Immune Changes Following Trabectedin in Patients With Metastatic or Unresectable Sarcoma

NCT03397186 | Withdrawn Phase 2 FDA Drug

• 4 other identifiers: 9769NCI-2017-02298P30CA015704RG9217026
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myxoid Liposarcoma; Round Cell Liposarcoma; Stage III Soft Tissue Sarcoma AJCC v7; Stage IV Soft Tissue Sarcoma AJCC v7; Metastatic Soft Tissue Sarcoma; Unresectable Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• Percentage change of T cells (CD3+) by flow cytometry

  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.

  Baseline up to 4 weeks

Secondary Outcomes (4)

• Expression of inhibitory ligands including PD-1, CTLA-4, LAG-3 on infiltrating T cells

  Up to 4 weeks

• CD8+ or CD4+ phenotype of infiltrating T cells

  Up to 4 weeks

• Type 1 helper cell (Th1) versus (vs.) type 2 helper cell (Th2) phenotype of infiltrating T cells based on expression of CCR5 and CXCR3

  Up to 4 weeks

• Infiltrating tumor associated macrophage number

  Up to 4 weeks

Study Arms (1)

Basic science (trabectedin, biopsy)

OTHER

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.

Procedure: Biopsy; Other: Laboratory Biomarker Analysis; Drug: Trabectedin

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: Bx

Basic science (trabectedin, biopsy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Basic science (trabectedin, biopsy)

Trabectedin DRUG

Given as standard of care

Also known as: Ecteinascidin, ecteinascidin 743, ET-743, Yondelis

Basic science (trabectedin, biopsy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have a diagnosis of advanced (unresectable or metastatic) sarcoma, for which trabectedin treatment is indicated
• Subjects must have received prior anthracycline treatment; subjects who failed to tolerate it or for whom it is not clinically appropriate in the opinion of their treating physician may be included
• All ongoing toxicities related to prior therapy must be resolved to grade 1 or better (except alopecia)
• Total bilirubin level =\< upper limit of normal (ULN) mg/dL
• Aspartate aminotransferase (AST) =\< 2.5 x ULN
• Alanine aminotransferase (ALT) =\< 2.5 x ULN
• Alkaline phosphatase \< 2.5 x ULN
• Serum creatinine =\< 1.5 x ULN
• Calculated creatinine clearance \>= 30 mL/min using the Cockcroft-Gault formula may be included
• Creatine phosphokinase (CPK) =\< 2.5 x ULN
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Platelet count \>= 100 x 10\^9/L
• Hemoglobin \>= 9 g/dL
• Baseline left ventricular ejection fraction (LVEF) 45% or greater (by echocardiogram or multigated acquisition scan \[MUGA\] study) and no evidence of New York Heart Association class ll to IV heart failure
• Subjects with lesions safely accessible for biopsy, in the opinion of the treating physician and/or interventional radiology

You may not qualify if:

• Subjects for whom treatment with trabectedin is not indicated
• All subjects with brain metastases, except those meeting the following criteria:
• Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrollment
• No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
• Subjects must be either off steroids or on a stable or decreasing dose of =\< 10 mg daily prednisone (or equivalent), excluding dexamethasone given as pre-treatment for trabectedin
• Prior organ transplantation, including allogeneic stem cell transplantation
• Subjects with abnormal prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) or bleeding diathesis
• Prior treatment with trabectedin
• Prior chemotherapy within 2 weeks; prior immunotherapy or biologic therapy within 4 weeks; prior radiation therapy within 3 weeks
• Significant acute or chronic infections as these may affect the immune response including:
• Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Positive test for hepatitis B virus (HBV) surface antigen and / or confirmatory hepatitis C virus (HCV) ribonucleic acid (RNA) (if anti-HCV antibody tested positive)
• Subjects on chronic therapy with any systemic immunosuppressant (not counting inhaled steroids or steroid creams) for any reason, including autoimmune disease
• Known alcohol or drug abuse
• Subjects who are breast feeding

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Janssen Pharmaceuticals: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Liposarcoma, Myxoid; Sarcoma

Interventions

Biopsy; Trabectedin

Condition Hierarchy (Ancestors)

Liposarcoma; Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Seth Pollack

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2018
• First Posted: January 11, 2018
• Study Start: June 19, 2018
• Primary Completion: January 1, 2021
• Study Completion: May 1, 2021
• Last Updated: September 10, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)