A Randomised Double-blind Cross-over Patient Preference Study of Pazopanib Versus Sunitinib in Treatment naïve Locally Advanced or Metastatic Renal Cell Carcinoma.
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
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
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.
Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Number of Participants With Preference for Pazopanib Versus Sunitinib as Assessed by the Patient Preference Questionnaire (PPQ)
The PPQ is used to measure participants' preference for pazopanib or sunitinib for renal cell carcinoma management and is used to determine a participant's preference for 1 of the 2 drugs given in the 2 double-blind treatment periods. Participants were asked to select 1 of the following: 1. prefer the drug taken as the first treatment; 2. prefer the drug taken as the second treatment; or 3, no preference. Those participants who indicated a preference were asked to select the factors that had an influence on their treatment preference, as well as the most important reason for their preference.
End of treatment of both study drugs (maximum of 22 weeks)
GSK Clinical Trials
Finland: Finnish Medicines Agency