Open Label, Randomized, Multicenter Phase II Study of a Combination of Torisel® (Temsirolimus) and Avastin® (Bevacizumab) Versus Sutent® (Sunitinib) and Versus a Combination of Avastin® (Bevacizumab) and Roféron® (Interferon Alpha-2a) in First-line Treatment of Patients With Metastatic Renal Cell Carcinoma.
This is a phase II, open label, randomized, parallel group, multicenter study evaluating
first-line treatment of patients with metastatic renal cancer using a combination of
Torisel® administered intravenously as 25 mg every week and Avastin® administered
intravenously as 10 mg/kg every 2 weeks.
Two standard arms with either Sutent® (given orally as 50 mg once daily during 4 weeks,
followed by 2 weeks off) or a combination of Avastin® (administered intravenously as 10
mg/kg every 2 weeks) and Interferon (IFN, administered subcutaneously as 9 MU three times a
week) will be used to validate the results obtained in the experimental arm (randomization
eliminates selection biases), and to assess Sutent® efficacy rate on a more representative
population than in Motzer's trial (Motzer NEJM 2007).
The study is not designed to provide head-to-head comparisons between the experimental arm
(Avastin® + Torisel®) and the two standard arms (Sutent® and IFN + Avastin®). Randomization
will be used as a tool for allocating patients evenly into the 3 treatment arms to ensure
proper balance of prognostic factors. If the progression-free rates observed in randomly
assigned control patients are inconsistent with historical data, it may be a warning that
the results observed for the experimental arm should be viewed with caution. Patients will
be randomly assigned to either option in a 2:1:1 ratio (half less patients in the standard
arms used only as historical comparators), and stratified according to inclusion center and
performance status (ECOG PS 0 vs. 1 vs. 2).
In the absence of severe toxicity, treatment will be continued until documented progression
of the disease (RECIST criteria). Toxicity will be evaluated throughout the treatment period
and until disappearance or stabilization of the side effect(s). In case of progression, each
investigator makes his/her own treatment decisions, provided that all anti-cancer treatments
given to the patients within the frame of the study are reported, as well as their results.
Response rates will be assessed between weeks 11-12, 23-24, 35-36, 47-48 in the first year
(corresponding to 2 cycles of Sutent®) and every 3 months afterwards until treatment stop,
or until patient death or end of clinical data collection.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
at 48 weeks post-treatment
Sylvie NEGRIER, MD, PhD
Centre Leon Berard
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)