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

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

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

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.

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).