This is an open-label, single-arm pilot study evaluating the antitumor activity and safety of
niraparib as neoadjuvant therapy in participants with Human epidermal growth factor receptor
2 (HER2)-negative and breast cancer susceptibility gene mutant (BRCAmut) localized breast
cancer (primary tumor >=1 centimeters [cm]). Breast magnetic resonance imaging (MRI), breast
ultrasound, and tumor core biopsy will be performed at the screening (Days -28 to -1).
Participants will receive niraparib (200 milligrams [mg] orally [PO]) treatment daily for 28
days (Cycle 1) and then will undergo breast ultrasound at the end of Cycle 1 on Day 28. Based
on breast ultrasound reports, the participants will either discontinue the study (disease
progression) or will continue niraparib treatment (complete response [CR], partial response
[PR] or stable disease [SD]) for an additional cycle (Cycle 2). A breast MRI and breast
ultrasound will be performed at the end of Cycle 2. Approximately 21 participants will be
enrolled in this study and the study duration will be approximately 2 years.
Inclusion Criteria:
- Participants age >= 18 years old.
- Participants with a deleterious or suspected deleterious breast cancer susceptibility
gene 1 (BRCA1) or BRCA2 mutation (germline or somatic) may be enrolled into the study
based on either local or central laboratory testing of BRCA status.
- Histologically-confirmed HER2-negative localized breast cancer by core biopsy.
- Primary operable, non-metastatic invasive carcinoma of the breast, confirmed
histologically by core biopsy. Fine-needle aspiration is not sufficient. Incisional
biopsy is not allowed. In participants with multifocal and/or multicentric, the
largest lesion should be measured. Both unilateral and bilateral breast cancer are
allowed.
- Primary tumor size >=1cm.
- Measurable disease by breast ultrasound and MRI.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate organ function defined as:
1. Absolute neutrophil count (ANC) >=1500 per microliters (/μL).
2. Platelets >=100,000/μL.
3. Hemoglobin >=9 grams per deciliter (g/dL).
4. Serum creatinine <=1.5*upper limit of normal (ULN) or calculated creatinine
clearance >=50 milliliters per minute (mL/min) using Cockcroft-Gault equation.
5. Total bilirubin <=1.5*ULN except in participants with Gilbert's syndrome.
Participants with Gilbert's syndrome may enroll if direct bilirubin <=1.5*ULN of
the direct bilirubin.
6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=2.5*ULN.
- Participants must have recovered to Grade 1 toxicity from prior cancer therapy (a
participant with Grade 2 neuropathy or Grade 2 alopecia is an exception to this
criterion and may qualify for this study).
- Participant able to take oral medications.
- Participant meets the following criteria:
1. Female participant (of childbearing potential) is not breastfeeding, has a
negative serum pregnancy test within 72 hours prior to taking study drug, and
agrees to abstain from activities that could result in pregnancy from Screening
through 180 days after the last dose of study drug, or is of non-childbearing
potential.
2. Female participant is of non-childbearing potential (other than medical reasons)
as defined:
i) >=45 years of age and has not had menses for >1 year. ii) Amenorrheic for <2 years
without a hysterectomy and oophorectomy and a follicle-stimulating hormone value in
the postmenopausal range upon the screening evaluation.
iii) Has undergone post hysterectomy, bilateral oophorectomy, or tubal ligation. Documented
hysterectomy, oophorectomy or tubal ligation must be confirmed in the medical records,
otherwise the participant must be willing to use 2 adequate barrier methods throughout the
study starting from the screening visit through 180 days after the last dose of study drug.
Information must be captured appropriately within the site's source documents.
c) Male participant agrees to use an effective method of contraception starting with the
first dose of study therapy through 120 days after the last dose of study therapy.
- Able to understand the study procedures and agree to participate in the study by
providing written informed consent.
Exclusion Criteria:
- Prior anti-cancer therapies for current malignancy.
- Known evidence of distant metastasis. Staging studies are not required. The decision
to pursue staging studies is at the discretion of the treating clinician, based on the
participant's clinical and pathological findings consistent with standard guidelines.
- Known hypersensitivity to the components of niraparib components or their formulation
excipients.
- Major surgery within 3 weeks of starting the study or participant has not recovered
from any effects of any major surgery.
- Poor medical risk due to a serious, uncontrolled medical disorder, non-malignant
systemic disease or active, uncontrolled infection. Examples include, but are not
limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial
infarction, uncontrolled major seizure disorder, unstable spinal cord compression,
superior vena cava syndrome, uncontrolled hypertension, active uncontrolled
coagulopathy, bleeding disorder, or any psychiatric disorder that prohibits obtaining
informed consent.
- History or current evidence of any condition, therapy, or laboratory abnormality that
might confound the results of the study, interfere with the participant's
participation for the full duration of the study drug, or is not in the best interest
of the participant to participate.
- Participant is pregnant or breastfeeding, or expecting to conceive children within the
projected duration of the study drug or within the 180-day period after the last dose
of study drug.
- Immunocompromised participants.
- Known active hepatic disease (Hepatitis B or C).
- Prior treatment with a known PARP inhibitor.
- Other active malignancy that warrants systemic therapy.
- Known history of myelodysplastic syndromes (MDS) or Acute myeloid leukemia (AML).
