This phase I trial studies the side effects and the best dose of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor BMN-673 when given together with temozolomide or irinotecan hydrochloride in treating patients with locally advanced or metastatic solid tumors. PARP inhibitor BMN-673 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and may help temozolomide and irinotecan hydrochloride work better by making tumor cells more sensitive to the drug. Drugs used in chemotherapy, such as temozolomide and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving PARP inhibitor BMN-673 with temozolomide or irinotecan hydrochloride may be an effective treatment for patients with advanced solid tumors.

PRIMARY OBJECTIVES:

I. To assess the safety and tolerability and to estimate the maximum tolerated dose (MTD) of the following combinations in participants with advanced solid tumors: Arm A: BMN 673 (PARP inhibitor BMN-673) and temozolomide; Arm B: BMN 673 and irinotecan (irinotecan hydrochloride).

SECONDARY OBJECTIVES:

I. To evaluate the pharmacokinetics of BMN 673, temozolomide, and irinotecan when BMN 673 is given in combination with temozolomide (Arm A) or irinotecan (Arm B). To assess the effects of temozolomide and irinotecan in Arms A and B respectively on the pharmacokinetics of BMN 673.

II. To evaluate biomarkers that correlate with effect of BMN 673 in combination with temozolomide or irinotecan.

III. To document any anti-tumor activity.

OUTLINE: This is a dose-escalation study of PARP inhibitor BMN-673. Patients are assigned to 1 of 2 treatment arms.

ARM A: Patients receive PARP inhibitor BMN-673 orally (PO) once daily (QD) on days 1-28 and temozolomide PO daily on days1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive PARP inhibitor BNM-673 as in Arm A and irinotecan hydrochloride intravenously (IV) on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 12 months.

Inclusion Criteria:

• Histologically or cytologically documented, unresectable, locally advanced or metastatic solid tumor for which no standard therapy is recognized or for which standard therapy has failed
• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST, v1.1)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN); if liver function abnormalities are due to hepatic metastasis, then AST and ALT may be =< 5 x ULN
• Total serum bilirubin =< 1.5 x ULN
• Calculated creatinine clearance of >= 40 ml/min; as per Cockcroft-Gault formula
• Hemoglobin >= 9.0 g/dL
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelet count >= 100,000/mm^3
• Able to take oral medications
• Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures
• Sexually active patients must be willing to use an acceptable method of contraception such as double barrier contraception during treatment and for 30 days after the last dose of BMN 673
• Females of childbearing potential must have a negative serum pregnancy test at screening

Exclusion Criteria:

• Has not recovered (recovery is defined as National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE version (v)4.03] grade =< 1) from the acute toxicities of previous therapy, except treatment-related alopecia or laboratory abnormalities otherwise meeting the inclusion requirements stated in the inclusion criterion

• Prior treatment with a PARP inhibitor

• Prior allergic reaction or severe intolerance to either irinotecan or temozolomide

• History of central nervous system (CNS) metastasis that are untreated or not stable

• Any antitumor systemic cytotoxic therapies within 28 days prior to enrollment (6 weeks for nitrosoureas or mitomycin-C); prior high-dose chemotherapy with bone marrow or stem cell transplant is excluded

• Is known to have human immunodeficiency virus (HIV) or has active hepatitis C virus (HCV), or active hepatitis B virus (HBV)

• Has had major surgery within 28 days prior to enrollment

• Active gastrointestinal tract disease with malabsorption syndrome

• Requirement for IV alimentation

• Uncontrolled inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)

• Symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or unstable cardiac arrhythmia requiring medication (atrial fibrillation is permitted)

• Use of any investigational product or investigational medical device within 28 days prior to enrollment

• Concurrent disease or condition that would interfere with study participation or safety, such as:

  • Active, clinically significant infection requiring the use of parenteral anti-microbial agents, or grade > 2 by NCI CTCAE (v 4.03) within 14 days prior to enrollment
  • Clinically significant bleeding diathesis or coagulopathy, including known platelet function disorders
  • Non-healing wound, ulcer, or bone fracture
  • Bone marrow disorder including myelodysplasia