ABT-888, Carboplatin, and Paclitaxel for Cancer With Liver or Kidney Problems

Neoplasms Clinical Trial

Official title: An Early Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Patients With Hepatic or Renal Dysfunction and Solid Tumors

Status Withdrawn

Clinical Trial Summary

Background:

• Paclitaxel and carboplatin are two standard drugs that stop cancer cells from reproducing. ABT-888 is an experimental cancer drug that may prevent cancer cells from "fixing" the damage done by chemotherapy drugs. This may make the chemotherapy work better. More tests are needed to determine the safety and effectiveness of ABT-888 plus chemotherapy. Researchers also want to find the best dose of ABT-888 for people who have kidney or liver problems in addition to cancer.

Objectives:

• To test the safety and effectiveness of ABT-888 plus carboplatin and paclitaxel in people who have both cancer and kidney or liver problems.

Eligibility:

• Individuals at least 18 years of age who have solid tumors that have not responded to standard treatment, and who also have kidney or liver problems.

• A small group of people with solid tumors and normal kidney and liver function may also receive treatment for study comparison purposes.

Design:

• Participants will be screened with a medical history and physical exam. They will have blood and urine tests, tumor samples, tests of liver and kidney function, and imaging studies. Participants will also provide a hair sample at the start of the study.

• Participants will take one dose of ABT-888 1 week before starting chemotherapy. The two chemotherapy drugs will be given on day 3 of a 21-day cycle. Participants will take ABT-888 daily for the first 7 days of each cycle.

• They will keep a diary to record medication doses and any side effects. They will also have frequent blood tests and imaging studies. Participants will provide more hair samples on day 3 of cycle 1 before and after having paclitaxel.

• Participants will continue treatment for up to 18 weeks as long as the cancer stops growing or shrinks and there are no serious side effects. Participants may have the option to continue treatment after the study is done.

Clinical Trial Description

Background:

The poly (ADP-ribose) polymerase (PARP) family of enzymes is critical for maintaining genomic stability by regulating a variety of DNA repair mechanisms. The carboplatin/paclitaxel combination has demonstrated a wide spectrum of clinical antitumor activity, making it an ideal platform for evaluation with novel agents, such as the PARP inhibitor ABT-888.

Objectives:

To determine the pharmacokinetics and pharmacodynamics of ABT-888 in patients with varying degrees of renal or hepatic dysfunction.

To determine the maximum tolerated dose (MTD) of ABT-888 in combination with carboplatin and paclitaxel for patients with varying degrees of liver or kidney dysfunction.

To provide dosing recommendations for ABT-888 in combination with carboplatin and paclitaxel based on degree of hepatic and renal impairment.

To define the dose-limiting toxicity and other toxicities associated with the use of this combination in patients with varying degrees of renal or hepatic dysfunction.

To evaluate the pharmacokinetic parameters of ABT-888, carboplatin and paclitaxel when administered as a combination in patients with varying degrees of renal or hepatic dysfunction.

To evaluate the pharmacodynamic measurement of PAR and platinum adducts in peripheral blood mononuclear cells (PBMC) and tumor cells associated with the use of this combination

in patients with varying degrees of renal or hepatic dysfunction.

Eligibility:

Patients must have histologically confirmed malignancy that is metastatic or unresectable, for which standard curative or palliative measures do not exist or are no longer effective, and for which there is expectation of response to the combination of carboplatin/paclitaxel (e.g., lung, ovarian, breast, and melanoma).

Patients must have adequate bone marrow function.

Patients with normal organ function, patients with all degrees of renal dysfunction, and patients with mild to severe hepatic dysfunction are allowed.

Study Design:

ABT-888 (80 mg) will be given orally on day -6 ( 1 day) of cycle 1 in all cohorts. ABT-888 in varying doses will then be given on days 1-7 of each cycle, with the dose depending on each patient's degree of renal or hepatic dysfunction.

Fixed doses of chemotherapy will be given intravenously on day 3 of each cycle. For patients with renal dysfunction, carboplatin will be given at AUC of 6 and paclitaxel at 175 mg/m2. For patients with hepatic dysfunction, carboplatin will be given at AUC of 6 and paclitaxel at doses adjusted to each patient's degree of hepatic dysfunction.

The dose of ABT-888 will be escalated to determine the MTD of the combination. ;

Related Conditions & MeSH terms

• Neoplasms

• NCT number: NCT01419548
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Withdrawn
• Phase: Phase 1
• Start date: July 29, 2011
• Completion date: November 18, 2011