Study of Poly (ADP-Ribose) Polymerase (PARP) Inhibitor E7016 in Combination With Temozolomide in Subjects With Advanced Solid Tumors

Inclusion Criteria

• •Subjects who meet all of the following criteria may be included in the study.
• •1. Histopathologically confirmed melanoma or other solid tumors (excluding malignant brain tumors) for which no standard therapy is available (Dose-Escalation Component only). During the Expansion Component, enrollment will be restricted to subjects with histopathologically proven gliomas and will include subjects eligible for TMZ therapy as well as those who have failed TMZ therapy; and those who are either not appropriate candidates for radiation therapy or who refuse radiation therapy. Subjects who are taking either strong cytochrome P450 (CYP) inhibitors or inducers may be enrolled.
• •2. Life expectancy greater than or equal to 3 months after starting E7016.
• •3. Performance status (PS) 1 to 2 on the Eastern Cooperative Oncology Group (ECOG) scale.
• •4. Adequate renal function indicated by serum creatinine less than 1.5 mg/dL or calculated creatinine clearance greater than 50 mL/minute.
• •5. Adequate bone marrow reserve:
• •1. ANC greater than or equal to 1500/mm3,
• •2. Platelets greater than or equal to 100,000/mm3 (without transfusion),
• •3. Hemoglobin greater than or equal to 10 g/dL (less than 10.0 g/dL is acceptable if corrected by growth factor or transfusion).
• •6. Adequate liver function:
• •1. Bilirubin less than or equal to 1.5x the upper limit of normal (ULN) (less than or equal to 3 x ULN if subject has liver metastases),
• •2. Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3 times ULN (less than or equal to 5 x ULN if subject has liver metastases).
• •7. Males and females age greater than or equal to 18 years at the time of informed consent.
• •1. Female subjects of childbearing potential must have a negative serum beta human chorionic gonadotropin (BhCG) test at Visit 1 (Screening) and a negative urine pregnancy test prior to the first dose of E7016 capsules in the Single-Dose PK Period and again prior to the first dose of E7016 in Cycle 1.
• •2. Male subjects who are partners of women of childbearing potential must use or their partners must use a highly effective method of contraception (eg, condom + spermicide, condom + diaphragm with spermicide, IUD) beginning at least 1 menstrual cycle prior to starting study drug(s), throughout the entire study period, and for 30 days after the last dose of study drug.