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.
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).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
88
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, United States
Mayo Clinic in Florida
Jacksonville, Florida, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
UC Comprehensive Cancer Center at Silver Cross
New Lenox, Illinois, United States
University of Chicago Medicine-Orland Park
Orland Park, Illinois, United States
University of Kansas Clinical Research Center
Fairway, Kansas, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
...and 5 more locations
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)
The number of patients with a dose limiting toxicity will be reported. Dose-limiting toxicity (DLT) will be defined as a cycle 1 adverse event attributed (definitely, probably, or possibly) to the study treatment and meeting the following criteria: Grade 4 anemia, grade 4 neutrophil count decrease, grade 4 platelet count decrease, Serum creatinine \>= 2 times baseline or ≥ 2 times the upper limit of normal if baseline is \< the upper limit of normal, or other \>= Grade 3 as per NCI Common Terminology Criteria for Adverse Events CTCAE version 4.0. \>= Grade 3 nausea, vomiting, or diarrhea with maximal supportive treatment(s) will be considered dose-limiting. Grade 3 fatigue or anorexia will not be considered dos
Time frame: 4 weeks
Percent of Patients With Tumor Response, Defined as Complete Response or Partial Response as Assessed Using Response Evaluation Criteria In Solid Tumors
The proportion of successes will be estimated by the number of successes(CR or PR) 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). Complete Response (CR) is defined as disappearance of all target lesions and, if non target lesions exist, the disappearance of all non-target lesions and normalization of tumor maker level. At least 30% decrease in the sum of the longest diameter (LD) of target lesion taking as reference the baseline sum.
Time frame: Up to 48 weeks (12 courses)
Overall Survival
The distribution of survival time for phase 2 patients will be estimated using the method of Kaplan-Meier.
Time frame: The time from registration to death due to any cause, assessed up to 5 years
Progression Free Survival
The distribution of progression free survival will be estimated using the method of Kaplan-Meier.
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
Duration of Response
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 frame: Up to 5 years
Time to Treatment Failure
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.
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
Adverse Events, Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
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.
Time frame: Up to 5 years
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