higher dose for another 6 courses. Patients are followed every 6 months for 2 years and then annually for 3 years. A total of 20-40 patients will be accrued for this study within 10 months-3.4 years. Patients 18 years of age and older are eligible. This trial is taking place at centers in Arkansas, Colorado, Illinois, Indiana, Kansas, Michigan, Minnesota, Missouri, Montana, North Carolina, Ohio, South Carolina, Washington, West Virginia, and Wyoming.
Vaccine Trial for Clear Cell Sarcoma, Pediatric Renal Cell Carcinoma, Alveolar Soft Part Sarcoma and Children With Stage IV Melanoma This Phase I trial is currently recruiting patients. The purpose of this study is to learn if a vaccine made from the patient's own tumor cells then genetically modified to secrete GM-CSF will delay or stop the growth of the tumor. It will also look at the vaccine's effects on the immune system and the side effects of giving a vaccine made from a subject's own cancer cells. The trial is open to patients with clear cell sarcoma, alveolar soft part sarcoma, pediatric renal cell carcinoma (25 years of age and younger), and children (18 years of age and younger) with stage IV melanoma. The treatment outline is as follows:
Patients may participate in this study until one of the following happens: All vaccine created from the tumor has been given to the patient; the patient's disease worsens; the patient experiences an unacceptable and/or harmful side effect; the patient becomes pregnant; the patient is unable to follow the study plan; or the patient's doctor feels it is no longer in the best interest of the patient to continue. The expected enrollment is 36 patients. Iit is taking place at Dana-Farber Cancer Institute and Children's Hospital, Boston, Massachusetts.
Sorafenib in Treating Patients With Metastatic, Locally Advanced, or Recurrent Sarcoma This Phase II trial is currently recruiting patients. Sorafenib is a "targeted drug" engineered to inhibit something called the RAF kinase within cancer cells. RAF in turn is part of the RAS oncogene pathway. RAS is a gene which drives cell division and is overexpressed in many cancers. In addition to targeting RAF kinase, sorafenib also inhibits the VEGF and PDGF receptors on blood vessel cells. Thus, sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. The purpose of this trial is to study how well sorafenib works in treating patients with metastatic, locally advanced, or recurrent sarcoma. Patients are stratified according to sarcoma histology (angiosarcoma vs. malignant peripheral nerve sheath tumor vs. leiomyosarcoma vs. high-grade undifferentiated pleomorphic sarcoma [i.e., malignant fibrous histiocytoma] vs. fibrosarcoma vs. all other types of sarcoma). Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study, patients are followed at 4 weeks. A total of 222 patients will be accrued for this study. Patients 18 years of age and older are eligible. This trial is taking place at centers in Illinois, Michigan, New York, Ohio, South Carolina, and Texas.
Sorafenib in Treating Patients With Advanced or Recurrent Uterine Cancer This Phase II trial is currently recruiting patients. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor (see the sorafenib trial listed above) The purpose of this trial is to study how well sorafenib works in treating patients with advanced or recurrent uterine cancer, including recurrent uterine sarcoma. Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. A total of 74 patients will be accrued for this study. Patients 18 years of age and older are eligible. This trial is taking place at centers in California, Illinois, Indiana, Michigan, Missouri, Pennsylvania, Wisconsin, and Ontario Canada.
Trastuzumab in Treating Patients With Locally Advanced or Metastatic Synovial Sarcoma This Phase II trial is currently recruiting patients. Trastuzumab is a monoclonal antibody; it may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The purpose of this trial is to study how well trastuzumab works in treating patients with locally advanced or metastatic synovial sarcoma. Patients receive trastuzumab (Herceptin^®) IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 6 weeks until disease progression and then every 6 months for up to 2 years from study entry. A total of 20-40 patients will be accrued for this study within 10-40 months. Patients 18 years of age and older are eligible. This trial is taking place at centers in Illinois, Indiana, Iowa, Kansas, Missouri, Montana, North Carolina, Ohio, South Carolina, Utah, Washington, and Wyoming.
Chemo Drug Sensitivity Microculture (MiCK) Assay for Apoptosis This Phase II/III trial is currently recruiting patients. Identification of those patients who will or will not respond to a specific chemotherapy is important for making decisions regarding chemotherapy regimens as well as alternative management approaches. A laboratory test that could help to determine the sensitivity of an individual patient’s tumor cells to specific chemotherapeutic agents would be valuable in choosing the optimal chemotherapy regimen for that patient with an expectation of increasing the response rate to the therapy. Several types of in vitro assays that measure tumor cell survival following exposure to cytotoxic agents have been evaluated for their ability to predict chemotherapy outcomes. As a group, these assays are referred to as drug resistance assays. In a resistance assay, the surviving tumor cells can be detected directly by their exclusion or metabolism of specific dyes. Alternatively, since some tumor cells are proliferating, their survival can be detected by measurement of DNA synthesis by radiolabeled precursor incorporation or demonstration of clonogenic potential by growth into colonies in semi-solid culture medium. In several clinical studies, these assays were useful in detecting drug resistance and in predicting a poor prognosis for cancer patients. However, these resistance assays cannot detect sensitivity of an individual patient’s tumor cells to a specific drug. Therefore, new methods determining drug-sensitivity of the tumor cells of an individual patient and, thus, capable of both predicting a positive treatment outcome and guiding chemotherapy, would be of significant value. Recently, Dr. Kravtsov has developed an automated microculture kinetic (MiCK) assay for measuring drug induced apoptosis in tumor cells. Apoptosis is a distinct mode of cell death which occurs under physiological conditions and yet can be induced in malignant cells by chemical and physical factors including antitumor drugs. During the last decade, it has been recognized that chemotherapeutic agents exert their antitumor activity by triggering apoptosis in susceptible tumor cells. This implies that the MiCK assay for apoptosis provides a mechanism-based approach to studying effects of cytotoxic agents on tumor cells. Unlike “resistance” assays that measure a fraction of cells surviving drug exposure, the MiCK assay measures a fraction of tumor cells killed by a chemotherapeutic agent via mechanism of apoptosis. Therefore the MiCK assay determines drug sensitivity, rather than resistance. Recently the MiCK assay has been shown to predict complete remission rate and survival in acute myeloid leukemia patients better than clinical criteria did. In a limited study, the MiCK assay has been used to direct chemotherapy of the leukemia patients. The MiCK assay has also been used to study drug-induced apoptosis in solid tumors, including neuroblastoma and colon adenocarcinoma cell lines. More recent data has demonstrated that the MiCK assay can detect drug induced apoptosis in primary cultures of tumor cells isolated from patients with ovarian carcinoma, gastric carcinoma, metastatic breast cancer and high grade soft tissue sarcoma. DiaTech is a private company performing patient specific cancer chemosensitivity testing for patients and physicians. DiaTech Oncology is doing this clinical study to see if this new experimental MiCK technology assay will predict treatment outcome and can help to direct chemotherapy of cancer subjects, including those with soft tissue sarcoma. Patients must have tumor which is accessible and agree to undergo biopsies. The more viable tumor tissue is submitted for the study, the more chemotherapeutic agents can be tested against the tumor cells. Drug selection for testing against tumor cells will be based on the previous chemotherapy history of an individual patient with consideration of the future treatment plans. The drugs will be selected from a compendium of agents recommended for the treatment of the patient’s malignancy. Patients 18 to 85 years of age are eligible. The total expected enrollment is 150 patients. This trial is taking place at centers in Tennessee and Texas.
Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Refractory, Recurrent, or Advanced CNS or Leptomeningeal Cancer This Phase I trial is currently recruiting patients. Radiolabeled monoclonal antibodies can locate tumor cells and deliver tumor-killing substances, such as radioactive iodine, to them without harming normal cells. The purpose of this trial is to study the side effects and best dose of radiolabeled monoclonal antibody therapy in treating patients with refractory, recurrent, or advanced CNS or leptomeningeal cancer, including patients with Ewing's sarcoma/primitive neuroectodermal tumor, rhabdoid tumor, osteosarcoma, desmoplastic small rounded-cell tumor, and rhabdomyosarcoma. This is a dose-escalation study. Patients receive iodine I 131 monoclonal antibody 8H9 (^131I MOAB 8H9) intrathecally on day 1. Treatment repeats every 4 weeks for up to 2 courses (total of 2 injections) in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of ^131I MOAB 8H9 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 3-30 patients will be accrued for this study within 2-3 years (study began approximately August 2004). Patients of all ages are eligible. This study is taking place at Memorial Sloan-Kettering Cancer Center, New York.
Stem Cell Transplantation for Metastatic Solid Tumors This Phase II trial is currently recruiting patients. The goal of this study is to identify types of cancer that may be treatable with stem cell transplantation. Patients with a variety of different types of cancerous tumors, including sarcoma, that have metastasized and whose conditions have not improved with stand therapy, will be eligible to participate. Patients selected to participate in the study will undergo a procedure known as a "mini-transplant". The mini-transplant is a transplantation of stem-cells collected from a sibling (brother or sister) of the patient. Unlike traditional bone marrow transplants, the mini-transplant does not require intense chemotherapy or radiation therapy. Because of this, patients experience fewer and less severe side effects. The total expected enrollment is 150 patients. Patients 10 to 80 years of age are eligible. This study is taking place at the National Heart, Lung and Blood Institute, Bethesda, Maryland.
A Study of Anti-CTLA4 Antibody in People with Advanced Synovial Sarcoma This Phase II is currently recruiting patients. The investigators of this study will try to exploit some of the proteins made by synovial sarcoma (cancer-germ cell or cancer-testis antigens) as targets for the immune system. Specifically, they will investigate if immune-based therapy with anti-CTLA4 antibody once every 4 weeks for three treatments will activate the immune system enough to attack recurrent synovial sarcoma. In this study the tumor itself will serve as the "vaccine" or source of protein to activate tumor-fighting T cells with the anti-CTLA4. Anti-CTLA4 takes the brakes off the immune system to allow otherwise hidden immune responses to become more active. In so doing, there could be other side effects, such as immune system attacks against the normal organs of the body. Thus, the investigators will follow both the anti-tumor immune responses with frequent blood tests and follow and treat side effects people develop on this study to determine if anti-CTLA4 is worth pursuing in a larger number of patients with synovial sarcoma or other sarcomas. Patients 18 years of age and older are eligible. The total expected enrollment is 17 patients. The trial started July 2005 and it is expected to be completed in March 2007. This study is taking place at Memorial Sloan-Kettering Cancer Center, New York.
This Phase II trial is currently recruiting patients. The purpose of this trial is to study how well paclitaxel works in treating patients with locally advanced or metastatic soft tissue angiosarcoma or lymphangiosarcoma that cannot be removed by surgery. Patients receive paclitaxel IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses. A total of 15-30 patients will be accrued for this study. Patients 18 to 70 years of age are eligible. This trial is taking place at several centers in France.
This Phase III trial is currently recruiting patients. The purpose of this trial is to compare the progression-free and overall survival of patients with locally advanced or metastatic soft tissue sarcoma treated with doxorubicin vs. without ifosfamide and pegfilgrastim as first-line therapy. Patients are stratified according to WHO performance status (0 vs. 1), age group (less than 50 years of age vs. 50 years of age and over), presence of liver metastases (yes vs. no), histological grade (2 vs. 3), and participating center. Patients are randomized to 1 of 2 treatment arms as follows:
In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 8 weeks until disease progression and then every 12 weeks thereafter. The following sarcomas are eligible: malignant fibrous histiocytoma, myxoid and round cell liposarcoma, pleomorphic liposarcoma, or dedifferentiated liposarcoma, pleomorphic rhabdomyosarcoma, synovial sarcoma, myxofibrosarcoma (intermediate and high-grade), fibrosarcoma, leiomyosarcoma, angiosarcoma, malignant peripheral nerve sheath tumor, epithelioid sarcoma, alveolar rhabdomyosarcoma, unclassifiable sarcoma, not otherwise specified. A total of 450 patients will be accrued for this study within 4 years (study start 5/2003). Patients 18 to 60 years of age are eligible. This trial is taking place at centers in Austria, Belgium, Denmark, France, Germany, the Netherlands, Slovakia, Spain, and the United Kingdom.
Nelfinavir Mesylate in Treating Patients With Recurrent, Metastatic, or Unresectable Liposarcoma This phase I/II trial is not yet open for patient recruitment. Nelfinavir mesylate is a protease inhibitor which may help prevent cancer cells from spreading. The purpose of this trial is to study the side effects and best dose of nelfinavir mesylate and to see how well it works in treating patients with recurrent, metastatic, or unresectable liposarcoma. This is a phase I dose-escalation study followed by a phase II study. In the Phase I part of the study, patients receive oral nelfinavir mesylate twice daily in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of nelfinavir mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. In the Phase II part of the study, patients receive nelfinavir mesylate as in phase I at the MTD. A total of 40 patients will be accrued for this study. Patients 18 years of age and older are eligible. The location of this trial has not been identified.
A Study to Provide Access to Trabectedin in Patients with Soft Tissue Sarcoma Who Have Persistent or Recurrent Disease and Who Are Not Expected to Benefit from Currently Available Standard of Care Treatment This Phase II trial is currently recruiting patients. The purpose of this study is to provide access to treatment with trabectedin before the drug is commercially available and reimbursable to patients who previously received treatment for soft tissue sarcoma, who have relapsed or who are refractory to/intolerant of standard therapies. Trabectedin (ET-743, Yondelis) is the first of a new class of antitumor agents. Previous studies with trabectedin in patients who had been previously treated for soft tissue sarcoma have suggested that treatment with trabectedin resulted in tumor shrinkage, disease stabilization, and improved survival rates. However, hematologic toxicity, hepatic toxicity, and renal impairment were also observed in these patients. This is a single-arm, open-label, multicenter, study that is designed to provide access to trabectedin in patients with soft tissue sarcoma who are not expected to benefit from currently available therapeutic options for the treatment of soft tissue sarcoma. The safety profile of trabectedin will be evaluated to further assess the potential risks of trabectedin treatment in patients previously treated for soft tissue sarcoma. Safety evaluation will include physical examinations, monitoring of vital signs and adverse events, and assessing clinical laboratory tests and 12-lead electrocardiogram results. Eastern Cooperative Oncology Group (scale used by researchers to represent the level of activity a patient is capable of) performance status will also be assessed. The treatment outline is as follows: 1.5 mg/m2 trabectedin reconstituted and diluted to 500 mL volume will be administered by central venous line over 24 hours at start of each 21-day treatment cycle; 20 mg dexamethasone, an anti-inflammatory agent, will be administered by vein 30 minutes before each trabectedin dose. The number of cycles will be response dependent. The total expected enrollment for this trial is 200 patients. Patients 18 years of age and older are eligible. This trial is taking place at centers in California, Idaho, Illinois, Massachusetts, Michigan, Minnesota, New Jersey, New York, Oregon, South Carolina, and Canada.
Phase II Study of Vinorelbine + Cyclofosfamide Among Patients With Refractory Tumors or in Relapse This phase II trial is currently recruiting patients. The purpose of this study is to determine the antitumor activity of vinorelbine + cyclofosfamide in patients with a refractory tumor or in relapse in rhabdomyosarcomas and other soft part tissue tumors, Ewing’s tumors, osteosarcomas, neuroblastomas or medulloblastomas. The total expected enrollment is 210 patients (the study started in June 2003). Patients 12 months to 25 years of age are eligible. This study is taking place at the Institut Gustave-Roussy, Villejuif, France.
Combination Chemotherapy, PEG-Interferon Alfa-2b, and Surgery in Treating Patients With Osteosarcoma This Phase III trial is currently recruiting patients. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Biological therapies, such as PEG-interferon alfa-2b, may interfere with the growth of tumor cells. Giving combination chemotherapy before surgery may shrink the tumor so it can be removed. Giving combination chemotherapy together with PEG-interferon alfa-2b after surgery may kill any remaining tumor cells. It is not yet known whether giving combination therapy together with PEG-interferon alfa-2b is more effective than two different combination chemotherapy regimens alone after surgery in treating osteosarcoma. Thus, the purpose of this trial is to study combination chemotherapy followed by surgery and two different combination chemotherapy regimens with or without PEG-interferon alfa-2b to compare how well they work in treating patients with osteosarcoma. The treatment outline is as follows:
Arm II (MAPIE; weeks 12-40): Patients receive doxorubicin IV continuously over 48 hours on days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23, 27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16, 24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in weeks 16, 24, and 32. In both groups, treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 1½-3 months for 2 years, every 2-4 months for 2 years, every 6 months for 6 years, and then every 6-12 months thereafter. A total of 1,400 patients (630 good responders and 770 poor responders) will be accrued for this study within 4 years. Patients between 5 and 40 years of age are eligible. Patients who have received prior treatment for osteosarcoma are not eligible. This trial is taking place at centers in Canada, Germany, Norway, and the United Kingdom.
This Phase II/III trial is currently recruiting patients. In 1986, St. Jude Children’s Research Hospital researchers initiated a trial (OS86) of ifosfamide, cisplatin, doxorubicin, and high-dose methotrexate. A subsequent trial (OS91), which was completed in 1997, substituted carboplatin for cisplatin. The 5-year survival estimates for patients with localized osteosarcoma were 69.2%±7.4% for those treated on OS86 and 73.1%±7.0% for those treated on OS91 (P=0.84). The results of OS91 demonstrated that the carboplatin and ifosfamide combination has substantial antitumor activity. When used with doxorubicin and high-dose methotrexate to treat localized osteosarcoma, this combination yielded outcomes comparable to those of trials using cisplatin-based therapy, with less long-term toxicity. On the basis of these results and the results of other studies that have eliminated high-dose methotrexate, St. Jude Children’s Research Hospital researchers are conducting this current trial to evaluate ifosfamide, carboplatin, and doxorubicin as an up-front therapy before surgery for localized and resectable osteosarcoma. The investigators believe that high-dose methotrexate may interfere with the dose-intensive delivery of the other agents, and thus, has been eliminated from this study. A total of 70 patients will be recruited for this study. Patients who have received prior chemotherapy are not eligible. Patients 25 years of age and younger are eligible. This trial is taking place at St. Jude Children's Research Hospital, Memphis, Tennessee.
Vincristine, Doxorubicin, Cyclophosphamide and Dexrazoxane (VACdxr) With or Without ImmTher for Newly Diagnosed High Risk Ewing's Sarcoma This Phase II trial is currently recruiting patients. Vincristine, Doxorubicin, Cyclophosphamide and Dexrazoxane are widely used drugs in the treatment of sarcomas. ImmTher is an investigational agent which stimulates the body's white blood cells to attack and kill tumor cells. The goal of this study is to see if treatment with vincristine, doxorubicin, cyclophosphamide and dexrazoxane (VACdxr) given in high doses with or without ImmTher will help patients with Ewing's sarcoma live longer. The safety of these treatments will also be studied. The total expected enrollment is 104 patients. Patients between 3 and 60 years of age are eligible. This trial is taking place at University of Texas M.D. Anderson Cancer Center, Houston, Texas.
A phase II trial to assess the activity of Gemcitabine and Docetaxel as first line chemotherapy treatment in patients with unresectable leiomyosarcoma This phase II trial is currently recruiting patients. It is open to patients that have histologically proven leiomyosarcoma of the uterus or other sites considered unresectable for cure. No previous chemotherapy is allowed, but patients may have received prior radiation provided it is completed >6 weeks prior to inclusion. It is a study of gemcitabine and docetaxel as a first line treatment. A total of 44 patients will be recruited. The trial is taking place in the United Kingdom. For further details, contact Jennifer Morrison.
Phase III Randomized Study of Doxorubicin With Versus Without Ifosfamide and Pegfilgrastim in Patients With Locally Advanced or Metastatic Soft Tissue Sarcoma This Phase III trial is currently recruiting patients. The purpose of this trial is to compare the progression-free and overall survival of patients with locally advanced or metastatic soft tissue sarcoma treated with doxorubicin with vs. without ifosfamide and pegfilgrastim as first-line therapy. Patients are stratified according to WHO performance status (0 vs. 1), age group (less than 50 years of age vs. 50 years of age and over), presence of liver metastases (yes vs. no), histological grade (2 vs. 3), and participating center. Patients are randomized to 1 of 2 treatment arms as follows:
In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 8 weeks until disease progression and then every 12 weeks thereafter. The following sarcomas are eligible: malignant fibrous histiocytoma, myxoid and round cell liposarcoma, pleomorphic liposarcoma, or dedifferentiated liposarcoma, pleomorphic rhabdomyosarcoma, synovial sarcoma, myxofibrosarcoma (intermediate and high-grade), fibrosarcoma, leiomyosarcoma, angiosarcoma, malignant peripheral nerve sheath tumor, epithelioid sarcoma, alveolar rhabdomyosarcoma, unclassifiable sarcoma, not otherwise specified. A total of 450 patients will be accrued for this study within 4 years (study start 5/2003). Patients 18 to 60 years of age are eligible. This trial is taking place at centers in Austria, Belgium, Denmark, France, Germany, the Netherlands, Slovakia, Spain, and the United Kingdom.
Bendamustin Hydrochloride in Patients with Soft Tissue Sarcoma This Phase II trial is currently recruiting patients. Bendamustin is a bifunctional alkylating agent with low toxicity that produces both single and double strand breaks of DNA. It has shown anti-tumor activity against Hodgkin’s and non-Hodgkin’s lymphomas, multiple myeloma, and chronic lymphatic leukemia. The aims of this trial are to evaluate the efficacy of bendamustin in patients with metastatic soft tissue sarcoma who have progressed after or during an anthracycline-based chemotherapy and to assess its toxicity. Patients 18 years of age and older are eligible. This trial is taking place at Medical center II, University of Tuebingen, Tuebingen, Germany.
ZD1839 and Oral Irinotecan in Treating Young Patients with Refractory Solid Tumors This Phase I trial is currently recruiting patients. The purpose of this trial is to find the largest dose of the drug irinotecan, in combination with ZD1839, that can be given safely to children and to learn the good and bad effects. Studies performed in the laboratory have shown that ZD1839 helps make available the orally administered irinotecan. In this study the intravenous formula of irinotecan will be given orally on days 1-5 and days 8-12. The dose of ZD1839 will be a fixed dose and will be administered orally on days 1-12. Each course of treatment will consist of 21 days. The administration of irinotecan on day 12 of course 1 and day 2 of course 2 will be an intravenous administration. All other doses and subsequent courses will consist of an orally administered dose. The total expected enrollment is 30 patients. Patients up to 21 years of age are eligible. This trial is taking place at St. Jude Children's Research Hospital, Memphis, Tennessee.
This Phase II trial is currently recruiting patients. Pemetrexed disodium (Alimta) is a potent new antifolate which inhibits many folate-dependent reactions that are essential for cell proliferation. Its primary target is thymidylate synthase but it also inhibits folate-dependent enzymes involved in purine synthesis. Cells that are resistant to antifolates are generally less resistant to pemetrexed, irrespective of the mechanism of resistance. Pemetrexed has shown good activity in preclinical models with human tumor cells and xenografts. In the majority of clinical trials of pemetrexed, the dose-limiting toxic effect is neutropenia; other side-effects are mostly gastrointestinal. Preclinical studies indicate that the toxic effects of pemetrexed can be reduced by dietary folate, resulting in an improved therapeutic index. Low folate status is also associated with higher levels of toxicity in patients. As a single agent pemetrexed has shown good activity against non-small-cell lung cancer, squamous-cell carcinoma of head and neck, colon cancer, and breast cancer, and it appears to be particularly active in combination with cisplatin against non-small-cell lung cancer and mesothelioma. The purpose of this trial is to study how well pemetrexed disodium works in treating patients with recurrent and unresectable or metastatic chondrosarcoma. Patients are stratified according to prior chemotherapy (yes vs. no). The treatment outline is as follows. Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days* in the absence of disease progression or unacceptable toxicity (NOTE: *The duration of course 1 is 28 days; the duration of all subsequent courses is 21 days). Beginning 7 days before the first dose of pemetrexed disodium and continuing until 21 days after the completion of pemetrexed disodium, patients receive cyanocobalamin (vitamin B-12) intramuscularly once every 63 days and oral folic acid once daily. Patients achieving a complete response (CR) receive 2 additional courses beyond CR. Patients achieving a confirmed partial response (PR) that is resectable, proceed to surgical resection and then receive 2 additional courses of therapy after recovering from surgery. Patients achieving a confirmed PR that is not resectable continue treatment in the absence of disease progression or unacceptab |
