Niraparib Plus Carboplatin in Patients With Homologous Recombination Deficient Advanced Solid Tumor Malignancies

Inclusion Criteria: * Patients PRE-identified as having either a germline deleterious mutation or tumor expression of a deleterious mutation) as determined by Next-generation DNA sequencing only, in at least one gene involved in DNA damage repair through homologous recombination including but not limited to: ARID1A, ATM, ATRX, MRE11A, NBN, PTEN, RAD50/51/51B, BARD1, BLM, BRCA1, BRCA2, BRIP1, FANCA/C/D2/E/F/G/L, PALB2, WRN, CHEK2, CHEK1, BAP1, FAM175A, SLX4, MLL2 or XRCC. * Patients with somatic mutations will be PRE-identified as having a homologous recombination mutation based on NGS done in a CLIA certified, CAP tested and bioinformatics-validated testing lab PRIOR to enrollment in this current protocol. The testing may have been done at any time prior to enrollment. HOWEVER, if any patient has had NGS testing more than 3 months prior to enrollment, or if there has been intervening therapy, then a repeat NGS test must be done and the deleterious somatic mutation must be re-identified for inclusion. * The determination of a deleterious mutation must be supported in the documentation included in the testing, and should include clinical, or pre-clinical literature to support the finding that a specific mutation results in impaired function of the gene, and thus impaired DNA repair through homologous recombination. Variants of unknown significance will not be eligible. * Patients with germline deleterious mutations may have been identified at any time point prior to inclusion in the protocol and do NOT need to have this genetic testing repeated regardless of time frame and intervening therapy. * Advanced, solid tumor malignancy that is amenable to biopsy. Patient must consent to 4 mandatory biopsies during study * Life expectancy of more than 3 months * Age ≥ 18 years * Measurable disease by RECIST v1.1 criteria (tumor ≥ 1 cm in longest diameter on axial image on computed tomography (CT) or magnetic resonance imaging (MRI) and/or lymph node(s) ≥ 1.5 cm in short axis on CT or MRI) on baseline imaging * ECOG performance status (PS) of 0 to 1 (Table 10, Appendix A) * Patients who have received and failed, or have been intolerant to, standard first line therapies known to confer clinical benefit. Patients who refuse standard therapy would also be eligible, as long as their refusal is documented. * Patients with a standard 12-lead electrocardiogram (ECG) with the following parameters at screening (defined as the mean of the triplicate ECGs): 1. QTc interval at screening \< 481 msec 2. Resting heart rate 50-90bpm * Adequate hepatic, bone marrow, and renal function at the time of enrollment: * Bone Marrow: Absolute neutrophil count (ANC) ≥ 1,500/mm3; Platelets ≥ 100,000/mm3; Hemoglobin ≥ 9.0 g/dL. Patients must be able to meet the criteria without transfusion or receipt of colony stimulating factors within 2 weeks before obtaining sample * Renal function: Serum creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 50 mL/min/1.73 m2 * Hepatic function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × the upper normal limit of institution's normal range. Total bilirubin ≤ 1.5 × the upper normal limit of institution's normal range. For subjects with liver metastases, AST and ALT \< 5 × the upper normal limit of institution's normal range, and total bilirubin \>1.5 - 3.0 x the upper normal limit of institution's normal range are acceptable as long as there is no persistent nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, or eosinophilia * Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) must be ≤ 2 X the upper limit of the institution's normal range and International Normalized Ratio (INR) \< 2. Subjects on anticoagulation (such as coumadin) will be permitted to enroll as long as the INR is in the acceptable therapeutic range as determined by the investigator * Patients may have received an unlimited number of prior therapies * Patients must have fully recovered from all effects of surgery. Patients must have had at least two weeks after minor surgery and four weeks after major surgery before starting therapy. Minor procedures requiring conscious sedation such as endoscopies or mediport placement may only require a 24-hour waiting period, but this must be discussed with an investigator * Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential * Patient is capable of swallowing pills whole * Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by the IRB, prior to the initiation of any screening or study-specific procedures Exclusion Criteria: * Prior disease progression while receiving platinum chemotherapy or platinum chemotherapy within the last 6 months * For patients who received platinum-based adjuvant chemotherapy, at least 6 months must have passed between the last dose of platinum-based therapy and the development of metastatic disease. For breast cancer patients, at least 12 months must have passed between the last dose of platinum-based therapy and the development of metastatic disease * Prior PARP inhibitor-based therapy * Known or suspected CNS metastases, unless at least one month has passed since last local CNS therapy and there is no evidence for recurrent or progressive CNS disease on follow up imaging. Participants may remain on steroids for CNS disease if they are taking a stable dose * Active severe infection, or known chronic infection with HIV or hepatitis B virus (testing not required prior to enrollment) * Patients with chronic Hepatitis C virus may be enrolled if there is no clinical/laboratory evidence of cirrhosis AND the patient's liver function tests fall within the parameters set in Section 3.2.8.3, Inclusion Criteria, Hepatic function * Cardiovascular disease problems including unstable angina, therapy for life-threatening ventricular arrhythmia, or myocardial infarction, stroke, or congestive heart failure within the last 6 months. Additionally, patients must not have QT prolongation greater than or equal to 481 milliseconds * Life-threatening visceral disease or other severe concurrent disease that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g. chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.) * Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) * Presence of a psychiatric illness or social situation that would limit compliance with study requirements * Women who are pregnant or breastfeeding * The subject must not have had diagnosis, detection, or treatment of another type of cancer ≤2 years prior to randomization (except basal or squamous cell carcinoma of the skin that has been definitively treated). Questions regarding the inclusion of individual subjects should be directed to the Principal Investigators, Dr. Isaacs and Dr. Pishvaian. * Clinically significant peripheral neuropathy at the time of enrollment (defined in the NCI CTCAE v4.0) as grade 2 or greater neurosensory or neuromotor toxicity) * Patients must not have had investigational therapy administered ≤4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study * Patients must not have had radiotherapy encompassing \>20% of the bone marrow * Patients must not have a known hypersensitivity to the components of niraparib or the excipients * Patients must not have had any known, persistent \> Grade 2 toxicity from prior cancer therapy * Patient must not have had any known, persistent (\>4 weeks), ≥Grade 3 hematological toxicity or fatigue from prior cancer therapy * Patients must not have current evidence of any condition, therapy, or laboratory abnormality (including active or uncontrolled myelosuppression \[ie, anemia, leukopenia, neutropenia, thrombocytopenia\]) that might confound the results of the study or interfere with the patient's participation for the full duration of the study treatment or that makes it not in the best interest of the patient to participate * Patients must not be considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant 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, or any psychiatric disorder that prohibits obtaining informed consent * Patient must not have any known history of myelodysplastic syndrome (MDS)