A Feasibility Study of Niraparib for Advanced, BRCA1-like, HER2-negative Breast Cancer Patients

NCT ID: NCT02826512

Last Updated: 2022-07-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-15
• Study Completion Date: 2022-07-01

Brief Summary

Patients with locally recurrent BRCA1-like, HER2-negative breast cancer that cannot be treated with curative intent by local treatment (surgery, radiotherapy +/- hyperthermia) or patients with metastatic BRCA1-like, HER2-negative breast cancer that have received a maximum of one prior line of treatment for incurable disease will be treated with Niraparib until disease progression

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Niraparib

niraparib 300 mg QD continuously

Group Type: EXPERIMENTAL

Niraparib

Intervention Type: DRUG

niraparib 300 mg QD continuously

Interventions

Niraparib

niraparib 300 mg QD continuously

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histological proof of advanced, HER2 negative breast cancer;
• Fresh frozen primary tumor sample available or metastasis accessible for fresh frozen biopsy;
• The tumor must be BRCA1-like, as identified by Agendia's RNA-based BRCAness classifier;
• Only the following patients may be referred for BRCA1-like testing: all patients that had triple negative primary breast cancer; hormone-receptor positive, HER2-negative primary breast cancer patients with a histological grade III breast cancer; Breast cancer patients carrying a BRCA1 and/or BRCA2 germ line mutation.
• Pretreatment containing an anthracycline and/or taxane in the (neo-)adjuvant or metastatic setting received, or if not, then discussed with the patient whether it is justified to forego these treatments;
• Maximum of one prior line of chemotherapy for advanced disease.
• Age ≥ 18 years;
• Able and willing to give written informed consent;
• WHO performance status of 0, 1 or 2;
• Life expectancy ≥ 3 months, allowing adequate follow up of toxicity evaluation and antitumor activity;
• Measurable or evaluable disease according to RECIST 1.1 criteria;
• Minimal acceptable safety laboratory values

• ANC of ≥ 1.5 x 109 /L
• Platelet count of ≥ 150 x 109 /L
• Hemoglobin ≥ 10 g/dL (6.21mmol/L)
• Hepatic function as defined by total serum bilirubin ≤ 1. 5 x ULN (except elevated bilirubin due to Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin), ASAT and ALAT < 2.5 x ULN or <5 x ULN in case of liver metastasis
• Renal function as defined by serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min (by Cockcroft-Gault formula);
• Negative pregnancy test (urine/serum) for female patients with childbearing potential.

Exclusion Criteria

• Any treatment with investigational drugs within 28 days prior to receiving the first dose of investigational treatment; or within 21 days for standard chemotherapy; or within 14 days for weekly scheduled chemotherapeutic regimens or endocrine therapy;
• Patients who have progressed on previous palliative treatment with PARP1-inhibitors, platinum compounds or high dose alkylating agents with autologous stem cell rescue, since preclinical and anecdotal clinical data in breast cancer indicate that these cancers have acquired resistance to PARP-inhibitors based on genetic reversion, epigenetic modifications, or as yet unknown mechanisms. Platinum-sensitive or PARP1-inhibitor-sensitive patients who stopped for reasons other than progression are eligible;
• Patients who received high-dose alkylating agents with autologous stem cell rescue in the (neo)adjuvant setting, unless these treatments had been received longer than 3 years ago;
• Pretreatment not containing an anthracycline and/or taxane, either in the (neo-) adjuvant or metastatic setting unless these treatments are not indicated;
• Women who have a positive pregnancy test (urine/serum) and/or who are breast feeding;
• Unreliable contraceptive methods. Women and men enrolled in this trial must agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: oral, injected or implanted hormonal methods, intra-uterine devices or systems, condom or other barrier contraceptive measures, sterilization and true abstinence);
• Radiotherapy within the last four weeks prior to receiving the first dose of investigational treatment; except 1x8 Gray for pain palliation then a seven days interval should be maintained;
• Patients must not have any known history of myelodysplastic syndrome (MDS) or other cytogenetic abnormality associated with MDS
• Patients must not have known persistent (> 4 weeks) ≥ Grade 2 toxicity from prior cancer therapy (except for alopecia gr 2).
• Patients must not have known ≥ Grade 3 hematological toxicity with the last chemotherapy regimen
• Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients;
• Patients with an active hepatitis B or C;
• Recent myocardial infarction (< six months) or unstable angina;
• Any medical condition not yet specified above that is considered to possibly, probably or definitely interfere with study procedures, including adequate follow-up and compliance and/or would jeopardize safe treatment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tesaro, Inc.

INDUSTRY

Sponsor Role: collaborator

The Netherlands Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Antoni van Leeuwenhoek

Amsterdam, , Netherlands

Deventer ziekenhuis

Deventer, , Netherlands

Erasmus Medical Center Cancer Institute

Rotterdam, , Netherlands

Countries

Netherlands

Other Identifiers

M14ABC

Identifier Type: -

Identifier Source: org_study_id