PALB2-PARPi-01: PARP-inhibitor on Advanced Metastatic Breast Cancer in Germline PALB2 Mutations Carriers
Study Details
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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 |
Drug: Niraparib
Niraparib, once daily
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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
Eligibility Criteria
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)
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Assistance Publique - Hôpitaux de Paris
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- P170929J