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

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Breast Cancer in Germline-PALB2 Mutations Carriers
• Intervention / Treatment: Drug: Niraparib

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Odile Cohen Haguenauer, MD PhD; Phone Number: + 33 1 42 49 47 98; Email: odile.cohen-haguenauer@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2022
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): May 1, 2030

Study Registration Dates

• First Submitted: January 28, 2022
• First Submitted That Met QC Criteria: January 28, 2022
• First Posted (Actual): February 9, 2022

Study Record Updates

• Last Update Posted (Actual): March 8, 2022
• Last Update Submitted That Met QC Criteria: February 21, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Niraparib
• Other Study ID Numbers: P170929J

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No