Recombinant Interferon Gamma in Treating Patients With Soft Tissue Sarcoma

A Pilot Study to Test Whether Systemic Interferon Gamma Increases Tumor Class I MHC Expression in Patients With Synovial Sarcoma and Myxoid/Round Cell Liposarcoma

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.

Study Overview

• Status: Terminated
• Conditions: Myxoid Liposarcoma; Synovial Sarcoma; Round Cell Liposarcoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Recombinant Interferon Gamma

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Basic science (interferon gamma and MHC expression); Patients receive recombinant interferon gamma subcutaneously weekly for 4 weeks before surgery.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Recombinant Interferon Gamma; Given subcutaneously weekly for four weeks prior to surgery.; Other Names: Gamma Interferon (GEN); Gamma Interferon-SCH; Gamma-Interferon; Ginterferon; IFN-g; Interferon Gamma; Interferon Gamma (BIO); Interferon, Gamma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline to up to 2 weeks post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MHC Class II Expression	To determine whether systemic administration of IFNg will increase class II MHC expression in SS and MRCL tumors.	Baseline to 2 weeks post biopsy.
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.	Baseline to 2 weeks post biopsy

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI); Horizon Pharma USA, Inc.

Publications and helpful links

General Publications

• Schroeder BA, Black RG, Spadinger S, Zhang S, Kohli K, Cao J, Mantilla JG, Conrad EU, Riddell SR, Jones RL, Yee C, Pollack SM. Histiocyte predominant myocarditis resulting from the addition of interferon gamma to cyclophosphamide-based lymphodepletion for adoptive cellular therapy. J Immunother Cancer. 2020 Apr;8(1):e000247. doi: 10.1136/jitc-2019-000247.

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2013
• Primary Completion (Actual): June 1, 2018
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: October 4, 2013
• First Submitted That Met QC Criteria: October 4, 2013
• First Posted (Estimate): October 8, 2013

Study Record Updates

• Last Update Posted (Actual): July 10, 2019
• Last Update Submitted That Met QC Criteria: June 19, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Neoplasms, Adipose Tissue; Sarcoma; Liposarcoma; Liposarcoma, Myxoid; Sarcoma, Synovial; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Interferons; Interferon-gamma
• Other Study ID Numbers: 2705.00 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); P30CA015704 (U.S. NIH Grant/Contract); NCI-2013-01779 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 2705 (Fred Hutchinson Cancer Research Center); K12CA076930 (U.S. NIH Grant/Contract); K23CA175167 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No