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

Study Overview
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Brief Summary
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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

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

Conditions
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Metastatic Breast Cancer in Germline-PALB2 Mutations Carriers

Intervention / Treatment
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* Drug: Niraparib


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Two-stage optimal Simon design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Niraparib<br>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 | Drug: Niraparib<br>* Niraparib, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Time from inclusion to progression or death (all-cause) or last follow-up whichever occurs first | 12 months | 
| Overall survival | Time from inclusion to death (all-cause) or last follow-up whichever occurs first | 12 months | 
| Tumoral response | Partial Response or Complete Response or Stable Disease, as per to RECIST 1.1 criteria for tumoral response, based on CT-Scan | 12 months | 
| 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 | 12 months | 
| Adverse event rate | Adverse events (clinical and biological) between inclusion and 72 months | 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 | 12 months |