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

Phase 2

Completed

Conditions: Carcinoma, Renal Cell

Interventions: Drug: Pazopanib
Drug: Sunitinib

Registration Number: NCT01147822

Lead Sponsor: Novartis Pharmaceuticals

Brief Summary: This was a randomized, open label, parallel group, Phase II study to evaluate the efficacy and safety of pazopanib compared to sunitinib in Asian subjects with advanced renal cell carcinoma (RCC) who have not received prior systemic therapy for advanced or metastatic RCC.

Detailed Description: Study VEG113078 is a substudy of Study VEG108844 (NCT00720941). Due to the projected limited enrollment of Asian participants into Study VEG108844, Study VEG113078 was designed to evaluate the efficacy and safety of pazopanib versus sunitinib for the treatment of Asian participants enrolled from selected Far-East Asian countries. The data for Study VEG113078 was pooled at the same time as the main study VEG108844 (NCT00720941). The subjects were centrally randomized in 1:1 ratio to receive open label study medication of either pazopanib 800mg to be administered once daily orally continuous dosing or sunitinib 50mg to be administered in 6-week cycles: 50mg orally daily for 4 weeks followed by 2 weeks off treatment. Subjects were 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 continued until subjects experience disease progression, unacceptable toxicity, withdraw consent, or death.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 367

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pazopanib	Pazopanib	800 mg administered once daily orally continuous dosing
Sunitinib	Sunitinib	50 mg sunitinib to be administered in 6-week cycles: 50 mg orally daily for 4 weeks followed by 2 weeks off treatment

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	From randomization until the earliest date of disease progression or date of death from any cause, assessed up to approximately 24 months (Primary analysis cut-off date = 21-May-2012) at the same time as the main study VEG108844 (NCT00720941).	PFS was 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 recorded since the treatment started or the appearance of \>=1 new lesion.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR) as Assessed by Independent Review	From randomization until date of radiographic progression, assessed up to approximately 24 months (Primary analysis cut-off date = 21-May-2012) at the same time as the main study VEG108844 (NCT00720941).	Overall Response Rate (ORR) was defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). ORR was based on RECIST 1.1 response for patients with measurable disease at baseline per central review assessment.
Overall Survival (OS)	From randomization until date of death from any cause, assessed up to 40 months (Final OS analysis cut-off date = 30-Sep-2013) at the same time as the main study VEG108844 (NCT00720941).	Overall Survival (OS) was defined as the time (in months) from the date of randomization to the date of death due to any cause. If the patient was not known to have died, then OS was censored. The censoring date was date of the last study visit, or contact, until the cut-off date. The cut-off date was not used for last contact date, unless the patient was seen or contacted on that date.
Duration of Response (DOR)	From the date of the first documented response (CR or PR) to the date of first documented progression, assessed up to approximately 24 months (Primary analysis cut-off date = 21-May-2012) at the same time as the main study VEG108844 (NCT00720941).	DOR was defined as the time from the first documented evidence of 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 and non-target lesions. PR=at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the Baseline sum LD.
Time to Response	From randomization until date of radiographic progression, assessed up to approximately 24 months (Primary analysis cut-off date = 21-May-2012) at the same time as the main study VEG108844 (NCT00720941).	Time to response was defined as the time from the start of treatment until the first documented evidence of CR (the disappearance of all target and non-target lesions) 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.