Carcinoma, Renal CellPhase 1NCT00861029
VEG111485: A QTc Study of Pazopanib
A Phase 1 study testing Pazopanib and Moxifloxacin in people with Carcinoma, Renal Cell, run by GlaxoSmithKline at 8 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Renal Cell
- What is being tested?
- Pazopanib and Moxifloxacin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 8 sitesUnited States
- Study dates
- 19 Mar 2009to 15 Feb 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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 locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
GSK Investigational Site
Detroit, Michigan, 48201
GSK Investigational Site
Duarte, California, 91010
GSK Investigational Site
Greenville, South Carolina, 29605
GSK Investigational Site
Lebanon, New Hampshire, 03756
GSK Investigational Site
Nashville, Tennessee, 37203
GSK Investigational Site
New Brunswick, New Jersey, 08901
GSK Investigational Site
Santa Monica, California, 90404
GSK Investigational Site
Tacoma, Washington, 98405
About this study
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
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.
Read the detailed description
This is a Phase I, randomized, double-blind, placebo-controlled, parallel group study designed to estimate the effects of repeated, once daily oral dosing of pazopanib on electrocardiographic parameters with a particular focus on its effect on cardiac repolarization (QTc interval duration) as compared with placebo in subjects with solid tumors. Moxifloxacin, a drug known to cause mild QTc interval prolongation, is included as a positive control to validate the ability of the study to detect a small prolongation in the QTc interval. Digital 12-lead electrocardiograms (ECGs) will be extracted from continuous ECG recordings obtained via a Holter monitor. The effects of pazopanib and moxifloxacin on cardiac repolarization will be compared with placebo.
This study will also assess the pharmacokinetic-pharmacodynamic relationship between plasma concentrations of pazopanib and its metabolites and their effects, if any, on cardiac repolarization, specifically on the QT interval.
- Conditions
- Carcinoma, Renal Cell
- Being tested
- Pazopanib, Placebo for pazopanib, Moxifloxacin, Placebo for moxifloxacin
- Keywords
- GW786034, pazopanib, moxifloxacin, ECG intervals and morphology, QTc, Holter monitor, pharmacokinetics, safety, cancer
- Medical subject headings
- Carcinoma, Renal Cell, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PazopanibDrug
Subjects treated with pazopanib
Placebo for pazopanibOther
Control for comparison with pazopanib
MoxifloxacinDrug
Comparator for pazopanib
Placebo for moxifloxacinOther
Placebo for moxifloxacin
| Study group | Role | What they receive |
|---|---|---|
| Pazopanib | Experimental | Subjects will receive pazopanib during study Receives: Drug: Pazopanib; Drug: Moxifloxacin; Other: Placebo for moxifloxacin |
| Placebo | Other | Placebo as a comparator to pazopanib Receives: Other: Placebo for pazopanib; Drug: Moxifloxacin; Other: Placebo for moxifloxacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 11 days
Secondary outcomes (5)
ECG parameters: RR interval, QT, QTcB, heart rate, PR, QRS intervals and morphology.
Measured: 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.
Measured: 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.
Measured: 11 days
Plasma moxifloxacin concentrations and PK parameters AUC(0-t), AUC(0-∞), Cmax and tmax as data permit.
Measured: 11 days
Safety parameters: AEs, vital signs, ECGs and clinical laboratory assessments.
Measured: 11 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2009 (estimated)
- Study start19 Mar 2009
- Primary completion15 Feb 2010
- Study completion15 Feb 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Renal CellStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00861029
- Sponsor's protocol ID
- 111485
- Status last verified
- Nov 2017
- First submitted
- 12 Mar 2009
- Last updated
- 14 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Heath EI, Infante J, Lewis LD, Luu T, Stephenson J, Tan AR, Kasubhai S, LoRusso P, Ma B, Suttle AB, Kleha JF, Ball HA, Dar MM. A randomized, double-blind, placebo-controlled study to evaluate the effect of repeated oral doses of pazopanib on cardiac conduction in patients with solid tumors. Cancer Chemother Pharmacol. 2013 Mar;71(3):565-73. doi: 10.1007/s00280-012-2030-8. Epub 2013 Jan 24.
PubMed 23344712
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00861029
- Acronym / sponsor ID
- 111485
- Conditions
- Carcinoma, Renal Cell
- Keywords
- GW786034, pazopanib, moxifloxacin, ECG intervals and morphology, QTc, Holter monitor, pharmacokinetics, safety, cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 19 Mar 2009 (actual)
- Primary completion
- 15 Feb 2010 (actual)
- Study completion
- 15 Feb 2010 (actual)
- First posted
- 13 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a Phase I, randomized, double-blind, placebo-controlled, parallel group study designed to estimate the effects of repeated, once daily oral dosing of pazopanib on electrocardiographic parameters with a particular focus on its effect on cardiac repolarization (QTc interval duration) as compared with placebo in subjects with solid tumors. Moxifloxacin, a drug known to cause mild QTc interval prolongation, is included as a positive control to validate the ability of the study to detect a small prolongation in the QTc interval. Digital 12-lead electrocardiograms (ECGs) will be extracted from continuous ECG recordings obtained via a Holter monitor. The effects of pazopanib and moxifloxacin on cardiac repolarization will be compared with placebo.
This study will also assess the pharmacokinetic-pharmacodynamic relationship between plasma concentrations of pazopanib and its metabolites and their effects, if any, on cardiac repolarization, specifically on the QT interval.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pazopanib | Experimental | Drug: Pazopanib, Drug: Moxifloxacin, Other: Placebo for moxifloxacinSubjects will receive pazopanib during study |
| Placebo | Other | Other: Placebo for pazopanib, Drug: Moxifloxacin, Other: Placebo for moxifloxacinPlacebo as a comparator to pazopanib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PazopanibSubjects treated with pazopanib | Drug | Pazopanib |
| Placebo for pazopanibControl for comparison with pazopanib | Other | Placebo |
| MoxifloxacinComparator for pazopanib | Drug | Pazopanib, Placebo |
| Placebo for moxifloxacinPlacebo for moxifloxacin | Other | Pazopanib, Placebo |
Primary outcome
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.
Time frame: 11 days
5 secondary outcomes
ECG parameters: RR interval, QT, QTcB, heart rate, PR, QRS intervals and morphology.
Time frame: 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.
Time frame: 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.
Time frame: 11 days
Plasma moxifloxacin concentrations and PK parameters AUC(0-t), AUC(0-∞), Cmax and tmax as data permit.
Time frame: 11 days
Safety parameters: AEs, vital signs, ECGs and clinical laboratory assessments.
Time frame: 11 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2017.
- Background: PubMed 23344712Heath EI, Infante J, Lewis LD, Luu T, Stephenson J, Tan AR, Kasubhai S, LoRusso P, Ma B, Suttle AB, Kleha JF, Ball HA, Dar MM. A randomized, double-blind, placebo-controlled study to evaluate the effect of repeated oral doses of pazopanib on cardiac conduction in patients with solid tumors. Cancer Chemother Pharmacol. 2013 Mar;71(3):565-73. doi: 10.1007/s00280-012-2030-8. Epub 2013 Jan 24.
- Results for study 111485 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pazopanib and Moxifloxacin in people with Carcinoma, Renal Cell, run by GlaxoSmithKline at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 11 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00861029, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2017.