Safety Study of ABT-888 Plus Topotecan Hydrochloride to Treat Patients With Solid Tumors and Lymphomas
Status:
Completed
Trial end date:
2011-09-28
Target enrollment:
Participant gender:
Summary
Background:
- PARP is an enzyme that is involved in the repair of damage to DNA. Levels of the enzyme
are higher in tumor cells than in normal cells, and may play a part in resistance to
cancer chemotherapy and radiation therapy. ABT-888 is an experimental drug that inhibits
PARP and may help to increase the effectiveness of cancer treatments designed to damage
DNA in cancer cells.
- Topotecan is a drug approved by the Food and Drug Administration for treating certain
cancers.
- This dose escalation study will test the two drugs at successively higher doses in small
groups of patients until the highest safe dose is determined.
Objectives:
- To test the safety of the combination of ABT-888 and Topotecan (TPT) and determine the
highest dose of each drug that can be safely given to humans. This is the maximum
tolerated dose (MTD).
- To learn how the combination of ABT-888 and TPT works in humans and how the body handles
the drugs.
- To determine the side effects of the combination of ABT-888 and TPT at the tested doses.
Eligibility:
-Patients with solid tumors, lymphomas and chronic lymphocytic leukemia whose disease has
progressed following standard therapy or for whom standard treatments are not available.
Design:
- ABT-888 and TPT are given in 21-day treatment cycles. At the start of the study, TPT is
infused through a vein over 30 minutes about a week before cycle 1 starts. Starting on
day 1 of cycle 1, ABT-888 is given by mouth twice a day for 7 days. TPT is given through
a vein daily for 4 days starting on day 2. After the last dose of ABT-888 day 7, no more
treatment is given for the rest of the 21-day cycle.
- For the remaining cycles, ABT-888 is given twice a day by mouth on days 1 to 7 of each
cycle, and TPT is given through a vein daily on days 1 to 5 of each cycle.
- The first three to six patients enrolled in the study take the smallest study dose of
the drugs. If they do not develop significant adverse side effects, successive small
groups of patients take the drug at increasingly higher doses until the MTD is reached.
Additional patients enrolled receive the MTD.
- Patients have periodic clinic visits for their TPT infusions and for tests and
examinations. Evaluations include measurement of vital signs, physical examinations,
blood and urine tests, electrocardiograms and CT or other imaging tests, such as
ultrasound or MRI. Tumor biopsies may be requested to study the effects of the drugs on
the...