Comparison of Sequential Therapies With Sunitinib and Sorafenib in Advanced Renal Cell Carcinoma

Study Overview
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Brief Summary
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The clinical benefits of sunitinib and sorafenib have been demonstrated in patients with cytokine-refractory metastatic renal cell carcinoma. Sunitinib has also been shown to improve progression free survival and overall survival in a comparative study with interferon-alpha. When sunitinib is used as first-line molecular-targeted therapy, switching to sorafenib is one of the treatment options after disease progression. Reversely, when sorafenib is used as first-line molecular-targeted therapy, sunitinib is used as second-line therapy. The goal of cancer treatment is cure, and if cure is not possible, it is to prolong survival. In this study, sunitinib or sorafenib will be administered as first-line molecular-targeted therapy and treatment switched to the other test drug, sorafenib or sunitinib, when disease progression is detected to assess which treatment sequence produces longer progression free survival and offers a better safety profile (causing fewer adverse events). The purpose of this trial is to compare progression free survival of first line sunitinib versus sorafenib, and that of two treatment sequences, i.e. sunitinib followed by sorafenib versus sorafenib followed by sunitinib.

Official Title
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Randomized Comparison of Sequential Therapies With Sunitinib and Sorafenib in Advanced Renal Cell Carcinoma

Conditions
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Metastatic Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Sorafenib-sunitinib
* Drug: Sunitinib-sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 20-80 years old, both inclusive ECOG performance status of 0, 1, or 2 MSKCC risk of favorable or intermediate Histologically confirmed renal cell carcinoma No ischemic heart disease Laboratory findings meet the following criteria: Respiratory function: %VC, 80% and FEV1.0,70% Hematology: white blood cell count4,000/mm3, platelet count100,000/mm3 Clinical chemistry: GOT and GPT within the normal range of each medical institution; total bilirubin <1.5 x ULN Serum creatinin <2.0mg/dl, blood urea nitrogen (BUN) <25mg/dl Echocardiographic estimation of left ventricular ejection fraction is higher than the lower limit of reference range of each medical institution. Exclusion Criteria: History of any other malignancy Central nervous system metastases. However, patients who remain asymptomatic, have no new or enlarging lesion in the CNS within 6 months of enrollment in this study, and require no corticosteroids may be enrolled. History of cardiac infarction, unstable angina, congestive heart failure, or symptomatic peripheral vascular disease within 12 months of enrollment History of cerebrovascular disorder including transient ischemic attack (TIA) Pregnancy or possible pregnancy at any time during the study Ongoing grade 2 adverse event prior treatment Prior treatment with any anticancer therapy including cytokine therapy such as interferon-alpha and interleukin-2 Prior treatment with mTOR inhibitor Prior treatment with sunitinib or sorafenib Treatment with an test drug in a clinical research within 4 weeks of enrollment in this study

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sorafenib-sunitinib<br>Sorafenib is first line treatment followed by sunitinib. | Drug: Sorafenib-sunitinib<br>* sorafenib 400mg b.i.d. followed by sunitinib treatment when progression is observed<br>|
| Active Comparator: Sunitinib-sorafenib<br>Sunitinib is first line treatment followed by sorafenib. | Drug: Sunitinib-sorafenib<br>* sunitinib 50mg q.d. 4 weeks on two weeks off followed by sorafenib treatment when progression is observed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival in first-line treatment | From date of randomization until the date of first documented progression of the first line treatment or date of death from any cause, whichever came first, assessed up to 36 months. | Time of progression in first line treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total progression free survival (PFS) in first-line and second-line treatments | From date of randomization until the date of first documented progression of the second line treatment or date of death from any cause, whichever came first, assessed up to 36 months. | Time of progression in second line treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal cell carcinoma, sorafenib, sunitinib, crossover