Clinical trial NCT01064310
Conditions: Carcinoma, Renal Cell
Keywords: renal cell carcinoma Votrient cancer pazopanib patient preference quality of life
Sponsor: Novartis Pharmaceuticals
Start date: 2010-05-17; Completion date: 2015-11-23
Enrollment: 169 participants; Allocation: RANDOMIZED; Intervention model: 

Brief summary:
This is a randomised, double-blind, cross-over study of pazopanib versus sunitinib in patients with locally advanced or metastatic renal cell carcinoma (mRCC) who have received no prior systemic therapy for advanced or metastatic RCC. Approximately 160 eligible patients will be stratified based on the ECOG performance status (0 vs. 1) and number of metastatic sites of disease (0 and 1 vs. \>=2). The study consists of two treatment periods of 10 weeks with a 2-week wash-out period between the two treatment periods. Patients will receive pazopanib and sunitinib treatment sequentially in a double-blinded fashion. The primary objective of the study is to assess how the tolerability and safety differences between pazopanib and sunitinib translate into patient preference, defined by the patient's stated preference for which drug they may prefer to continue treatment with at end of study. The secondary objectives are to evaluate the reason for patient preference as assessed by a patient preference questionnaire; to evaluate fatigue as assessed by FACIT-Fatigue and quality of life as assessed by EuroQoL EQ-5D; to evaluate dose modifications and time to dose modification; and to evaluate safety.

Detailed description:
This is a randomised, double-blind, cross-over study to evaluate the patient preference of pazopanib versus sunitinib in patients with locally advanced or metastatic RCC who have received no prior systemic therapy for advanced or metastatic RCC. Approximately 160 eligible patients will be stratified based on the ECOG performance status (0 vs. 1) and number of metastatic sites of disease (0 and 1 vs. 2+).

The study consists of two 10-weeks treatment periods with a two-week wash-out period between the treatment periods. Patients will receive pazopanib and sunitinib treatment sequentially. At the end of the second treatment period, patient preference and disease assessment are evaluated and the patients are unblinded. Further treatment is at the discretion of the physician. Further treatment with pazopanib is available within the study. Patients requiring other treatments will complete the study at this point.

Patients will be randomized in a 1:1 ratio to receive blinded (overencapsulated) study drug: either 800mg pazopanib orally for 10 weeks followed by 50mg sunitinib orally for 10 weeks or 50mg sunitinib orally for 10 weeks followed by 800mg pazopanib orally for 10 weeks. A two-week washout period will separate the treatment periods (the medical monitor should be consulted if ongoing AEs need to be resolved and the wash-out period needs to be extended). The regimen for sunitinib is 4 weeks of treatment followed by 2 weeks off treatment. To maintain the double-blind during the two weeks off drug for patients on sunitinib ('Treatment Holiday'), patients will be taking matching placebo. No study drug will be taken during the wash-out period in either arm.

Following the two-week wash-out period and disease assessment, all patients are planned to cross over to the second treatment. Patients will be informed of their disease assessment result and any patient that wishes to come off study at this point due to a very significant response, defined as more than a 50% reduction in tumour size (or complete response if non-measurable disease), will have the option to be unblinded to continue with whichever treatment they were on, however each patient case will need to be discussed with the medical monitor prior to unblinding. Patients who were on sunitinib will leave the study and continue treatment outside the study. Patients who were on pazopanib will continue on pazopanib within the pazopanib open-label part of the study. Conversely, should a patient have a very significant response and wish to cross over or complete the study, this must be documented in the patients notes.

Patients crossing over with progressive disease will follow the same visit schedule and assessments and investigators will have the option for these patients to be unblinded or not. The patients' preference will be collected and analysed but will not contribute to the primary, but an exploratory analysis because of the bias caused by progressing on the first treatment. Even if unblinded, patients may continue to receive the second treatment and may receive open label pazopanib after the second treatment within the study if they did not progress on pazopanib.

Patients who withdraw from treatment due to unacceptable toxicity or progression during the first treatment period will cross-over directly to the second treatment following a 2-week wash-out period.

Actual further treatment at the end of the study will be at the discretion of the investigator taking into account both disease assessments results, laboratory results and the patient preference. Choice and rationale for continuing treatment will be documented.

Patients who did not progress on pazopanib and who prefer to continue with pazopanib may continue on pazopanib and will be followed up for safety until the patient comes off pazopanib due to disease progression, toxicity, death or patient choice, which ever is the earliest.

Those patients that may benefit from further treatment with sunitinib for the same reasons as above will receive it off study and will not be followed up, as will patients who receive any other treatment.

Patients are permitted to receive supportive care throughout the study including transfusion of blood and blood products, treatment with antibiotics, anti-emetics, anti-diarrhoeal agents, analgesics, erythropoietin or bisphosphonates, when appropriate. The study treatment will continue until the end of the two treatment periods or unacceptable toxicity or consent withdrawal or death, whichever occurs first.

The patient preference will be ascertained prior to the second disease assessment result being shared with the patient to avoid bias.

Arms: arm 1: 800mg pazopanib orally for 10 weeks followed by 50mg sunitinib orally for 10 weeks arm 2: 50mg sunitinib orally for 10 weeks followed by 800mg pazopanib orally for 10 weeks
Interventions: intervention 1: pazopanib intervention 2: sunitinib
Intervention descriptions: intervention 1: oral anti-angiogenic treatment intervention 2: oral anti-angiogenic treatment

Protocol documents: