Study Evaluating the Antitumor Activity and Safety of Niraparib as Neoadjuvant Treatment in Participants With Breast Cancer
Condition: Neoplasms, Breast
MeSH terms: Breast Neoplasms
Intervention: Niraparib
Intervention description: Niraparib is a potent, orally active, highly selective poly adenosine diphosphate ([ADP]-ribose) polymerase 1 (PARP1) and PARP2 inhibitor. It will be supplied as 100 mg capsules and will be administered at starting dose of 200 mg PO daily throughout 28 days for 2 cycles (each cycle is 28 days), with the potential for an additional 4 cycles (maximum total of 6 cycles) at the assigned dose and schedule.
Intervention MeSH terms: Niraparib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Niraparib; Human epidermal growth factor receptor; Breast cancer; Breast ultrasound; Magnetic resonance imaging

Summary:

      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.
    

Eligibility criteria:

        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).