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

Phase 2

Not yet recruiting

• Conditions: Metastatic Breast Cancer in Germline-PALB2 Mutations Carriers
• Interventions: Drug: Niraparib

• Registration Number: NCT05232006
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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

Detailed Description

Not available

Study Timeline

• Status Verified: 2022-01
• Study First Submitted: 2022-01-28
• Study First Submitted QC: 2022-01-28
• Study First Posted: 2022-02-09
• Last Update Submitted: 2022-02-21
• Last Update Posted: 2022-03-08
• Study Start: 2022-05
• Primary Completion: 2024-09
• Study Completion: 2030-05

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 12

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Niraparib	Niraparib	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

Primary Outcome Measures

Name	Time	Method
Objective response rate	4 months	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

Name	Time	Method
Quality of Life variation	12 months	European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life C30 Questionnaire, evaluated every 3 months, from inclusion to 12 month
Progression-free survival	12 months	Time from inclusion to progression or death (all-cause) or last follow-up whichever occurs first
Overall survival	12 months	Time from inclusion to death (all-cause) or last follow-up whichever occurs first
Tumoral response	12 months	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	12 months	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	72 months	Adverse events (clinical and biological) between inclusion and 72 months