A Study of Anti-CTLA-4 Antibody in Patients With Advanced Synovial Sarcoma

Study Overview
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Brief Summary
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The purpose of this study is to determine whether immune therapy with anti-CTLA-4 antibody is effective in people with advanced synovial sarcoma.

Detailed Description
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Approximately 750-900 people in the United States each year develop synovial sarcoma, a rare form of cancer of connective tissue. This tumor frequently metastasizes to other parts of the body such as the lungs. Chemotherapy can sometimes decrease the size of the recurrent tumors, but these results are usually only temporary, and the tumors grow again. We are trying to exploit some of the proteins made by synovial sarcoma (cancer-germ cell or cancer-testis antigens) as targets for the immune system. Specifically, we are investigating if immune-based therapy with anti-CTLA-4 antibody once every 3 weeks for three treatments will activate the immune system enough to attack recurrent synovial sarcoma. In this study the tumor itself serves as the vaccine or source of protein, as we try to activate tumor-fighting T cells with the anti-CTLA-4. Anti-CTLA-4 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. We 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-CTLA-4 is worth pursuing in a larger number of patients with synovial sarcoma or other sarcomas.

Official Title
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A Phase II Study of Anti-CTLA-4 Antibody in Advanced Synovial Sarcoma Patients

Conditions
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Synovial Sarcoma

Intervention / Treatment
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* Biological: ipilimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented synovial sarcoma. Patients with metastatic disease or locally recurrent disease who have failed or refused standard treatment. The disease must be measurable by RECIST. Expected survival of at least 6 months. Weight at least 35 kg. ECOG performance scale 0-2. At least 3 weeks since major surgery, and at least 3 weeks since completing radiation therapy or chemotherapy (6 weeks for patients receiving mitomycin C). Resolution of toxicity from previous treatment to NCI-CTC grade 1 or less before treatment. Adequate bone marrow, renal and hepatic function. Able and willing to give valid written informed consent. Exclusion Criteria: Clinically significant heart disease (NYHA Class III or IV). Other serious illnesses, e.g. serious infections requiring antibiotics or bleeding disorders. History of autoimmune disease. Serious intercurrent illness, requiring hospitalization. Patients with a second cancer diagnosis in the last five years, except for basal cell carcinoma, completely resected, or cervical carcinoma in situ (CIN), completely resected. Known HIV positivity. Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available. Chronic use of immunosuppressive drugs such as systemic corticosteroids. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study. Lack of availability for immunological and clinical follow-up assessments. Participation in any other clinical trial involving another investigational agent within 3 weeks prior to enrollment. Pregnancy or breast feeding. Refusal or inability to use effective means of contraception (all men, and women with childbearing potential).

Ages Eligible for Study
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Minimum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ipilimumab<br>Three doses of ipilimumab, 3 mg/kg, were administered by intravenous infusion at 3-week intervals. A 6-week observation period followed the final dose. | Biological: ipilimumab<br> <br> * Other names: Yervoy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Best Tumor Response as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST). | Computed tomography (CT) scans were performed at screening, and week 10. Response was assessed using RECIST version 1.0 (Therasse P et al. J Natl Cancer Inst 92:205-216). Per RECIST, target lesions are categorized as follows: complete response (CR): disappearance of all target lesions (no evaluable disease); partial response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; progressive disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; stable disease (SD): small changes that do not meet above criteria. | up to 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With NY-ESO-1 Specific Immunity as Measured by Antibody Response to NY-ESO-1 or LAGE-1 | Blood samples were taken at baseline and weeks 4, 7, 10 and 13. Humoral immunity was assessed by measurement of antibodies to NY-ESO-1 or LAGE by enzyme-linked immunosorbent assay (ELISA). Positive results are reported as antibodies to NY-ESO-1- and/or LAGE-1-specific Total IgG (reciprocal titer). | up to 13 weeks | 
| Number of Subjects Reporting Adverse Events (AEs) | All adverse events (AEs) which occurred after signed informed consent were documented in the source records and on the respective AE Case Report Form (CRF). Toxicity was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Scale (Version 3.0). | up to 13 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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synovial sarcoma, immunotherapy, cancer-testis antigen, cancer-germ cell antigen, soft tissue sarcoma, SYT-SSX chromosomal translocation