Neoplasms

All Conditions

Rare Diseases

Sarcoma

Liposarcoma

Liposarcoma, Myxoid

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Adipose Tissue

Soft Tissue Sarcoma

Myxoid Liposarcoma

Antineoplastic Agents

All Drugs and Chemicals

Trabectedin

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients undergo a biopsy at baseline and then receive trabectedin for up to 4 cycles. Beginning 1 week after completion of cycle 2 and prior to cycle 3, patients undergo a second biopsy. Patients who achieve clinical benefit (CR, PR, SD) after the first post-treatment scan and who continue trabectedin for 4 cycles undergo a third biopsy after cycle 4.

Biopsy

Laboratory Biomarker Analysis

Seth Pollack

This research trial studies the immune changes following trabectedin in patients with sarcoma that has spread to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Analyzing tumor tissue may help to understand the changes in immune cells in or around the tumor or if there is an increase in immune cells in the tumor after receiving trabectedin.

PRIMARY OBJECTIVES:

I. Percentage of tumor tissue in pre- and post-treatment biopsies comprised of T-cells, as determined by flow cytometry.

SECONDARY OBJECTIVES:

I. To explore additional potential biomarkers including: numbers of tumor associated macrophage (TAM) in tumor II. To explore additional potential biomarkers including: phenotype (classically activated macrophages \[M1\] versus \[vs\] alternatively activated macrophages \[M2\]) as characterized by CD163, CD115, CD206 on infiltrating TAM.

III. To explore additional potential biomarkers including: phenotype of T cells infiltrating tumor (CD4, CD8, markers of CD4 phenotype including FoxP3 and memory).

IV. To explore additional potential biomarkers including: expression T cell inhibitory markers (PD-1, CTLA-4, TIM3).

V. To explore additional potential biomarkers including: recognition of autologous tumor by expanded tumor infiltrating lymphocyte lines.

VI. To explore additional potential biomarkers including: in tumor infiltrating lymphocyte (TIL) expanded from myxoid/round cell liposarcomas, recognition of cancer testis antigens.

OUTLINE:

Patients undergo a biopsy at baseline and then receive trabectedin for up to 4 cycles. Beginning 1 week after completion of cycle 2 and prior to cycle 3, patients undergo a second biopsy. Patients who achieve clinical benefit (complete response \[CR\], partial response \[PR\], stable disease \[SD\]) after the first post-treatment scan and who continue trabectedin for 4 cycles undergo a third biopsy after cycle 4.

After completion of study, patients are followed up for 30 days.

Immune Changes Following Trabectedin in Patients With Metastatic or Unresectable Sarcoma

An Analysis of the Changes in the Sarcoma Tumor Immune Microenvironment Following Trabectedin

Analysis will be performed using a Wilcoxon matched-pairs assigned rank test as these will be paired samples where parametric distribution cannot be assumed. T cell receptor (TCR) sequencing, immunohistochemistry and gene expression analysis will all be used in order to confirm the primary endpoint.

Gene expression will be analyzed using differential cluster analysis in order to look for patterns and gene groups that are differentially expressed in the post-treatment samples and such gene groups will be represented by heatmaps in order to illustrate this quantitative information. TCR fraction, clonality, and maximum (max) frequency will be compared between pre and post treatment samples.

Gene expression will be analyzed using differential cluster analysis in order to look for patterns and gene groups that are differentially expressed in the post-treatment samples and such gene groups will be represented by heatmaps in order to illustrate this quantitative information. TCR fraction, clonality, and max frequency will be compared between pre and post treatment samples.

National Cancer Institute (NCI)

Janssen Pharmaceuticals

Fred Hutchinson Cancer Center

Skin and Connective Tissue Diseases

Sarcoma, Synovial

Neoplasms, Connective Tissue

Synovial Sarcoma

Anti-Infective Agents

Interferons

Interferon-gamma

Antiviral Agents

Patients receive recombinant interferon gamma subcutaneously weekly for 4 weeks before surgery.

Given subcutaneously weekly for four weeks prior to surgery.

Recombinant Interferon Gamma

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.

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.

100 mcg/m2 weekly injection for four weeks

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

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.

To determine whether systemic administration of IFNg will increase class II MHC expression in SS and MRCL tumors.

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.

Horizon Pharma USA, Inc.

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

Basic Science (Interferon Gamma and MHC Expression)

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Early termination of trial due to collection of enough data necessary to complete analysis.

Seth Pollack, MD

Pre-treatment

Post-treatment

Change in Class I Major Histocompatibility Complex (MHC) Expression After Treatment With IFN Gamma

MHC Class II Expression

Changes in Immune Response

Patients receive recombinant interferon gamma SC weekly for 4 weeks before surgery.

Laboratory Biomarker Analysis: Correlative studies

Recombinant Interferon Gamma: Given Subcutaneously

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Immune Changes Following Trabectedin in Patients With Metastatic or Unresectable Sarcoma	NCT03397186	Myxoid Liposarc... Round Cell Lipo... Stage III Soft ... Stage IV Soft T... Metastatic Soft... Unresectable So...	Biopsy Laboratory Biom... Trabectedin	18 Years -	Fred Hutchinson Cancer Center
Recombinant Interferon Gamma in Treating Patients With Soft Tissue Sarcoma	NCT01957709	Myxoid Liposarc... Round Cell Lipo... Synovial Sarcom...	Laboratory Biom... Recombinant Int...	18 Years -	Fred Hutchinson Cancer Center

Spots Global Cancer Trial Database for round cell liposarcoma