VEG111485: A Phase I, Randomized, Double-Blinded, Placebo-Controlled Study to Evaluate the Effect of Repeat Oral Doses ofPazopanib (GW786034) on Cardiac Conduction in Subjects withSolid Tumors
- Male or female, age 18 years or older, at the time of signing of the informed
- 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
- Subject is a woman of non-childbearing potential or willing to use acceptable
- Subject is a man with a female partner of childbearing potential agrees to use
- 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.
- 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
- 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.