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PARP-inhibitor on Advanced Metastatic Breast Cancer in Germline PALB2 Mutations Carriers (PALB2-PARPi-01)

Primary Purpose

Metastatic Breast Cancer in Germline-PALB2 Mutations Carriers

Status

Not yet recruiting

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Niraparib

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer in Germline-PALB2 Mutations Carriers

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adult patients over 18 years
PALB2 germline heterozygous mutation carrier, wild type BRCA1&2 (breast cancer 1&2) affected with metastatic breast cancer in first metastatic treatment line or beyond
Histologically or cytologically confirmed breast cancer with evidence of metastatic disease.
Triple Negative breast cancer; Patients affected with triple negative cancers should have received anthracyclines and taxanes in neo/adjuvant therapy.
Or patients with Hormonal receptor positive (HR+)/ Human epidermal growth factor receptor 2 negative (HER2-) breast cancer, with treatment failure after a second line of therapy; Estrogen Receptor/ProgesteroneReceptor breast cancer positive patients must have received and progressed on currently recommended therapies in this indication (endocrine therapy, CDK4/6 inhibitors (adjuvant or metastatic)), or have a disease form that the treating physician believes to be inappropriate for recommended therapies in this indication.
Prior therapy with an anthracycline and a taxane in an adjuvant setting.
Prior platinum allowed as long as no breast cancer progression occurred on treatment or if given in adjuvant/neoadjuvant setting, at least 12 months elapsed from last dose to study entry.
Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Adequate bone marrow, kidney and liver function.
Patients without visceral crisis

Exclusion Criteria:

Patients with HER2 positive disease.
Untreated and/or uncontrolled brain metastases.
Patients in visceral crisis requiring chemotherapy
Cytopenia, defined with the following thresholds: (i) Neutrophil count < 1500/mm3; Platelet count< 100 000/mm3; Hemoglobin <9g/dL
Prior malignancy unless curatively treated and disease-free for > 5 years prior to study entry. Prior adequately treated non-melanoma skin cancer, in situ cancer of the cervix, ductal carcinoma in situ (DCIS) or stage I grade 1 endometrial cancer allowed.
Known HIV (Human Immunodeficiency Virus) infection.
Pregnant or breast-feeding women.
Lack of affiliation to a social security benefit plan (as a beneficiary or assignee)

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Niraparib

Arm Description

PARP-inhibitor, Niraparib Dosage : starting 300 mg/day for patients with body weight ≥77kg and platelet counts ≥ 150 000/µl or 200 mg when body weight inferior to 77kg and/or platelet counts ≤ 150 000/µl and > 100 000/µl Pharmaceutical form : 100 mg capsules Posology : single dose daily Route of administration : oral Administration procedures : oral, daily single dose Duration of treatment : 12 cycles of 28 days each

Outcomes

Primary Outcome Measures

Objective response rate

Complete or partial tumour response according to RECIST 1.1 criteria accounting for objective response rate in solid tumours at 4 cycles., based on the CT-Scan

Secondary Outcome Measures

Progression-free survival

Time from inclusion to progression or death (all-cause) or last follow-up whichever occurs first

Overall survival

Time from inclusion to death (all-cause) or last follow-up whichever occurs first

Tumoral response

Partial Response or Complete Response or Stable Disease, as per to RECIST 1.1 criteria for tumoral response, based on CT-Scan

Duration of response

Time to treatment failure, defined as time between inclusion and treatment discontinuation (any reason: death, disease progression, toxicity) or last follow-up

Adverse event rate

Adverse events (clinical and biological) between inclusion and 72 months

Quality of Life variation

European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life C30 Questionnaire, evaluated every 3 months, from inclusion to 12 month

Full Information

NCT ID

NCT05232006

First Posted

January 28, 2022

Last Updated

February 21, 2022

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT05232006

Brief Title

PARP-inhibitor on Advanced Metastatic Breast Cancer in Germline PALB2 Mutations Carriers

Acronym

PALB2-PARPi-01

Official Title

Phase II Clinical Trial Aiming at Investigating the Effect of a PARP-inhibitor on Advanced Metastatic Breast Cancer in Germline PALB2 Mutations Carriers

Study Type

Interventional

2. Study Status

Record Verification Date

January 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

May 2022 (Anticipated)

Primary Completion Date

September 2024 (Anticipated)

Study Completion Date

May 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The study aims at exploring the potential benefit of a PARP-inhibitor, Niraparib, in metastatic breast cancer developing in germline-PALB2 mutations carriers. This study is designed as a multicentre one-arm two-stage phase 2 clinical trial

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Breast Cancer in Germline-PALB2 Mutations Carriers

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

Two-stage optimal Simon design

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Niraparib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Niraparib

Intervention Description

Niraparib, once daily

Primary Outcome Measure Information:

Title

Objective response rate

Description

Complete or partial tumour response according to RECIST 1.1 criteria accounting for objective response rate in solid tumours at 4 cycles., based on the CT-Scan

Time Frame

4 months

Secondary Outcome Measure Information:

Title

Progression-free survival

Description

Time from inclusion to progression or death (all-cause) or last follow-up whichever occurs first

Time Frame

12 months

Title

Overall survival

Description

Time from inclusion to death (all-cause) or last follow-up whichever occurs first

Time Frame

12 months

Title

Tumoral response

Description

Partial Response or Complete Response or Stable Disease, as per to RECIST 1.1 criteria for tumoral response, based on CT-Scan

Time Frame

12 months

Title

Duration of response

Description

Time to treatment failure, defined as time between inclusion and treatment discontinuation (any reason: death, disease progression, toxicity) or last follow-up

Time Frame

12 months

Title

Adverse event rate

Description

Adverse events (clinical and biological) between inclusion and 72 months

Time Frame

72 months

Title

Quality of Life variation

Description

European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life C30 Questionnaire, evaluated every 3 months, from inclusion to 12 month

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult patients over 18 years PALB2 germline heterozygous mutation carrier, wild type BRCA1&2 (breast cancer 1&2) affected with metastatic breast cancer in first metastatic treatment line or beyond Histologically or cytologically confirmed breast cancer with evidence of metastatic disease. Triple Negative breast cancer; Patients affected with triple negative cancers should have received anthracyclines and taxanes in neo/adjuvant therapy. Or patients with Hormonal receptor positive (HR+)/ Human epidermal growth factor receptor 2 negative (HER2-) breast cancer, with treatment failure after a second line of therapy; Estrogen Receptor/ProgesteroneReceptor breast cancer positive patients must have received and progressed on currently recommended therapies in this indication (endocrine therapy, CDK4/6 inhibitors (adjuvant or metastatic)), or have a disease form that the treating physician believes to be inappropriate for recommended therapies in this indication. Prior therapy with an anthracycline and a taxane in an adjuvant setting. Prior platinum allowed as long as no breast cancer progression occurred on treatment or if given in adjuvant/neoadjuvant setting, at least 12 months elapsed from last dose to study entry. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Adequate bone marrow, kidney and liver function. Patients without visceral crisis Exclusion Criteria: Patients with HER2 positive disease. Untreated and/or uncontrolled brain metastases. Patients in visceral crisis requiring chemotherapy Cytopenia, defined with the following thresholds: (i) Neutrophil count < 1500/mm3; Platelet count< 100 000/mm3; Hemoglobin <9g/dL Prior malignancy unless curatively treated and disease-free for > 5 years prior to study entry. Prior adequately treated non-melanoma skin cancer, in situ cancer of the cervix, ductal carcinoma in situ (DCIS) or stage I grade 1 endometrial cancer allowed. Known HIV (Human Immunodeficiency Virus) infection. Pregnant or breast-feeding women. Lack of affiliation to a social security benefit plan (as a beneficiary or assignee)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Odile Cohen Haguenauer, MD PhD

Phone

+ 33 1 42 49 47 98

odile.cohen-haguenauer@aphp.fr

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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PARP-inhibitor on Advanced Metastatic Breast Cancer in Germline PALB2 Mutations Carriers

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