Study Evaluating DNA Double-strand Breaks (DSBs) REpair Factors (POLQ, Shieldin Complex and 53BP1) Expression as Biomarker of PARP Inhibitor Resistance in Patients With Deleterious Germline Mutation in BRCA 1/2 and HER2-negative, Metastatic or Locally Advanced Breast Cancer. (REPARP)

February 26, 2024 updated by: Institut Claudius Regaud

Prospective and Multicentric Study Evaluating DNA Double-strand Breaks (DSBs) REpair Factors (POLQ, Shieldin Complex and 53BP1) Expression as Biomarker of PARP Inhibitor Resistance in Patients With Deleterious Germline Mutation in BRCA 1/2 and HER2-negative, Metastatic or Locally Advanced Breast Cancer.

The purpose of this study is to assess whether expression of not only POLQ/Polθ, but also Shieldin complex and/or 53BP1 are correlated with primary and/or acquired resistance to PARPi (Poly(ADP-Ribose) Polymerases inhibitors) in a sub-population of locally advanced or metastatic breast cancer patients and vary regarding type and location of gBRCA1/2 mutations.

This translational research program is composed of two multicentric, non-randomized prospective studies in patients with HER2-negative locally advanced or metastatic breast cancer:

  • The main study concerns 80 patients eligible for PARPi (according to the investigators).PARPi treatments (talazoparib or olaparib) will be administered and dosed according to the standard of care administration.
  • The sub-study concerns 40 patients in progression disease under PARPi alone.

For each included patient in the main study or sub-study, tumor biopsy specimen and blood samples will be collected at different times during the study.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Bordeaux, France
      • Caen, France
      • Clermont-Ferrand, France
      • Dijon, France
        • Not yet recruiting
        • Centre Georges Francois Leclerc
        • Contact:
      • La Roche-sur-Yon, France
        • Recruiting
        • Centre Hospitalier Départemental Vendée
        • Contact:
      • Lille, France
        • Recruiting
        • Centre Oscar Lambret
        • Contact:
      • Limoges, France
      • Lyon, France
      • Marseille, France
      • Montpellier, France
        • Recruiting
        • Centre de Cancérologie du Grand Montpellier
        • Contact:
      • Montpellier, France
      • Nîmes, France
      • Paris, France
        • Recruiting
        • Hopital Saint Louis
        • Contact:
      • Paris, France
        • Not yet recruiting
        • Institut Curie - Site de Paris
        • Contact:
      • Paris, France
      • Paris, France
      • Plérin, France
        • Not yet recruiting
        • CENTRE ARMORICAIN DE RADIOTHERAPIE, IMAGERIE MEDICALE ET ONCOLOGIE - Hôpital privé des Côtes d'Armor
        • Contact:
      • Poitiers, France
      • Rennes, France
      • Saint-Herblain, France
      • Saint-Étienne, France
      • Toulouse, France
      • Tours, France
        • Recruiting
        • Chru De Tours
        • Contact:
      • Vandoeuvre-les-nancy, France
      • Villejuif, France

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

MAIN STUDY

INCLUSION CRITERIA:

  1. Women (or men) aged ≥ 18 years with histologically proven breast cancer
  2. Metastatic relapse or locally advanced breast cancer
  3. No-HER2 overexpression or amplification
  4. Triple-negative (defines as ER<1%, PR<1% and HER2-negative as per ASCO CAP guidelines) or hormone receptor positive (defines as ER and/or PR ≥ 1%) breast cancer
  5. Patients with metastases that can be biopsied except bone metastases. At baseline, if patients already have an archived biopsy from a secondary or a primary site (if stage IV) of their current disease, this material can be used for the study, provided that, it was collected within 3 months prior enrollment and a frozen and a FFPE sample are both available for research
  6. ECOG Performance Status ≤ 2
  7. Patients must have measurable or evaluable disease according to RECIST v1.1
  8. Patient with deleterious germline BRCA 1 and/or 2 mutation, eligible for PARP inhibitor therapy (olaparib or talazoparib), according each investigator
  9. Any number of prior lines therapy are allowed
  10. Current treatment with PARP inhibitor not yet started
  11. Women should be post-menopaused or willing to accept the use of an effective contraceptive regimen during the treatment period by PARP inhibitor
  12. Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol
  13. Patient affiliated to a Social Health Insurance in France

NON-INCLUSION CRITERIA:

  1. Abnormal coagulation contraindicating biopsy
  2. Bone metastases when this is the only site of biopsiable disease
  3. Patients with all target in a previously irradiated region, except if clear progression has been observed prior to study in at least one of them
  4. Patients with known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
  5. Patients with known untreated CNS metastases and/or carcinomatous meningitis
  6. Patients with a known history of Human Immunodeficiency Virus (HIV)
  7. Patients with known active Hepatitis B or C
  8. Patients should not be on any other anti-cancer therapy (chemotherapy, endocrine therapy, immunotherapy, tailored therapy or alternative investigational therapy)
  9. Patient pregnant, or breast-feeding
  10. Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure
  11. Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice)

SUB-STUDY

INCLUSION CRITERIA:

  1. Women (or men) aged ≥ 18 years with histologically proven breast cancer
  2. Metastatic relapse or locally advanced breast cancer
  3. No-HER2 overexpression or amplification
  4. Triple-negative (defines as ER<1%, PR<1% and HER2-negative as per ASCO CAP guidelines) or hormone receptor positive (defines as ER and or PR ≥ 1%) breast cancer
  5. Patients with metastases that can be biopsied except bone metastases
  6. ECOG Performance Status ≤ 2
  7. Patients, with deleterious germline BRCA 1 and/or 2, in progression under PARPi alone (talazoparib or olaparib)
  8. Patient able to participate and willing to give informed consent prior performance of any study-related procedures and to comply with the study protocol
  9. Patient affiliated to a Social Health Insurance in France

NON-INCLUSION CRITERIA:

  1. Abnormal coagulation contraindicating biopsy
  2. Bone metastases when this is the only site of biopsiable disease
  3. Patient pregnant, or breast-feeding
  4. Patients with a known history of Human Immunodeficiency Virus (HIV)
  5. Patients with known active Hepatitis B or C
  6. Any psychological, familial, geographic or social situation, according to the judgment of investigator, potentially preventing the provision of informed consent or compliance to study procedure
  7. Patients already participating in the main REPARP study
  8. Patient who has forfeited his/her freedom by administrative or legal award or who is under legal protection (curatorship and guardianship, protection of justice)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Patients with breast cancer
Patients With Deleterious Germline Mutation in BRCA 1/2 and HER2-negative, Metastatic or Locally Advanced Breast Cancer.
Other: Main study:

For each included patient, tumor biopsy specimen and blood samples will be collected at baseline visit (before the first dose of PARPi treatment).

During the treatment period: blood samples will be scheduled every 8 weeks (i.e. 2 cycles).

At the time of progression: tumor biopsy and blood samples will be collected.

Other: Sub-study:
For each included patient, tumor biopsy specimen and blood samples will be collected as soon as possible after progression (before initiation of the post PARPi anti-tumoral treatment).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Main study: the primary endpoint is the Area under the Receiver Operating Characteristic Curve (ROC Curve) of POLQ expression to identify patients presenting progressive disease or death at 6 months under PARPi alone (primary resistance).
Time Frame: 6 months for each patient
Progression will be determined using RECIST v1.1 criteria.
6 months for each patient
Sub-study: the primary end point is the rate of patients presenting loss of Shieldin complex and/or 53BP1.
Time Frame: 1 month for each patient
1 month for each patient

Secondary Outcome Measures

Outcome Measure
Time Frame
Main study: Progression-Free Survival defined as the time from inclusion until progression according to RECIST v1.1 criteria or death from any cause, whichever occurs first.
Time Frame: 12 months for each patient
12 months for each patient
Main study: Objective Response (i.e. complete or partial response) defined using RECIST v1.1 criteria.
Time Frame: 12 months for each patient
12 months for each patient
Main study: Duration Of Response defined as the time from initial objective response until progression according to RECIST v1.1 criteria or death from any cause.
Time Frame: 12 months for each patient
12 months for each patient
Sub-study: expression of the Shieldin complex and 53BP1.
Time Frame: 1 month for each patient
1 month for each patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Claudius Regaud

Collaborators

Artios Pharma Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 23, 2022

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

June 1, 2025

Study Registration Dates

First Submitted

May 11, 2022

First Submitted That Met QC Criteria

May 17, 2022

First Posted (Actual)

May 18, 2022

Study Record Updates

Last Update Posted (Estimated)

February 28, 2024

Last Update Submitted That Met QC Criteria

February 26, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21 SEIN 09

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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