Clinical trial NCT02009631: A Study to Evaluate the Effects of Veliparib on Heart Rhythms in Patients With Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Ovarian Cancer
Colon Cancer
Lung Cancer
Gastric Cancer
Solid Tumors
Keywords: Solid Tumors
Ovarian Cancer
Colon Cancer
Lung Cancer
Breast Cancer
Gastric Cancer
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2013-12-12
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: To evaluate the effect of Veliparib on corrected QT interval calculated by Fridericia's formula (QTcF)
timeFrame: 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 outcomes:
measure: Pharmacokinetic sampling maximum observed plasma concentration (Cmax)
timeFrame: 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.
measure: Pharmacokinetic sampling - time to maximum observed plasma concentration (Tmax)
timeFrame: 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.
measure: Pharmacokinetic sampling - the area under the plasma concentration-time curve (AUC) from time 0-24 hours (AUC 0-24)
timeFrame: 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.
measure: The number of subjects with adverse events
timeFrame: Up to 30 days after last dose of study drug.
measure: Vital Signs
timeFrame: Up to 30 days after last dose of study drug.
measure: Clinical Laboratory Tests
timeFrame: Up to 30 days after last dose of study drug.
measure: Tumor Assessment
timeFrame: Screening
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Site Reference ID/Investigator# 116015
state: Arizona
city: San Antonio
country: United States
facility: Site Reference ID/Investigator# 116016
state: Texas
city: Groningn
country: Netherlands
facility: Site Reference ID/Investigator# 117320
city: Maastricht
country: Netherlands
facility: Site Reference ID/Investigator# 117336
city: Madrid
country: Spain
facility: Site Reference ID/Investigator# 117517
Study officials:
affiliation: AbbVie
name: Stacie Shepherd, PhD
role: STUDY_DIRECTOR
References:
citation: Munasinghe W, Stodtmann S, Tolcher A, Calvo E, Gordon M, Jalving M, de Vos-Geelen J, Medina D, Bergau D, Nuthalapati S, Hoffman D, Shepherd S, Xiong H. Effect of veliparib (ABT-888) on cardiac repolarization in patients with advanced solid tumors: a randomized, placebo-controlled crossover study. Cancer Chemother Pharmacol. 2016 Nov;78(5):1003-1011. doi: 10.1007/s00280-016-3156-x. Epub 2016 Oct 5.