Overview

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

Status:
Suspended
Trial end date:
2023-08-01
Target enrollment:
0
Participant gender:
All
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
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
The Netherlands Cancer Institute
Collaborator:
Tesaro, Inc.
Treatments:
Niraparib
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.