Clinical trial NCT01235962
Conditions: Renal Cell Carcinoma (RCC) Cancer
Keywords: anti-angiogenic agent renal cell carcinoma pazopanib adjuvant therapy VEGFR inhibitor localized or locally advanced renal cell carcinoma (RCC) following nephrectomy advanced RCC Cancer
Sponsor: Novartis Pharmaceuticals
Start date: 2010-11-30; Completion date: 2019-04-15
Enrollment: 1538 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This randomized Phase III study is to evaluate whether pazopanib compared with placebo can prevent or delay recurrence of kidney cancer in patients with moderately high or high risk of developing recurrence after undergoing kidney cancer surgery.

Detailed description:
The primary objective of this ongoing study was to evaluate DFS with pazopanib 600 mg daily initial dose as compared with placebo as adjuvant therapy for subjects with localized/locally advanced RCC following nephrectomy.

Subjects with locally recurrent renal cell carcinoma (RCC), bilateral RCC, or history of another malignancy were excluded from enrolling in the study.

The study was comprised of three successive study periods: 1) the Screening/Baseline period, 2) the study treatment period, and 3) the DFS /OS follow-up period. The Screening/Baseline period had a maximum duration of 12 weeks from the date of nephrectomy to the date of randomization.

After a subject met all the eligibility criteria and completed all the required baseline assessments, the subject was randomized in a 1:1 ratio to receive once daily blinded treatment with either pazopanib 600 mg as initial dose or matching placebo based on pre-defined stratification factors.

Subjects received continuous daily treatment until completion of the 12-month treatment period, disease recurrence, or unacceptable toxicity/intolerance. Subsequent adjuvant therapies for RCC were not allowed. During the study treatment and DFS follow-up periods, subjects received routine safety and efficacy assessments.

The study treatment period was 12 months. Subjects received continuous daily treatment until completion of the 12 month treatment period, disease recurrence, or unacceptable toxicity/intolerance. Subsequent adjuvant therapies for RCC were not allowed.

All subjects, regardless of study treatment status (i.e. premature discontinuation or completion of the 12-month treatment), were to be followed with routine imaging assessments and remain blinded until objective evidence of disease recurrence was obtained or until the study achieved the required number of events for the primary endpoint of DFS (319 events). After objective evidence of disease recurrence was obtained, subjects could be unblinded and received the first-line treatment for metastatic RCC per local standard of care.

All subjects were off treatment for at least 4 years at the end of study.

Arms: arm 1: Pazopanib oral agent, administered at 600 mg daily initial dose for 8-12 weeks. Dose can be escalated to 800 mg daily based on safety evaluation. Complete treatment is 12 months. Dose can be reduced, interrupted or discontinued due to adverse events or intolerance. arm 2: placebo matching pazopanib 200 mg tablets, administered at 600 mg daily initial dose for 8-12 weeks. Dose can be escalated to 800 mg daily based on safety evaluation. Complete treatment is 12 months. Dose can be reduced, interrupted or discontinued due to adverse events or intolerance.
Interventions: intervention 1: pazopanib intervention 2: placebo intervention 3: pazopanib intervention 4: placebo
Intervention descriptions: intervention 1: Pazopanib monohydrochloride salt was supplied as aqueous, film-coated tablets containing 200 mg of the free base. The 200 mg tablets were oval-shaped and white in color. intervention 2: Placebo matching pazopanib was supplied as aqueous, film-coated tablets containing 200 mg of the free base. The 200 mg tablets were oval-shaped and white in color. intervention 3: Pazopanib 600 mg daily initial dose for 8-12 weeks, dose can be escalated to 800 mg daily based on safety evaluation. intervention 4: placebo matching pazopanib daily initial dose for 8-12 weeks, dose can be escalated to 800 mg daily based on safety evaluation.

Protocol documents: