Pazopanib Versus Sunitinib in the Treatment of Asian Subjects With Locally Advanced and/or Metastatic Renal Cell Carcinoma

Study Overview
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Brief Summary
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This study is being conducted to provide a direct comparison of the efficacy, safety, and tolerabilityfor pazopanib and sunitinib (SUTENT) in the Asian population.

Detailed Description
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The study is designed to evaluate efficacy and safety of pazopanib versus sunitinib for the treatment of Asian subjects with locally advanced and/or metastatic renal cell carcinoma (RCC) enrolled from selected Far-East Asian countries. The primary objective is to evaluate the primary endpoint progression free survival in the enrolled Asian subjects treated with pazopanib versus those treated with sunitinib. The secondary objectives are to evaluate the following secondary endpoints in each treatment arm: objective response rate, duration of response, time to response, overall survival and safety. Subjects will be randomized in a 1:1 ratio to receive either 800mg pazopanib to be administered once daily orally continuous dosing or 50mg sunitinib to be administered in 6-week cycles: 50mg orally daily for 4 weeks followed by 2 weeks off treatment. Subjects are permitted to receive supportive care throughout the study including transfusion of blood and blood products, treatment with antibiotics, anti-emetics, anti-diarrheal agents, analgesics, erythropoietin, or bisphosphonates, when appropriate. The study treatment will continue until subjects experience disease progression, unacceptable toxicity, withdraw consent, or death.

Official Title
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A Study to Evaluate Efficacy and Safety of Pazopanib Versus Sunitinib for the Treatment of Asian Subjects With Locally Advanced and/or Metastatic Renal Cell Carcinoma - A Substudy to VEG108844

Conditions
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Carcinoma, Renal Cell

Intervention / Treatment
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* Drug: Pazopanib
* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Diagnosis of renal cell carcinoma with clear-cell component histology. Received no prior systemic therapy (interleukin-2, interferon-alpha, chemotherapy, bevacizumab, mTOR inhibitor, sunitinib, sorafenib or other VEGF TKI) for advanced or metastatic RCC Locally advanced or metastatic renal cell carcinoma Measurable disease by CT or MRI Karnofsky performance scale status of >=70 Age >=18 years A female is eligible to enter and participate in this study if she is of: non-childbearing or agrees to use adequate contraception. Adequate organ system function Total serum calcium concentration <12.0mg/dL Left ventricular ejection fraction >= lower limit of institutional normal Exclusion Criteria: Pregnant or lactating female (unless agrees to refrain from nursing throughout the treatment period and for 14 days following the last dose of study)-History of another malignancy (unless have been disease-free for 3 years) History or clinical evidence of central nervous system (CNS) metastases (unless have previously-treated CNS metastases and meet all 3 of the following criteria are: are asymptomatic, have had no evidence of active CNS metastases for >=6 months prior to enrolment, and have no requirement for steroids or enzyme-inducing anticonvulsants) Clinically significant gastrointestinal abnormalities including, but not limited to: malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug, active peptic ulcer disease, known intraluminal metastatic lesion/s with suspected bleeding, Inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment Presence of uncontrolled infection Prolongation of corrected QT interval (QTc) > 480 milliseconds History of any one or more of the following cardiovascular conditions within the past 12 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery by-pass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association History of cerebrovascular accident including transient ischemic attack within the past 12 months History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months (unless had recent DVT and have been treated with therapeutic anti-coagulating agents for at least 6 weeks) Poorly controlled hypertension (defined as systolic blood pressure of >=150mmHg or diastolic blood pressure of >=90mmHg). Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer. Evidence of active bleeding or bleeding susceptibility Spitting/coughing up blood within 6 weeks of first dose of study drug Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with patient's safety, obtaining informed consent or compliance to the study Use any prohibited medications within 14 days of the first dose of study medication Use of an investigational agent, including an investigational anti-cancer agent, within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study drug Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors (eg. bevacizumab, sunitinib, sorafenib, etc), or are mTOR inhibitors (eg. temsirolimus, everolimus, etc). Is now undergoing and/or has undergone in the 14 days immediately prior to first dose of study drug, any cancer therapy (surgery, tumor embolization, chemotherapy, radiation therapy, immunotherapy, biological therapy, or hormonal therapy) Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is progressing in severity Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to pazopanib or sunitinib

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pazopanib<br>800 mg administered once daily orally continuous dosing | Drug: Pazopanib<br>* 800 mg administered once daily orally continuous dosing<br>|
| Active Comparator: Sunitinib<br>50 mg sunitinib to be administered in 6-week cycles: 50 mg orally daily for 4 weeks followed by 2 weeks off treatment | Drug: Sunitinib<br>* 50 mg sunitinib to be administered in 6-week cycle: 50 mg orally daily for 4 weeks followed by 2 weeks off treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) | PFS is defined as the interval between the date of randomization and the earliest date of progressive disease (PD), as defined by the Independent Review Committee (IRC), or death due to any cause. The IRC defined PD per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1. Per RECIST, PD is defined as a >=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter (LD) recorded since the treatment started or the appearance of >=1 new lesion. Participants who had neither progressed nor died were censored at the date of the last adequate tumor assessment at the time of the cut-off. | From randomization to the earliest date of disease progression or death (up to 39 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from randomization until death due to any cause. Participants who had not died were censored at the date of the last adequate tumor assessment at the time of the cut-off. | From randomization until death (up to 44 months) | 
| Number of Participants With a Best Response of Confirmed Complete Response (CR) or Confirmed Partial Response (PR) as Assessed by the IRC | The number of participants with evidence of CR (the disappearance of all target lesions. Any pathological lymph node must be less than 10 millimeters [mm] in the short axis) or PR (at least a 30% decrease in the sum of the longest diameters [LD] of target lesions, taking as a reference the Baseline sum LD) was evaluated by an independent review per RECIST, Version 1. | From Baseline until the time of response or the earliest date of disease progression/death (up to 39 months) | 
| Time to Response | Time to response is defined as the time from the start of treatment until the first documented evidence of confirmed CR (the disappearance of all target lesions. Any pathological lymph node must be less than 10 mm in the short axis) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD), whichever comes first. CR and PR were evaluated by an independent review per RECIST, Version 1. | From Baseline until the time of response or the earliest date of disease progression/death (up to 39 months) | 
| Duration of Response (DOR) | DOR is defined as the time from the first documented evidence of confirmed response (CR or PR) until the first documented sign of disease progression (a >=20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of >=1 new lesion) or death, if sooner. CR=the disappearance of all target lesions. Any pathological lymph node must be less than 10 mm in the short axis. PR=at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD. | From the time of response until the earliest date of disease progression/death (up to 38 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SUTENT, GW76034, Sunitinib, Renal cell carcinoma, Pazopanib