| Eligibility |
Inclusion Criteria:
- 1. Patients have been informed about the nature of study, including the exploratory
sub-study and has agreed to participate and signed the informed consent prior to
participation in any study related activities.
- 2. Male or female patients = 18 years of age.
- 3. Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1 which
the Investigator believes is stable at the time of screening.
- 4. Life expectancy =16 weeks.
- 5. Patients have a histologically and/or cytologically confirmed diagnosis of breast
cancer.
- 6. Patients have radiologic evidence of inoperable locally recurrent or metastatic
breast cancer (MBC) that are not candidates for curative intent.
- 7. Patients have human epidermal growth factor receptor 2 (HER2)- negative breast
cancer (based on most recently analyzed biopsy) defined as a negative in situ
hybridization (ISH) test or an immunohistochemistry (IHC) status of 0, 1+, or 2+ (if
IHC 2+, a negative ISH test is required) by local laboratory testing.
- 8. Patients have hormone receptor (HR)-positive breast cancer (based on most recently
analyzed biopsy) defined as estrogen receptor (ER) and/or progesterone receptor (PgR)
with =10% of tumor cells positive for ER and/or PgR by IHC irrespective of staining
intensity.
- 9. [Cohort A]: Patients with documented germinal mutation in BRCA1 or BRCA2 genes that
is predicted to be deleterious or suspected deleterious (known or predicted to be
detrimental/lead to loss of function). Patients with germinal mutations in BRCA1 or
BRCA2 genes (gBRCAms) that are considered to be nondetrimental (e.g., "Variants of
uncertain clinical significance" or "Variant of unknown significance" or "Variant,
favor polymorphism" or "benign polymorphism," etc.) will not be eligible for the
study. Germinal BRCA1/2 results preceding the ICF signature will be accepted, as long
as the results are documented and captured in the medical record during the
pre-screening period.
- 10. [Exploratory cohort B]: : Patients with either germinal BRCA1/2 wild-type
(gBRCAwt) or gBRCAms that are considered to be nondetrimental (e.g., "Variants of
uncertain clinical significance" or "Variant of unknown significance" or "Variant,
favor polymorphism" or "benign polymorphism," etc.) and homologous recombination
deficiency (HRD) based on the Myriad myChoice® CDx PLUS test. HRD status will be
centrally confirmed both on the most recent tumor tissue since last progression (from
either metastasis or primary tumor) and blood samples. Patients with a Myriad
myChoice® CDx PLUS score of = 25 or greater will be considered to have an abnormal HRR
pathway and defined as HRD.
- 11. [Exploratory cohort B]: Willingness and ability to provide additional six
formalin-fixed paraffin-embedded (FFPE) tissue slides from the most recent tumor
tissue since last progression (from either metastasis or primary tumor) to centrally
perform the assay. It is strongly recommended obtaining six consecutive sections from
the same tissue block used for the determination of HRD status.
- 12. At least one and up to two prior lines of endocrine therapy (aromatase inhibitors
[AIs] or fulvestrant) for treatment of locally recurrent and/or metastatic disease
(except for patients progressing in the neoadjuvant or adjuvant setting).
- 13. Confirmed disease progression while in the last AI-containing regimen (not
necessarily in the treatment line immediately prior to study entry) with secondary
endocrine resistance criteria.
- 14. Patients may have progressed on no more than one chemotherapy regimens in the
metastatic setting.
- 15. The following will not be counted as a prior line of cytotoxic chemotherapy:
- Prior hormonal therapy and non-hormonal targeted therapy.
- Targeted and biologic therapies.
- The patient can receive a stable dose of bisphosphonates or denosumab for bone
metastases, before and during the study as long as this was started at least 5
days prior to study treatment.
- 16. Prior carboplatin- or other platinum compound-based therapy is allowed if have
been administered in one of the following settings:
- Disease-free interval > 12 months from date of completion of neoadjuvant or
adjuvant treatment.
- As potentially curative treatment for a prior non-breast cancer with no evidence
of disease for = 5 years.
- 17. Patients must have evaluable or measurable disease according to Response
Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1. Patient with
bone-only metastases are eligible.
- 18. Willingness and ability to provide the most recent tumor biopsy since last
progression from either metastatic or primary tissues both at the time of the
inclusion and at disease progression or study termination in order to perform
exploratory studies. If not feasible, patient eligibility should be evaluated by a
Sponsor's qualified designee.
- 19. Patients must agree to provide blood samples at the time of study inclusion, every
three cycles of treatment, and upon disease progression or study termination in order
to perform exploratory studies.
- 20. Adequate hematologic and organ function within 28 days before the first study
treatment on Cycle 1 Day 1.
- 21. Female patients of childbearing potential must have a negative serum pregnancy
test within 3 days prior to study treatment and must agree to abstain from activities
that could result in pregnancy from screening through 6 months after the last dose of
study treatment, or patients of non-childbearing potential, where nonchildbearing
potential is defined as follows (by other than medical reasons):
- =45 years of age and has not had menses for >1 year;
- Patients who have been amenorrhoeic for <2 years without history of a
hysterectomy and oophorectomy must have levels of Luteinizing hormone (LH) and
Follicle stimulating hormone (FSH) in the post-menopausal range for women <50;
- Post-hysterectomy, post-bilateral oophorectomy, or posttubal ligation: documented
hysterectomy or oophorectomy must be confirmed with medical records of the actual
procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with
medical records of the actual procedure, otherwise the patient must be willing to
use 2 adequate barrier methods throughout the study, starting with the screening
visit through 6 months after the last dose of study treatment. Information must
be captured appropriately within the site's source documents.
- 22. Female patients must agree not to breastfeed during the study and for 1 month
after the last dose of study treatment.
- 23. Male patients whose partners are women of childbearing potential must use a condom
during niraparib therapy and for 3 months after receiving the last dose of niraparib
and must agree to abstain from activities that could result in pregnancy. In addition,
men must not donate sperm during niraparib therapy and for 3 months after receiving
the last dose of niraparib.
Exclusion Criteria:
- 1. HER2-positive disease based on local laboratory results (performed by IHC/in situ
hybridization test) or unknown HER2 status.
- 2. Patients that are candidates for a local treatment with a radical intention.
- 3. Patients that have previously received any PARP inhibitor (PARPi), including
niraparib, in metastatic setting. Note: Patients treated with PARPi on (neo)adjuvant
regimen with disease-free interval greater than 24 months following treatment
interruption are eligible.
- 4. Patients must not be simultaneously enrolled in any interventional clinical trial
and must not have received investigational therapy = 4 weeks, or within a time
interval less than at least 5 half-lives of the investigational agent, whichever is
shorter, prior initiating protocol therapy.
- 5. Patients who have had radiation therapy encompassing >20% of the bone marrow within
2 weeks prior to start of treatment, excepting for palliative radiation therapy to a
small field >1 week prior to Day 1 of study.
- 6. Patients with visceral crisis who require chemotherapy.
- 7. Patients must not have a known hypersensitivity to niraparib components or
excipients.
- 8. Patients must not have received a transfusion (platelets or red blood cells) = 4
weeks prior to initiating protocol therapy.
- 9. Patients must not have received colony-stimulating factors (e.g., Granulocyte
colony-stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor,
or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy.
- 10. Patients have had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia
due to prior chemotherapy in adjuvant setting or cyclin-dependent kinases (CDK)4/6
inhibitors that persisted > 4 weeks and was related to the most recent treatment.
- 11. Patients must not have any known history of Myelodysplastic syndrome (MDS) or
Acute myeloid leukemia (AML).
- 12. Patients must not have a serious, uncontrolled medical disorder, nonmalignant
systemic disease, or active, uncontrolled infection. Examples include, but are not
limited to, uncontrolled ventricular arrhythmia, recent (= 90 days) myocardial
infarction, uncontrolled major seizure disorder, unstable spinal cord compression,
superior vena cava syndrome, extensive interstitial bilateral lung disease on High
Resolution Computed Tomography (HRCT) scan, any psychiatric disorder that prohibits
obtaining informed consent, severe immunodeficiency disorders (i.e. human
immunodeficiency virus [HIV] infection) or active hepatitis (i.e. Hepatitis B or C).
- 13. Patients must not have had diagnosis, detection, or treatment of another type of
cancer = 2 years prior to initiating protocol therapy (except basal or squamous cell
carcinoma of the skin, cervical carcinoma in situ and ductal carcinoma in situ [DCIS]
definitively treated).
- 14. PPatients with symptomatic uncontrolled brain metastases or leptomeningeal
metastases. A scan to confirm the absence of brain metastases is not required.
Patients with spinal cord compression unless considered to have received definitive
treatment for this condition and have evidence of clinically stable disease (SD) for
35 days.
- 15. Previous allogenic bone marrow transplant or double umbilical cord blood
transplantation (dUCBT).
- 16. Patients who are unable to swallow orally administered medication.
- 17. Patients with gastrointestinal disorders likely to interfere with absorption of
the study medication.
- 18. Chronic daily treatment with corticosteroids with a dose of = 10 mg/day
methylprednisolone equivalent (excluding inhaled steroids), except for prophylaxis
use.
- 19. Female patients who are pregnant or breastfeeding, or adults of reproductive
potential who are not using effective birth control methods.
- 20 .Patients unwilling to or unable to comply with the protocol for the duration of
the study including undergoing treatment and scheduled visits and examinations.
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