Back to resultsA Study of Anti-CTLA-4 Antibody in Patients With Advanced Synovial Sarcoma
Primary Purpose
Synovial Sarcoma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ipilimumab
Sponsored by
About this trial
This is an interventional treatment trial for Synovial Sarcoma focused on measuring synovial sarcoma, immunotherapy, cancer-testis antigen, cancer-germ cell antigen, soft tissue sarcoma, SYT-SSX chromosomal translocation
Eligibility Criteria
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).
Sites / Locations
- Memorial Sloan-Kettering Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ipilimumab
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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).
Full Information
NCT ID
NCT00140855
First Posted
August 30, 2005
Last Updated
October 3, 2022
Sponsor
Ludwig Institute for Cancer Research
Collaborators
Medarex
1. Study Identification
Unique Protocol Identification Number
NCT00140855
Brief Title
A Study of Anti-CTLA-4 Antibody in Patients With Advanced Synovial Sarcoma
Official Title
A Phase II Study of Anti-CTLA-4 Antibody in Advanced Synovial Sarcoma Patients
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Terminated
Why Stopped
Study discontinued due to poor accrual.
Study Start Date
June 8, 2005 (Actual)
Primary Completion Date
April 18, 2007 (Actual)
Study Completion Date
July 1, 2007 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ludwig Institute for Cancer Research
Collaborators
Medarex
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Synovial Sarcoma
Keywords
synovial sarcoma, immunotherapy, cancer-testis antigen, cancer-germ cell antigen, soft tissue sarcoma, SYT-SSX chromosomal translocation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ipilimumab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
ipilimumab
Other Intervention Name(s)
Anti-CTLA-4 monoclonal antibody, monoclonal antibody MDX-010, Yervoy
Primary Outcome Measure Information:
Title
Number of Subjects With Best Tumor Response as Measured by the Response Evaluation Criteria in Solid Tumors (RECIST).
Description
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.
Time Frame
up to 10 weeks
Secondary Outcome Measure Information:
Title
Number of Subjects With NY-ESO-1 Specific Immunity as Measured by Antibody Response to NY-ESO-1 or LAGE-1
Description
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).
Time Frame
up to 13 weeks
Title
Number of Subjects Reporting Adverse Events (AEs)
Description
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).
Time Frame
up to 13 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert G Maki, MD PhD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
10655437
Citation
Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.
Results Reference
background
PubMed Identifier
23554566
Citation
Maki RG, Jungbluth AA, Gnjatic S, Schwartz GK, D'Adamo DR, Keohan ML, Wagner MJ, Scheu K, Chiu R, Ritter E, Kachel J, Lowy I, Old LJ, Ritter G. A Pilot Study of Anti-CTLA4 Antibody Ipilimumab in Patients with Synovial Sarcoma. Sarcoma. 2013;2013:168145. doi: 10.1155/2013/168145. Epub 2013 Feb 27.
Results Reference
result
Links:
URL
http://www.mskcc.org/mskcc/html/2270.cfm?peds=no&team=Soft+Tissue+Sarcoma&x=18&y=19
Description
Link to MSKCC Sarcoma Clinical trial web site highlighting anti-CTLA4 protocol
Learn more about this trial
A Study of Anti-CTLA-4 Antibody in Patients With Advanced Synovial Sarcoma
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