A Study to Evaluate the Effects of Veliparib on Heart Rhythms in Patients With Solid Tumors

Study Overview
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Brief Summary
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This is a randomized Phase 1 study to evaluate the effects of Veliparib on cardiac repolarization in patients with solid tumors who's cancer has recurred or is no longer responding to current treatment.

Official Title
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A Randomized, Placebo-Controlled Crossover Study to Evaluate the Effect of Veliparib (ABT-888) on Cardiac Repolarization in Subjects With Relapsed or Refractory Solid Tumors

Conditions
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Breast Cancer, Ovarian Cancer, Colon Cancer, Lung Cancer, Gastric Cancer, Solid Tumors

Intervention / Treatment
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* Drug: Veliparib (ABT-888)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed solid malignancy that is metastatic or unresectable for which standard curative measures or other therapy that may provide clinical benefit do not exist or are no longer effective. Subjects with brain metastases must have clinically controlled neurologic symptoms. Subject is able to swallow and retain oral medications and does not have uncontrolled emesis. Subject has adequate bone marrow, renal and hepatic function per local laboratory reference ranges. Exclusion Criteria: Uncorrected serum potassium, serum magnesium, serum calcium or free thyroxin (FT4) and thyroid stimulating hormone (TSH) outside of normal reference ranges, or grade 2 hyponatremia or hypernatremia. Subject has severe ECG morphologic abnormalities that make QTc evaluation difficult. Subject has a history of cardiac conduction abnormalities. Subject has a significant history of cardiovascular disease. Subject has received any anti-cancer therapies 21 days prior to the first dose of study drug, or has recovered to no better than a grade 2 or higher clinically significant adverse effect(s)/toxicity(s) of the previous therapy. Use of drugs with a known risk for QT prolongation and Torsades de Pointes within 7 days prior to the first study dose. Use of tobacco or nicotine-containing products within 12 hours prior to the first study dose.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence Group A<br>200 mg Veliparib | Drug: Veliparib (ABT-888)<br> <br> |
| Experimental: Sequence Group B<br>400 mg Veliparib | Drug: Veliparib (ABT-888)<br> <br> |
| Placebo Comparator: Sequence Group C<br>Placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the effect of Veliparib on corrected QT interval calculated by Fridericia's formula (QTcF) |  | Electrocardiograms (ECGs) will be done at Screening, 6 time points on Day 1 of Periods 1, 2 and 3 in triplicate, 1 time point on Day 2 of Periods 1, 2, and 3 and 1 time point on Day 3 of Period 3. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic sampling maximum observed plasma concentration (Cmax) |  | Pharmacokinetic samples will be drawn at Screening, 6 time points on Day 1 of Periods 1, 2 and 3 and 1 time point on Day 2 of Periods 1, 2, and 3. | 
| Pharmacokinetic sampling - time to maximum observed plasma concentration (Tmax) |  | Pharmacokinetic samples will be drawn at Screening, 6 time points on Day 1 of Periods 1, 2 and 3 and 1 time point on Day 2 of Periods 1, 2, and 3. | 
| Pharmacokinetic sampling - the area under the plasma concentration-time curve (AUC) from time 0-24 hours (AUC 0-24) |  | Pharmacokinetic samples will be drawn at Screening, 6 time points on Day 1 of Periods 1, 2 and 3 and 1 time point on Day 2 of Periods 1, 2, and 3. | 
| The number of subjects with adverse events |  | Up to 30 days after last dose of study drug. | 
| Vital Signs | Blood pressure, heart rate and temperature. | Up to 30 days after last dose of study drug. | 
| Clinical Laboratory Tests | Hematology, chemistry, urinalysis | Up to 30 days after last dose of study drug. | 
| Tumor Assessment | A computerized tomography scan will be done at screening to document tumor size. | Screening | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumors, Ovarian Cancer, Colon Cancer, Lung Cancer, Breast Cancer, Gastric Cancer