Sorafenib in Elderly Patients With Metastatic Renal Cell Carcinoma (SERCC Study) Impact of Adverse Events Management in Elderly mRCC Patients Treated With Sorafenib
Rationale of the present study For several decades, the systemic management of metastatic
renal cell cancer (mRCC) was confined to the use of interferon (IFN) and interleukin-2
(IL-2). Recently, options for the medical management of mRCC have been improved through the
introduction of agents targeting tumour angiogenesis or intracellular pathways mediating
growth and proliferation. Among these agents are the small molecule inhibitors sorafenib
(Nexavar), sunitinib (Sutent), temsirolimus (Torisel) and everolimus, and the monoclonal
antibody bevacizumab (Avastin). All these targeted agents have been shown significantly to
extend progression-free or overall survival or both when compared with placebo or IFN
therapy in the treatment of mRCC.
Adverse events are commonly observed in clinical practice by using these small molecule
inhibitors in mRCC patients. Concerning the use of bevacizumab the most commonly observed
adverse events are hypertension, proteinuria, bleeding and thrombosis. For sunitinib the
most frequent adverse events include hand-foot syndrome, stomatitis, diarrhea, fatigue,
hypothyroidism and hypertension.
Most common adverse events with sorafenib are hand foot skin reaction (HFSR) rash,
desquamation, fatigue, diarrhea, nausea, hypothyroidism and hypertension.Several studies and
recommendations have been published in order to suggest how to manage sorafenib adverse
reactions and in particular the HFSR.
The aim of this study is to evaluate if patients education programs for the prevention of
dermatological events (HFSR, rash, desquamation) can reduce the onset these adverse events
(all grades). The reduction of dermatological adverse effects would concomitantly limit the
frequencies of sorafenib dose reduction and interruptions in mRCC patients not suitable for
cytokines or anti-angiogenesis (bevacizumab or sunitinib) therapy as first line treatment.
Treatment Administration Sorafenib will be orally administered at a daily dose of 400 mg
taken twice daily without food, at least one hour before or two hours after eating. Four
weeks of treatments will be considered as a cycle. Each patient enrolled in the study will
received medications for topical therapy. Dermatological medications will be provided free.
In case of toxicities, dose reduction/interruption is permitted according to the flow
In case of disease progression, or unacceptable toxicities Sorafenib administration will be
The patient will be considered "out of treatment" if Sorafenib intake is stopped for more
than 30 consecutive days and the patient will be considered for survival.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary aim of this trial is the evaluation of the efficacy of a patient education program in the reduction of HFSR
The primary aim is to determine the efficacy of the patient education program in reducing the incidence of HFSR(all grades).The efficacy is measured in terms of percentage of HFSR-free.Simon's methods will be used to calculate sample size(Simon R,1989).Considering the optimal two-stage design for phase II,considering a difference p1-p0=20% and fixing error probabilities(alfa=0.05 and beta=0.20),the number of patients for the first step is 16.The trial will be terminated if less than 7 HFSR-free patients will be seen.Otherwise the accrual will continue up to a total of 46 patients.
From enrollment in the study until 1 year
Lucia Fratino, oncologist
Centro di Riferimento Oncologico - IRCCS - Aviano
Italy: The Italian Medicines Agency