A Study to Evaluate the Safety, Pharmacokinetics and Oral Bio Availability of Veliparib in Subjects With Solid Tumors

Inclusion Criteria

• •1. Part 1 and 2: Histologically or cytologically confirmed malignancy that is metastatic or unresectable and for which standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective. Subjects must also 1) have a documented BRCA1 or BRCA2 mutation that is considered to be deleterious by the investigator, OR 2) have high grade serous ovarian, fallopian tube, or peritoneal cancer. Subjects with molecular features indicative of DNA repair defects (such as mutation in the Fanconi anemia pathway genes or methylation of the BRCA1 promoter) may be considered eligible for following discussion with the medical monitor. Part 3: Histologically or cytologically confirmed breast, ovarian, fallopian tube or primary peritoneal cancer that is metastatic or unresectable and for which standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective. Platinum-resistant ovarian cancer is not permitted. Subjects must also 1) have a documented BRCA1 or BRCA2 mutation that is considered to be deleterious by the investigator and 2) have received 3 or fewer regimens of cytotoxic chemotherapy in the metastatic setting and 3) have evaluable disease as defined by RECIST 1.1 or GCIC-CA-125 criteria.
• •2. Subject must be at least 18 years of age.
• •3. Completion of last anti-cancer therapy must be at least 28 days prior to study drug administration.
• •4. Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2.
• •5. Subject must have adequate hematologic, renal and hepatic function as follows:
• •* Bone Marrow: Absolute neutrophil count ANC ≥ 1,500/mm3 (1.5 × 109/L); Platelets ≥ 100,000/mm3 (100 × 109/L); Hemoglobin ≥ 9.5 g/dL (1.4 mmol/L). Subjects with hemoglobin ≥ 9.5 g/dL (1.4 mmol/L) following transfusion are eligible;
• •* Renal function: A calculated creatinine clearance value of ≥ 50 mL/min as determined by the Cockcroft Gault formula or a creatinine clearance value of ≥ 50 mL/min based on a 24-hour urine collection;
• •* Hepatic function: AST and ALT ≤ 2.5 × 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;
• •* Bilirubin: → 1.5 × the upper normal limit of institution's normal range.
• •6. Women of childbearing potential and men must agree to use adequate contraception prior to the study entry, for the duration of study participation and up to 3 months following completion of therapy. Women of childbearing potential must have a negative pregnancy test within 7 days prior to initiation of treatment and/or post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
• •* total abstinence from sexual intercourse as the preferred life style of the subject; periodic abstinence is not acceptable;
• •* vasectomized partner(s);
• •* hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration;
• •* intrauterine device (IUD);
• •* Male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and for 90 days following completion if therapy.
• •7. Subject must be capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent, approved by an Institutional Review Board (IRB) prior to the initiation of any screening or study specific procedures.
• •8. Must voluntarily sign and date each informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.