Clinical Trials /

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

NCT02826512

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Feasibility Study of Niraparib for Advanced, BRCA1-like, HER2-negative Breast Cancer Patients
  • Official Title: A Feasibility Study of Niraparib for Advanced, BRCA1-like, HER2-negative Breast Cancer Patients: the ABC Study

Clinical Trial IDs

  • ORG STUDY ID: M14ABC
  • NCT ID: NCT02826512

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
NiraparibNiraparib

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
NiraparibExperimentalniraparib 300 mg QD continuously
  • Niraparib

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;

          -  Symptomatic brain metastases or leptomeningeal metastases. If adequately treated with
             resection and/or irradiation and patients are at least four weeks completely free of
             symptoms of these metastases and without medication related to these metastases
             (steroids are allowed) patients could be eligible if all other in- and exclusion
             criteria are obeyed;

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:From date of randomization until date of first documented progression or date of death, whichever comes first, assessed up to 120 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective response rate
Time Frame:Assessed up to 120 months
Safety Issue:
Description:
Measure:Duration of response
Time Frame:Assessed up to 120 months
Safety Issue:
Description:Time from date of response to progression of disease
Measure:Toxicity; Incidence of toxicity, graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 4.03
Time Frame:up to 30 days after end of treatment
Safety Issue:
Description:Adverse events will be graded according to NCI Common Toxicity Criteria version 4.03

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:The Netherlands Cancer Institute

Trial Keywords

  • BRCA1-like
  • HER2 negative

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