To evaluate efficacy and safety of pazopanib compared to placebo in patients with locally advanced and/ or metastatic renal cell carcinoma (RCC). Approximately 350-400 eligible patients will be stratified and randomized in a 2:1 ratio to receive either 800 mg pazopanib once daily or matching placebo. The study treatment will continue until patients experience disease progression, unacceptable toxicity or death. Primary objective of the study is to evaluate and compare the two treatment arms for progression-free survival. Principal secondary objective is to evaluate and compare the two treatment arms with respect to overall survival. Other objectives are overall response rate \[complete response (CR) + partial response (PR)\], rate of CR + PR + 6 months stable disease, and the incidence, severity and causality of adverse events and serious adverse events. Safety and efficacy assessments will be regularly performed on all patients. An Independent Data Monitoring Committee will be established to monitor safety during the course of the study and to evaluate interim efficacy data on overall survival.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
435
Oral pazopanib tablet 800 mg once daily continuously
matching placebo (800 mg tablet) once daily
GSK Investigational Site
Capital Federal, Buenos Aires, Argentina
GSK Investigational Site
Córdoba, Córdoba Province, Argentina
GSK Investigational Site
Rosario, Santa Fe Province, Argentina
GSK Investigational Site
Quilmes, Argentina
GSK Investigational Site
San Miguel de Tucumán, Argentina
Progression-free Survival
Progression-free survival (PFS) is defined as the interval between the date of randomization and the earliest date of disease progression or death due to any cause. Assessments of progression and non-progression were made by an independent imaging review committee (IRC) for the primary analysis.
Time frame: Randomization until progression (up to 2 years)
Overall Survival
Overall survival is defined as the time from randomization until death. The length of this interval was estimated as the date of death minus the date of randomization plus 1 day. Participants who were still alive at the time of analysis were censored.
Time frame: Randomization until death (up to 2 years)
Overall Response
Overall response is the number of participants who had a complete response (CR) or a partial response (PR). Per RECIST: CR, all detectable tumor has disappeared; PR, a \>=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the Baseline sum, no worsening of non-TLs, and no new lesions; Progressive disease (PD), a \>=20% increase in TLs, clearly worsening of non-TLs, or emergence of new lesions; Stable Disease, small changes that do not meet previously given criteria. IRC, independent review committee.
Time frame: Baseline until either response or progression (up to 2 years)
Participants With Complete Response, Partial Response, or 6 Months of Stable Disease
This is similar to overall response rate, but also includes participants who had stable disease for at least 6 months. Per Response Evaluation Criteria In Solid Tumors (RECIST): CR, all detectable tumor has disappeared; PR, a \>=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the Baseline sum; Stable Disease, small changes that do not meet previously given criteria; Progressive Disease, a \>=20% increase in target lesions. IRC, independent review committee.
Time frame: Baseline until 6 months post-Baseline or progressive disease
Duration of Response
Duration of response is defined as the time from first observation of response until progression of disease or death.
Time frame: Time from response until progression (up to 2 years)
Time to Response as Assessed by an Independent Review Committee (IRC) and the Investigator
Time to response is defined as the time from randomization until the first documented evidence of complete response (all detectable tumor has disappeared) or partial response (a \>=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the Baseline sum) (whichever status was recorded first).
Time frame: Randomization until CR or PR (assessed for up to 2 years)
Adjusted Mean Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire Core 30 (EORTC QLQ C-30) Score at Weeks 6, 12, 18, 24, and 48
The EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer participants. The analyses for EORTC QLQ-C30 were focused on global health status/Health-Related Quality of Life (HRQOL) scores on the questionnaire. The scores (from 1 \[very poor quality of life\] to 7 \[excellent quality of life\]) for these two questions were averaged and then transformed to a 0 - 100 scale (based on published methods) prior to analysis of change from Baseline.
Time frame: Baseline and Weeks 6, 12, 18, 24, and 48
Adjusted Mean Change From Baseline in the Index Score of the EQ-5D (EuroQoL [Quality of Life]-5D) Questionnaire at Weeks 6, 12, 18, 24, and 48
The EQ-5D is comprised of a 5-item health status measure and a visual analogue rating scale, and measures mobility, self-care, usual activities, pain, discomfort, and anxiety/depression. Responses to each of the 5 health states are measured on a 3-point scale (no, moderate, and extreme problems). Scoring of the EQ-5D yields an index-based summary score (Index), through application of societal weights, and a VAS score (VAS). Index is interpreted on a continuum from 1.0 (best possible health) to 0 (represents dead), to some health sates being worse than dead (\<0).
Time frame: Baseline and Weeks 6, 12, 18, 24, and 48
Adjusted Mean Change From Baseline in the Visual Analog Scale (VAS) Score of the EQ-5D (EuroQoL [Quality of Life]-5D) Questionnaire at Weeks 6, 12, 18, 24, and 48
The EQ-5D is comprised of a 5-item health status measure and a visual analogue rating scale, and measures mobility, self-care, usual activities, pain, discomfort, and anxiety/depression. Responses to each of the 5 health states are measured on a 3-point scale (no, moderate, and extreme problems). Scoring of the EQ-5D yields an index-based summary score (Index) and a VAS score (VAS), obtained from participant's self-reports of their health on a VAS thermometer scale. The EQ-5D VAS ranges from 0% (worst imaginable health state) to 100% (best imaginable health state).
Time frame: Baseline and Weeks 6, 12, 18, 24, and 48
Plasma Pazopanib Concentrations Before Dosing and at 2, 4, and 8 Hours After Dosing on Day 1 and Week 3
The concentration of pazopanib in the plasma was measured.
Time frame: Day 1 and Week 3
Baseline Expression Levels of the Indicated Target Proteins in Pazopanib- and Placebo-treated Participants
Baseline plasma samples were obtained from participants and were tested for the indicated cytokine and angiogenesis factors. Protein levels were determined using the Searchlight multiplex system based on chemiluminescence.
Time frame: Baseline
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
GSK Investigational Site
St Leonards, New South Wales, Australia
GSK Investigational Site
Waratah, New South Wales, Australia
GSK Investigational Site
Hobart, Tasmania, Australia
GSK Investigational Site
Heidelberg, Victoria, Australia
GSK Investigational Site
Wodonga, Victoria, Australia
...and 89 more locations