Veliparib and Topotecan Hydrochloride in Treating Patients With Solid Tumors, Relapsed or Refractory Ovarian Cancer, or Primary Peritoneal Cancer
|ClinicalTrials.gov Identifier: NCT01012817|
Recruitment Status : Suspended (Other - assess toxicity and perform interim analysis.)
First Posted : November 13, 2009
Last Update Posted : August 3, 2018
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Malignant Solid Neoplasm Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Unresectable Solid Neoplasm||Other: Laboratory Biomarker Analysis Other: Pharmacogenomic Study Other: Pharmacological Study Drug: Topotecan Hydrochloride Drug: Veliparib||Phase 1 Phase 2|
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)
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||102 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||October 29, 2009|
|Estimated Primary Completion Date :||August 31, 2020|
Experimental: Treatment (veliparib and topotecan hydrochloride)
Patients receive veliparib PO on days 1-3, 8-10, and 15-17 (veliparib is omitted on days 1-3 of course 2) and topotecan hydrochloride IV over 30 minutes on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Pharmacogenomic Study
Other Name: PHARMACOGENOMIC
Other: Pharmacological Study
Drug: Topotecan Hydrochloride
- Maximum tolerated dose of topotecan hydrochloride and veliparib, determined according to incidence of dose-limiting toxicity, graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase I) [ Time Frame: 4 weeks ]The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized. The grade 3+ adverse events will also be described and summarized in a similar fashion. Toxicity incidence by BRCA mutation will also be evaluated for the patients enrolled in the expanded Phase I maximum tolerated dose cohort. Frequency distribution, graphical techniques, and other descriptive measures will form the basis of these analyses.
- Proportion of tumor responses, defined as complete response or partial response as assessed using Response Evaluation Criteria In Solid Tumors [ Time Frame: Up to 48 weeks (12 courses) ]The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner (1987).
- Overall survival [ Time Frame: The time from registration to death due to any cause, assessed up to 5 years ]The distribution of survival time will be estimated using the method of Kaplan-Meier.
- Progression free survival [ Time Frame: The time from registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 5 years ]The distribution of progression free survival will be estimated using the method of Kaplan-Meier.
- Duration of response [ Time Frame: Up to 5 years ]Duration of response is defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a complete response or partial response to the earliest date progression is documented.
- Time to treatment failure [ Time Frame: The time from the date of registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal, assessed up to 5 years ]Time to treatment failure is defined to be the time from the date of registration to the date at which the patient is removed from treatment due to progression, adverse events, or refusal.
- Adverse events, graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 5 years ]The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01012817
|United States, Arizona|
|Mayo Clinic Hospital|
|Phoenix, Arizona, United States, 85054|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, California|
|University of California Davis Comprehensive Cancer Center|
|Sacramento, California, United States, 95817|
|United States, Colorado|
|University of Colorado Hospital|
|Aurora, Colorado, United States, 80045|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224-9980|
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637|
|UC Comprehensive Cancer Center at Silver Cross|
|New Lenox, Illinois, United States, 60451|
|University of Chicago Medicine-Orland Park|
|Orland Park, Illinois, United States, 60462|
|United States, Kansas|
|University of Kansas Clinical Research Center|
|Fairway, Kansas, United States, 66205|
|United States, Kentucky|
|University of Kentucky/Markey Cancer Center|
|Lexington, Kentucky, United States, 40536|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, Pennsylvania|
|University of Pittsburgh Cancer Institute (UPCI)|
|Pittsburgh, Pennsylvania, United States, 15232|
|United States, Texas|
|Parkland Memorial Hospital|
|Dallas, Texas, United States, 75235|
|UT Southwestern/Simmons Cancer Center-Dallas|
|Dallas, Texas, United States, 75390|
|United States, Utah|
|Huntsman Cancer Institute/University of Utah|
|Salt Lake City, Utah, United States, 84112|
|Principal Investigator:||Andrea Wahner Hendrickson||Mayo Clinic Cancer Center LAO|