Prospective Identification of Predictive Biomarkers of Trabectedin Efficacy in Non-L Soft-tissue Sarcoma Patients (PIPER)

This is a biology driven, monocentric study, designed to identify biomarkers of activity of trabectedin in patients with advanced non-L soft-tissue sarcoma. The aim of this study is to implement high-throughput profiling technologies to identify predictive biomarkers of trabectedin efficacy through sequential tumor biopsies and blood sample collection in sarcoma patients.

Study Overview

• Status: Completed
• Conditions: Soft Tissue Sarcoma Adult; Solitary Fibrous Tumors; Hemangioendothelioma; Synovial Sarcoma; Undifferentiated Pleomorphic Sarcoma; Epithelioid Sarcoma; Desmoplastic Round Cell Tumor
• Intervention / Treatment: Drug: Trabectedin

Detailed Description

The identification of predictive biomarkers of the clinical benefit of trabectedin is a crucial issue to identify potential responders particularly for non-L sarcomas. Considering that the molecular profile of STS can change over time, an analysis of archival tumor material may not be a reliable method to identify predictive biomarkers of response, and thus high-throughput technologies may be promising to identify STS markers for prediction of response to trabectedin. For study purpose, blood and tumor samples will be obtained for genetic and immunological profiling at baseline, during treatment by trabectedin and at disease progression.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33076
    • Institut Bergonie

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18 years,
2. Histology: undifferentiated pleomorphic sarcomas, epithelioid sarcomas, solitary fibrous tumors, hemangioendothelioma, desmoplastic round cell tumors, synovial sarcomas or other non-leiomyosarcoma/non-liposarcoma softtissue sarcoma. As per the Frech NCI recommendation, diagnosis must be reviewed or confirmed by the RRePS Network (Réseau de Référence en Pathologie des Sarcomes des tissus mous et des Viscères),
3. Locally advanced/unresectable and/or metastatic disease,
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Appendix 1),
5. Measurable disease according to RECIST v1.1,
6. Indication of trabectedin according to market authorization,
7. At least one target lesion that can be biopsied for research,
8. Women of childbearing potential must have a negative serum pregnancy test before study entry,
9. Patient with a social security in compliance with the French law,
10. Voluntary signed and dated written informed consent prior to any study specific procedure,
11. Women must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of trabectedin. Men must agree to use a medically acceptable method of contraception throughout the treatment period and for 5 months after discontinuation of trabectedin. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >=1 year.

Exclusion Criteria:

1. Previous treatment with trabectedin,
2. Known hypersensitivity to any of its components,
3. Patients with an active serious or uncontrolled infection upon investigator judgement,
4. Radiological evidence of symptomatic or progressive brain metastases,
5. Abnormal coagulation contraindicating biopsy,
6. Any medical and/or biological contra-indication to treatment by trabectedin as per market authorization specification (as per investigator judgement),
7. Patients unable to receive corticotherapy,
8. Previous or current malignancies of other histologies within the last 2 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin and prostate cancer,
9. Evidence of severe or uncontrolled systemic disease (uncontrolled hypertension, active bleeding diatheses, or active Hepatitis B, C and HIV),
10. Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol,
11. Individuals deprived of liberty or placed under guardianship,
12. Pregnant or breast feeding women,
13. Previous enrolment in the present study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• 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: Biomarker analysis; This study is a single arm study with biomarker analysis	Drug: Trabectedin; - Trabectedin will be prescribed as per market authorization and will be administered by intraveinous infusion (1,5 mg/m²) every 3 weeks. A treatment cycle is defined as a 3-weeks period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of trabectedin: objective response [OR] or stable disease [SD] > 6 months	Efficacy of trabectedin is defined as objective response [OR] or stable disease [SD] > 6 months. Absence of efficacy is defined as progressive disease [PD] within 2 months.	Throughout the treatment period, an expected average of 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety profile of trabectedin: Common Terminology Criteria for Adverse Events version 5	Toxicity graded using the Common Terminology Criteria for Adverse Events version 5.	Throughout the treatment period, an expected average of 6 months
Safety profile of biopsy: Common Terminology Criteria for Adverse Events version 5	Toxicity graded using the Common Terminology Criteria for Adverse Events version 5.	Throughout the treatment period, an expected average of 6 months

Collaborators and Investigators

• Sponsor: Institut Bergonié

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2020
• Primary Completion (Actual): August 31, 2024
• Study Completion (Actual): August 31, 2024

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 3, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Soft-tissue sarcoma; Next-generation sequencing; Predictive biomarkers
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Neoplasms, Vascular Tissue; Neoplasms, Fibrous Tissue; Hemangioma; Histiocytoma; Sarcoma; Sarcoma, Synovial; Histiocytoma, Malignant Fibrous; Solitary Fibrous Tumors; Hemangioendothelioma; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dioxoles; Tetrahydroisoquinolines; Isoquinolines; Trabectedin
• Other Study ID Numbers: IB 2019-02; 2019-A02137-50 (Other Identifier: ID-RCB)

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: No
• Studies a U.S. FDA-regulated device product: No