Myxoid Liposarcoma, Round Cell Liposarcoma, Synovial Sarcoma
Conditions
Brief summary
This pilot clinical trial studies the effect of recombinant interferon gamma on tissue in treating patients with soft tissue sarcoma. Interferon gamma may interfere with the growth of tumor cells.
Detailed description
PRIMARY OBJECTIVES: I. To determine whether systemic administration of interferon (IFN) gamma (recombinant interferon gamma) will increase class I major histocompatibility complex (MHC) expression in synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) tumors. SECONDARY OBJECTIVES: I. To determine whether systemic administration of IFN gamma will increase class II MHC expression in SS and MRCL tumors. II. To examine changes in the immune response to MRCL and SS by examining changes in the immune infiltrates, antibody response and antigen specific T cell response before and after IFN gamma treatment. OUTLINE: Patients receive recombinant interferon gamma subcutaneously (SC) every 7 days for 4 weeks before surgery. After completion of study, patients are followed up at 2 weeks post-surgery.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALRecombinant Interferon Gamma
Given subcutaneously weekly for four weeks prior to surgery.
Sponsors
National Cancer Institute (NCI)
Horizon Pharma USA, Inc.
Fred Hutchinson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
100 mcg/m2 weekly injection for four weeks
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. A diagnosis of synovial sarcoma and myxoid/round cell liposarcoma 2. Male or female subject, 18 or older 3. A superficial tumor easily and safely accessible for a research biopsy or are being considered for resection or biopsy of their tumor as part of standard of care and have recent pathology. 4. Zubrod performance status of '0-2' or Karnofsky score \> 60% 5. No treatment with systemic anti-cancer treatment (chemotherapy or biologics) within 2 weeks of starting interferon gamma 6. Patients with a history of coronary artery disease must have had a normal stress test within 180 days of starting IFN gamma 7. Must have been off metformin for at least 2 weeks prior to starting IFN gamma 8. No use of full dose, therapeutic anti-coagulation. However, low dose warfarin for catheter prophylaxis or acetylsalicylic acid are acceptable. 9. No thrombotic event within 6 months (deep vein thrombosis, pulmonary embolism) of starting IFN gamma
Exclusion criteria
1. Active infection requiring oral or intravenous antibiotics 2. Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence. Women of childbearing potential must have a negative pregnancy test within two weeks prior to entry. 3. Serum creatinine \> 1.5 mg/dL or Glomerular Filtration Rate \< 50 4. Significant hepatic dysfunction (SGOT \> 150 IU or \> 3x upper limit of normal; bilirubin \> 1.6 mg/dL; prothrombin time \> 1.5x control). 5. Known central nervous system (CNS) metastasis. Once CNS metastasis have been treated these patients may participate if they are otherwise good trial candidates. 6. Current treatment with steroids (must be discontinued 1 week before starting IFN gamma) 7. Hemoglobin A1C \> 8.5% 8. Uncontrolled hypertension, blood pressure (BP) \> 150/100 mmHg; patients with elevated BP may enroll once BP is corrected 9. Cancer/testis antigen 1B (NY-ESO-1) specific T cell therapy within 1 year of starting on the trial 10. New (\< 6 months) cardiac arrhythmia (electrocardiogram \[EKG\] should be performed within 2 weeks of starting IFN gamma). 11. History of clinically significant congestive heart failure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Class I Major Histocompatibility Complex (MHC) Expression After Treatment With IFN Gamma | Baseline to up to 2 weeks post-surgery | It would be highly relevant to observe marked increase macrophages (effect size \> 2.5). Four patients gives over 90% power to detect such a large increase with a two-tailed alpha of 0.05. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| MHC Class II Expression | Baseline to 2 weeks post biopsy. | To determine whether systemic administration of IFNg will increase class II MHC expression in SS and MRCL tumors. |
| Changes in Immune Response | Baseline to 2 weeks post biopsy | To examine changes in the immune response to MRCL and SS by examining changes in the immune infiltrates, antibody response and antigen specific T cell response before and after IFNg treatment. |
Countries
United States
Participant flow
Recruitment details
Recruitment was done in the Seattle Cancer Care Alliance medical clinic, or by patient referral.
Participants by arm
| Arm | Count |
|---|---|
| Basic Science (Interferon Gamma and MHC Expression) Patients receive recombinant interferon gamma SC every 7 days for 4 weeks before surgery or thrice weekly for 2 weeks before surgery.
Laboratory Biomarker Analysis: Correlative studies
Recombinant Interferon Gamma: Given SC | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Patient refused to complete post-tx bx | 1 |
Baseline characteristics
| Characteristic | Basic Science (Interferon Gamma and MHC Expression) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Change in Class I Major Histocompatibility Complex (MHC) Expression After Treatment With IFN Gamma
It would be highly relevant to observe marked increase macrophages (effect size \> 2.5). Four patients gives over 90% power to detect such a large increase with a two-tailed alpha of 0.05.
Time frame: Baseline to up to 2 weeks post-surgery
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Basic Science (Interferon Gamma and MHC Expression) | Change in Class I Major Histocompatibility Complex (MHC) Expression After Treatment With IFN Gamma | Pre-treatment | 8.91 percentage of MHC Class I+ on tumor cell |
| Basic Science (Interferon Gamma and MHC Expression) | Change in Class I Major Histocompatibility Complex (MHC) Expression After Treatment With IFN Gamma | Post-treatment | 26.6 percentage of MHC Class I+ on tumor cell |
Secondary
Changes in Immune Response
To examine changes in the immune response to MRCL and SS by examining changes in the immune infiltrates, antibody response and antigen specific T cell response before and after IFNg treatment.
Time frame: Baseline to 2 weeks post biopsy
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Basic Science (Interferon Gamma and MHC Expression) | Changes in Immune Response | Pre-treatment | 0.14 percentage of T cells |
| Basic Science (Interferon Gamma and MHC Expression) | Changes in Immune Response | Post-treatment | 0.82 percentage of T cells |
Secondary
MHC Class II Expression
To determine whether systemic administration of IFNg will increase class II MHC expression in SS and MRCL tumors.
Time frame: Baseline to 2 weeks post biopsy.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Basic Science (Interferon Gamma and MHC Expression) | MHC Class II Expression | Pre-treatment | 2.556 percentage of MHC Class II on tumor cell |
| Basic Science (Interferon Gamma and MHC Expression) | MHC Class II Expression | Post-treatment | 6.125 percentage of MHC Class II on tumor cell |