Trials / Active Not Recruiting

Active Not RecruitingNCT01012817

Veliparib and Topotecan Hydrochloride in Treating Patients With Solid Tumors, Relapsed or Refractory Ovarian Cancer, or Primary Peritoneal Cancer

A Phase 1/2 Trial of ABT-888, an Inhibitor of Poly(ADP-ribose) Polymerase (PARP), and Topotecan (TPT) in Patients With Solid Tumors (Phase 1) and Relapsed Ovarian Cancer or Primary Peritoneal Cancer (Phase 2) After Prior Platinum Containing First-Line Chemotherapy

Status: Active Not Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 88 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the side effects and best dose of veliparib and topotecan hydrochloride and to see how well they work in treating patients with solid tumors, ovarian cancer that has come back or does not respond to treatment, or primary peritoneal cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as topotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib with chemotherapy may kill more tumor cells.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose of the combination of veliparib (ABT-888) and weekly topotecan (topotecan hydrochloride) in adult patients with advanced solid tumors. (Phase I) II. To identify any anti-tumor activity of this treatment combination, as assessed by objective response in patients with advanced solid tumors. (Phase I) III. To assess the confirmed response rate for patients with epithelial ovarian cancer, fallopian tube cancer or primary peritoneal carcinoma treated with the combination of ABT-888 and weekly topotecan. IV. To assess the progression free response (PFS) for patients with epithelial ovarian cancer, fallopian tube cancer or primary peritoneal carcinoma treated with the combination of ABT-888 and weekly topotecan. (Phase II) SECONDARY OBJECTIVES: I. To identify any pharmacokinetic interactions between ABT-888 and topotecan. (Phase I) II. To determine whether topotecan stimulates adenosine diphosphate (ADP)-ribose polymer formation in circulating peripheral blood mononuclear cells. (Phase I) III. To determine whether ABT-888 inhibits basal or topotecan-stimulated ADP-ribose polymer formation. (Phase I) IV. To assess differences in the toxicity and/or efficacy of this regimen based on BRCA 1/2 mutational status. (Phase II) V. To determine whether pretreatment tumor cell levels of topoisomerase I, poly ADP-ribose polymerase (PARP), BRCA1, BRCA2, XRCC1, tyrosyl-deoxyribonucleic acid (DNA) phosphodiesterase 1 (TDP1), P-glycoprotein or breast cancer resistance protein (BCRP) predict response to this regimen. (Phase II) VI. To identify, in an exploratory manner, any transcriptional profiles that may predict response to this regimen. (Phase II) OUTLINE: This is a phase I, dose-escalation study of veliparib and topotecan hydrochloride followed by a phase II study. (PHASE I DOSE-ESCALATION PART IS COMPLETED) Patients receive veliparib orally (PO) on days 1-3, 8-10, and 15-17 (veliparib is omitted on days 1-3 of course 2) and topotecan hydrochloride intravenously (IV) over 30 minutes on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 3 months (Phase I) or every 3 or 6 months for 5 years (Phase II).

Conditions

Interventions

Type	Name	Description
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacogenomic Study	Correlative studies
OTHER	Pharmacological Study	Correlative studies
DRUG	Topotecan Hydrochloride	Given IV
DRUG	Veliparib	Given PO

Timeline

Start date: 2009-11-03
Primary completion: 2019-01-13
Completion: 2026-08-27
First posted: 2009-11-13
Last updated: 2025-09-15
Results posted: 2023-07-19

Locations

15 sites across 1 country: United States

Source: ClinicalTrials.gov record NCT01012817. Inclusion in this directory is not an endorsement.