Prospective Identification of Predictive Biomarkers of Trabectedin Efficacy in Non-L Soft-tissue Sarcoma Patients (PIPER)
Primary Purpose
Soft Tissue Sarcoma Adult, Undifferentiated Pleomorphic Sarcoma, Epithelioid Sarcoma
Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Trabectedin
Sponsored by
About this trial
This is an interventional screening trial for Soft Tissue Sarcoma Adult focused on measuring Soft-tissue sarcoma, Predictive biomarkers, Next-generation sequencing
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years,
- 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),
- Locally advanced/unresectable and/or metastatic disease,
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Appendix 1),
- Measurable disease according to RECIST v1.1,
- Indication of trabectedin according to market authorization,
- At least one target lesion that can be biopsied for research,
- Women of childbearing potential must have a negative serum pregnancy test before study entry,
- Patient with a social security in compliance with the French law,
- Voluntary signed and dated written informed consent prior to any study specific procedure,
- 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:
- Previous treatment with trabectedin,
- Known hypersensitivity to any of its components,
- Patients with an active serious or uncontrolled infection upon investigator judgement,
- Radiological evidence of symptomatic or progressive brain metastases,
- Abnormal coagulation contraindicating biopsy,
- Any medical and/or biological contra-indication to treatment by trabectedin as per market authorization specification (as per investigator judgement),
- Patients unable to receive corticotherapy,
- 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,
- Evidence of severe or uncontrolled systemic disease (uncontrolled hypertension, active bleeding diatheses, or active Hepatitis B, C and HIV),
- 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,
- Individuals deprived of liberty or placed under guardianship,
- Pregnant or breast feeding women,
- Previous enrolment in the present study.
Sites / Locations
- Institut BergonieRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Biomarker analysis
Arm Description
This study is a single arm study with biomarker analysis
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Safety profile of trabectedin: Common Terminology Criteria for Adverse Events version 5
Toxicity graded using the Common Terminology Criteria for Adverse Events version 5.
Safety profile of biopsy: Common Terminology Criteria for Adverse Events version 5
Toxicity graded using the Common Terminology Criteria for Adverse Events version 5.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04008238
Brief Title
Prospective Identification of Predictive Biomarkers of Trabectedin Efficacy in Non-L Soft-tissue Sarcoma Patients
Acronym
PIPER
Official Title
Prospective Identification of Predictive Biomarkers of Trabectedin Efficacy in Non-L Soft-tissue Sarcoma Patients
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 6, 2020 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Bergonié
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Soft Tissue Sarcoma Adult, Undifferentiated Pleomorphic Sarcoma, Epithelioid Sarcoma, Solitary Fibrous Tumors, Hemangioendothelioma, Desmoplastic Round Cell Tumor, Synovial Sarcoma
Keywords
Soft-tissue sarcoma, Predictive biomarkers, Next-generation sequencing
7. Study Design
Primary Purpose
Screening
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
200 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Biomarker analysis
Arm Type
Experimental
Arm Description
This study is a single arm study with biomarker analysis
Intervention Type
Drug
Intervention Name(s)
Trabectedin
Intervention Description
- 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
Primary Outcome Measure Information:
Title
Efficacy of trabectedin: objective response [OR] or stable disease [SD] > 6 months
Description
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.
Time Frame
Throughout the treatment period, an expected average of 6 months
Secondary Outcome Measure Information:
Title
Safety profile of trabectedin: Common Terminology Criteria for Adverse Events version 5
Description
Toxicity graded using the Common Terminology Criteria for Adverse Events version 5.
Time Frame
Throughout the treatment period, an expected average of 6 months
Title
Safety profile of biopsy: Common Terminology Criteria for Adverse Events version 5
Description
Toxicity graded using the Common Terminology Criteria for Adverse Events version 5.
Time Frame
Throughout the treatment period, an expected average of 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years,
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),
Locally advanced/unresectable and/or metastatic disease,
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Appendix 1),
Measurable disease according to RECIST v1.1,
Indication of trabectedin according to market authorization,
At least one target lesion that can be biopsied for research,
Women of childbearing potential must have a negative serum pregnancy test before study entry,
Patient with a social security in compliance with the French law,
Voluntary signed and dated written informed consent prior to any study specific procedure,
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:
Previous treatment with trabectedin,
Known hypersensitivity to any of its components,
Patients with an active serious or uncontrolled infection upon investigator judgement,
Radiological evidence of symptomatic or progressive brain metastases,
Abnormal coagulation contraindicating biopsy,
Any medical and/or biological contra-indication to treatment by trabectedin as per market authorization specification (as per investigator judgement),
Patients unable to receive corticotherapy,
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,
Evidence of severe or uncontrolled systemic disease (uncontrolled hypertension, active bleeding diatheses, or active Hepatitis B, C and HIV),
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,
Individuals deprived of liberty or placed under guardianship,
Pregnant or breast feeding women,
Previous enrolment in the present study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Antoine ITALIANO, MD, PhD
Phone
+33 5.56.33.33.33
Email
a.italiano@bordeaux.unicancer.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Simone MATHOULIN-PELISSIER, MD, PhD
Email
s.mathoulin@bordeaux.unicancer.fr
Facility Information:
Facility Name
Institut Bergonie
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antoine ITALIANO, MD, PhD
Email
a.italiano@bordeaux.unicancer.fr
First Name & Middle Initial & Last Name & Degree
Antoine ITALIANO
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Prospective Identification of Predictive Biomarkers of Trabectedin Efficacy in Non-L Soft-tissue Sarcoma Patients
We'll reach out to this number within 24 hrs