Last updated: 11/03/2018 11:49:00
VEG111485: A QTc study of pazopanib
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A Randomized, Blinded Placebo-Controlled Study to Evaluate the Effect of Repeat Oral Doses of Pazopanib (GW786034) on the Electrocardiogram (ECG) with Focus on Cardiac Repolarization (QTc duration) in Subjects with Solid Tumors
Trial description: This is a Phase I, randomized, double-blind, placebo-controlled, study to estimate the effects of daily oral dosing of 800 mg pazopanib on electrocardiographic parameters (QTc interval duration) as compared with placebo in subjects with solid tumors. Moxifloxacin, will serve as a positive control.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Change from baseline in QTcF interval at each time point on Study Day 9 (average of at least 3 Holter ECG replicates per time point) as compared with time-matched placebo.
Timeframe: 11 days
Secondary outcomes:
ECG parameters: RR interval, QT, QTcB, heart rate, PR, QRS intervals and morphology.
Timeframe: 11 days
Plasma pazopanib and metabolites (GSK1268992, GSK1268997 and GSK1071306) concentrations and PK parameters AUC(0-t), AUC(0-24), C24 Cmax and tmax as data permit.
Timeframe: 11 days
Change from baseline in QTcF interval at each time point on Study Day 1 (average of at least 3 Holter ECG replicates per time point) as compared with time-matched placebo.
Timeframe: 11 days
Plasma moxifloxacin concentrations and PK parameters AUC(0-t), AUC(0-∞), Cmax and tmax as data permit.
Timeframe: 11 days
Safety parameters: AEs, vital signs, ECGs and clinical laboratory assessments.
Timeframe: 11 days
Interventions:
Drug: Pazopanib
Other: Placebo for pazopanib
Drug: Moxifloxacin
Other: Placebo for moxifloxacin
Enrollment:
2
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Heath EI, Infante J, Lewis L, Luu T, Stephenson J, Tan A, Kasubhai S, LoRusso P, Dar MM, Ma B, Suttle B, Kleha J, Ball HA. A Phase I, Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Effect of Repeat Oral Doses of Pazopanib on Cardiac Conduction in Subjects with Solid Tumors . Cancer Chemother Pharmacol. 2013;71(3):565-73.
Heath EI, Infante J, Lewis L, et al. A Phase I, Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Effect of Repeat Oral Doses of Pazopanib on Cardiac Conduction in Subjects with Solid Tumors. Cancer Chemother Pharmacol. 2013;71(3):565-73.
Medical condition
Carcinoma, Renal Cell
Product
pazopanib
Collaborators
Not applicable
Study date(s)
March 2009 to February 2010
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Male or female, age 18 years or older, at the time of signing of the informed consent.
- Has histologically or cytologically confirmed advanced solid tumor malignancy.
- Any of the following ECG findings, QTcF interval >470 msec, PR interval >240 msec or ≤110msec, Bradycardia defined as sinus rate <50 beats per minute
- Cardiac conduction abnormalities denoted by any of the following: Evidence of second-degree (type II) or third-degree atrioventricular block, Evidence of ventricular pre-excitation, Electrocardiographic evidence of complete left bundle branch block (LBBB), Intraventricular conduction delay with QRS duration >120 msec, Atrial fibrillation, Presence of cardiac pacemaker.
Inclusion and exclusion criteria
Inclusion criteria:
- Male or female, age 18 years or older, at the time of signing of the informed consent.
- Has histologically or cytologically confirmed advanced solid tumor malignancy.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
- Able to swallow and retain oral medication.
- Adequate organ systems function.
- Serum potassium level >4 mEq/L, magnesium level >1.7 mg/dL and total serum calcium level within normal limits (if albumin is <4.5 g/dL, albumin-corrected total serum calcium level should be within normal limits [see Appendix 7]). NOTE: Supplementation is permitted in order to meet this criterion. Subject should be retested following supplementation.
- Subject is a woman of non-childbearing potential or willing to use acceptable contraception.
- Subject is a man with a female partner of childbearing potential agrees to use contraception.
- Subject, if sexually active, agrees to continue the recommended contraception method for the duration of treatment and for 28 days following discontinuation of treatment.
- Capable of giving written informed consent.
- The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
Exclusion criteria:
- Any of the following ECG findings, QTcF interval >470 msec, PR interval >240 msec or ≤110msec, Bradycardia defined as sinus rate <50 beats per minute
- Cardiac conduction abnormalities denoted by any of the following: Evidence of second-degree (type II) or third-degree atrioventricular block, Evidence of ventricular pre-excitation, Electrocardiographic evidence of complete left bundle branch block (LBBB), Intraventricular conduction delay with QRS duration >120 msec, Atrial fibrillation, Presence of cardiac pacemaker.
- History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, symptomatic peripheral vascular disease or other clinically significant cardiac disease.
- For subjects with a history of myocardial infarction (>6 months ago), congestive heart failure (>6 months ago) or prior anthracycline exposure, left ventricular ejection fraction (LVEF) must be assessed within 28 days prior to the first dose of study drug by one of the following methods: multiple gated acquisition (MUGA) scan or echocardiogram (ECHO). Subjects with a measurement of LVEF <50% are excluded from participation in the study.
- Personal or family history of long-QT syndrome.
- History or clinical evidence of CNS metastases or leptomeningeal carcinomatosis, except for individuals who have previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure medication for 2 months prior to beginning study treatment.
- Clinically significant gastrointestinal (GI) abnormalities that may affect the absorption of study drug including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel.
- Clinically significant GI abnormalities that may increase the risk for GI bleeding including, but not limited to: active peptic ulcer disease, known intra-luminal metastatic lesion(s) with suspected bleeding, inflammatory bowel disease, ulcerative colitis or other GI conditions with increased risk of perforation, history of abdominal fistula, GI perforation or intra-abdominal abscess within 28 days prior to beginning study treatment.
- Presence of uncontrolled infection.
- Unable or unwilling to discontinue use of prohibited medications listed in Section 9.2 for at least 14 days prior to the first dose of study drug (see Section 9.2).
- Poorly controlled hypertension [systolic blood pressure (SBP) >140 mmHg, or diastolic blood pressure (DBP) >90 mmHg].
- History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
- Evidence of active bleeding or bleeding diathesis.
- Hemoptysis within 6 weeks prior to the first dose of study drug.
- Known endobronchial lesion(s) or involvement of large pulmonary vessel(s) by tumor.
- History of sensitivity or allergic reaction to moxifloxacin or any member of the quinolone class of antimicrobial agents.
- Treatment with anti-cancer therapy (including chemotherapy, radiation therapy, immunotherapy, biologic therapy, investigational therapy, hormonal therapy, surgery or tumor embolization) within 14 days prior to the first dose of pazopanib.
- History or presence of hepatic or renal disease or any other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
- Prior major surgery or trauma within the past 28 days prior to the first dose of study drug and/or presence of any non-healing wound, fracture or ulcer.
- Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study.
Trial location(s)
Location
GSK Investigational Site
Duarte, California, United States, 91010
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37203
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Tacoma, Washington, United States, 98405
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Lebanon, New Hampshire, United States, 03756
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Santa Monica, California, United States, 90404
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Detroit, Michigan, United States, 48201
Status
Terminated/Withdrawn
Location
GSK Investigational Site
New Brunswick, New Jersey, United States, 08901
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Greenville, South Carolina, United States, 29605
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
Not applicable
Actual study completion date
2010-15-02
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
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Additional information
Results for study 111485 can be found on the GSK Clinical Study Register.
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