Clinical Trial to Assess the Importance of Nephrectomy

Study Overview
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Brief Summary
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The study compare the standard treatment with nephrectomy + sunitinib to treatment with sunitinib alone without nephrectomy. This study will be the first trial on this competitive context

Detailed Description
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The 2 previous studies on the impact of nephrectomy (EORTC, SWOG) in metastatic renal cell carcinoma have justified recommendation to initial nephrectomy for patients presenting with metastatic renal cell carcinoma. But these studies were performed at the time of immunotherapy. The objective is Evaluation of the importance of nephrectomy in patients with metastatic renal cell carcinoma treated with sunitinib (AA) Arm A : Nephrectomy followed by Sunitinib Arm B : Sunitinib alone Sunitinib will be administrated orally daily for 4 weeks followed by a 2 week rest( schedule 4/2), 6 weeks are considered as a cycle The starting dose will be 50 mg daily with provision for dose reduction based on tolerability Patient will be treated until disease progression or unacceptable toxicity occurrence or withdraw.

Official Title
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Randomized Phase III Trial Evaluating the Importance of Nephrectomy in Patients Presenting With Metastatic Renal Cell Carcinoma Treated With Sunitinib

Conditions
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Metastatic Renal Cell Carcinoma

Intervention / Treatment
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* Procedure: Nephrectomy
* Other: Sunitinib alone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 18 years ECOG Performance Status 0 - 1 Biopsy (primary tumour or metastases) confirming the diagnosis of clear cell carcinoma Documented metastatic disease Absence of prior systemic treatment for kidney cancer including AA Tumour amenable to nephrectomy (partial or total) in the opinion of the patient's urologist. Patients presenting with an inferior vena cava thrombosis can be included. Patients for which the indication of Sunitinib is considered according to the recommendations rules given by national health authorities of participating countries. The prescription of Sunitinib in the circumstances of the study is considered as a standard treatment. Platelets > or = 100 x 109/L, haemoglobin >or = 9 g/dl, neutrophils >or = 1.5 x 109/L; Bilirubin < or = 2 mg/dL, aspartate transaminase (ASAT) and alanine transaminase (ALAT)< or = 2.5 times the upper normal limit (UNL) or < or = 5 times UNL for patients with liver metastases Patients of child bearing age should use contraceptive methods Patient able to follow the procedures outlined in the protocol as far as the planning of visits and examinations are concerned. Life expectancy ≥ 3 months Written informed consent Patient without brain metastases or with radiotherapy or surgery treated brain metastases without progression into 6 weeks and non treated by corticoid Patient non treated by anticoagulants excepted HBPM Exclusion Criteria: Prior systemic treatment for kidney cancer (including Anti Angiogenic) Bilateral kidney cancer Pregnant or breast feeding women Acute coronary syndrome or episode of myocardial infarction or severe or unstable angina within the last 6 months as well as severe diabetes with severe peripheral arteriopathy or deep phlebitis not treated with low molecular weight heparin or arterial thrombosis within the last 3 months Patients being treated with antivitamin K with curative intent (please note that patients being treated with low molecular weight heparin can be included) Medical, general or psychiatric difficulties which, in the opinion of the Investigator, would make it inappropriate for trial entry Symptomatic or untreated brain metastases (patients with brain metastases that have been treated by radiotherapy or surgery and have stable disease within 6 weeks, and are not requiring treatment with corticosteroids can be included) Previous history of gastric disease or malabsorption, syndrome compromising the absorption of Sunitinib Experimental treatment within the 28 days preceding inclusion Other cancer within the previous 5 years (except for insitu skin carcinoma and treated localised prostate cancer with undetectable PSA) Patient has received treatment with IV biphosphonate

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Nephrectomy + sunitinib | Procedure: Nephrectomy<br>* Current surgery<br>|
| Experimental: B<br>Sunitinib alone | Other: Sunitinib alone<br>* Sunitinib alone without nephrectomy<br>* Other names: Sunitinib alone without nephrectomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is overall survival. |  | starting at 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response (complete or partial) is evaluated according to RECIST 1.1 criteria |  | Starting at 4 months | 
| Clinical benefit (complete response, partial or stable for at least 12 weeks). |  | Starting at 4 months | 
| Progression-Free Survival |  | Starting at 4 months | 
| Non-compliance to Sunitinib treatment is evaluated in arm A (nephrectomy + sunitinib) as the percentage of patients not starting sunitinib treatment within 6 weeks after nephrectomy |  | Starting at 4 months | 
| Non-compliance to sunitinib treatment is evaluated in arm B (sunitinib alone) as the percentage of patients needing nephrectomy |  | Starting at 4 months | 
| Post operative morbidity is evaluated as the percentage of deaths within 30 days following nephrectomy |  | Starting at 4 months | 

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