Surf: Open label, randomized multi-centre phase II study to assess the efficacy and tolerability of sunitinib by dose administration regimen (dose modification or dose interruptions) in patients with advanced or metastatic renal cell carcinoma (mRCC)

Background

Sunitinib is a tyrosine kinase inhibitor approved in first line mRCC setting at the dose of 50 mg daily for 4 weeks followed by a pause of 2 weeks (schedule 4/6 50mg). Due to toxicity this schedule 4/6 50mg can induce up to 50% of sunitinib dose modification (reduction and/or interruption). Current recommendation in such case is to reduce the dose to 37.5 mg per day (schedule 4/6 37.5mg). Retrospective and prospective data highlight an alternative schedule: 2 weeks of treatment followed by one week of pause (schedule 2/3 50mg). SURF trial is set up to compare schedule 2/3 50mg to schedule 4/6 37.5mg when toxicity occurs.

Trial design

SURF [NCT02689167] is a prospective, randomized, open-label phase IIb study. Patients are included at sunitinib initiation while receiving schedule 4/6 50mg according to the Marketing Authorization Indication. When a dose adjustment of sunitinib is required, patients are randomized between arm A with schedule 4/6 37.5mg and arm B with schedule 2/3 50mg. Main eligibility criteria are: patients with locally advanced inoperable or mRCC who are starting first line treatment with Sunitinib; with histologically or cytologically confirmed renal cancer clear cell variant or with a clear cell component and with Karnofsky performance status ≥ 70%. Primary objective is to assess the median duration of sunitinib treatment (DOT) in each group. Key secondary objectives are progression-free survival, overall survival, time to randomization, objective response rate, safety, sunitinib dose intensity, quality of life and the description of main drivers triggering randomization. We hypothesized that schedule 2/3 50mg would result in an improvement in median DOT from 6 months to 8.5 months. It was estimated that 112 patients would be need in each arm during 24 months. In order to take account the possibility of treatment discontinuation before randomization 248 patients are necessary. Study start was in February 2016; at April 2016, 5 patients were enrolled. Update on trial enrolment kinetics will be shown during ESMO congress.

Clinical trial identification

NCT02689167; Trial protocol number 2015-002575-16

Legal entity responsible for the study

University Hospital of Besancon, France

Funding

Pfizer

Disclosure

G. Mouillet: Membership on an advisory board: Pfizer, Novartis Corporate-sponsored research: Pfizer, Novartis. F. Bonnetain: Amgen Celgene Roche (plus grant) Novartis (plus grant) Integragen Janssen Ipsen Merck Serono Nestlé Santé Bayer Bms Chugai Eisai. A. Thiery-Vuillemin: Consulting: Pfizer, Novartis Funding: Pfizer. All other authors have declared no conflicts of interest.