Protocol Title:

A Phase 1 Study Evaluating the Safety, Tolerability
and Pharmacokinetics of ABT-888 in Combination
with Whole Brain Radiation Therapy in Subjects with Brain Metastases

Protocol Status:

Open

Protocol Number:

J-07126

Type of Cancer:

Metastatic Brain Cancer

Principal Investigator:

Lawrence Kleinberg, M.D.

Research Nurse:

Shirl DiPasquale, R.N.

Phase Number:

I

General Eligibility:

Males or females greater than or equal to 18 years of age with  confirmed non-central nervous system primary solid malignancy.
Confirmed  metastatic disease in the brain. Subjects with non-measurable lesions, including leptomeningeal carcinomatosis are eligible. WBRT is clinically indicated, with the exception of prophylactic treatment. Karnofsky Performance Status (KPS) greater than or equal to a score of 70. Adequate hematologic, hepatic, and renal function. Prior or concurrent administration of some therapies or treatments are permitted but are limited.

Purpose:

The primary objectives of this study are to evaluate the safety, tolerability, and to determine the maximum-tolerated dose (MTD) and/or the recommended phase two dose (RPTD).
The secondary objectives are to characterize the pharmacokinetics of ABT-888 administered concurrently with conventional WBRT in the treatment of subjects with solid primary tumors metastatic to the brain; and to evaluate the effect of food on the pharmacokinetic profile.

Treatment:

All eligible subjects will receive ABT-888 and WBRT on an outpatient basis starting on WBRT Day 1. Subjects enrolled in the study will receive WBRT delivered in 2.5 Gy fractions QD for a total of 15 fractions administered over 15 consecutive days, excluding weekends and holidays. The total planned dose is 37.5 Gy. The initial dose of ABT-888 will be 10 mg BID. ABT-888 will be administered continuously throughout the entire course of WBRT; one additional day of ABT-888 dosing will follow the final session of WBRT. ABT-888 will be escalated in subsequent cohorts until determination of the MTD and/or RPTD. ABT-888 M10-128 Protocol 16 Subjects will self-administer the morning and evening doses of ABT-888 orally, with or without food, approximately 12 hours apart in the same calendar day.