Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer

Study Overview
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Brief Summary
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RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving sunitinib malate before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving sunitinib malate after surgery may kill any tumor cells that remain after surgery. It is not yet known whether undergoing immediate surgery or surgery after sunitinib malate is more effective in treating patients with metastatic kidney cancer. PURPOSE: This randomized phase III trial is studying immediate surgery to see how well it works compared with surgery after sunitinib malate in treating patients with metastatic kidney cancer.

Detailed Description
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OBJECTIVES: To determine if immediate versus deferred nephrectomy has an effect on disease control in patients with resectable, synchronous, metastatic renal cell carcinoma treated with sunitinib malate. To identify potential response criteria based on histopathology and molecular research on tumor tissue. OUTLINE: This is a multicenter study. Patients are stratified according to WHO performance status (0 vs 1), number of metastatic sites (1 vs 2 or more), and institution. Patients are randomized to 1 of 2 treatment arms. Arm I (immediate nephrectomy): Patients undergo cytoreductive nephrectomy. Beginning 4 weeks after surgery, patients receive oral sunitinib malate once daily on days 1-28. Treatment with sunitinib malate repeats every 6 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Arm II (deferred nephrectomy): Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. About 1 day after completion of sunitinib malate, patients undergo cytoreductive nephrectomy. Patients then receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 6 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Some patients undergo tumor tissue collection at baseline and at time of surgery to assess possible differences in gene expression. Patients also undergo blood sample collection periodically to evaluate the potential impact of serum proteins on the clinical outcome. Samples are then stored for future studies. After completion of study treatment, patients are followed periodically.

Official Title
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Randomized Phase III Trial Comparing Immediate Versus Deferred Nephrectomy in Patients With Synchronous Metastatic Renal Cell Carcinoma

Conditions
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Kidney Cancer

Intervention / Treatment
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* Procedure: timing of surgery
* Genetic: gene expression analysis
* Other: biologic sample preservation procedure
* Other: laboratory biomarker analysis
* Procedure: therapeutic conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed renal cell cancer (RCC) Clear-cell subtype with a resectable asymptomatic in situ primary Asymptomatic primary is defined as the absence of symptoms* which can be exclusively assigned to the primary tumor such as flank pain and/or gross hematuria necessitating blood transfusion NOTE: *Para-neoplastic symptoms cannot be assigned to the primary tumor alone in metastatic disease, they are not included in this definition. No symptomatic primary tumor necessitating nephrectomy Resectable primary tumor Bulky locoregional lymph node metastases larger than the primary tumor allowed provided resectability of the lymph nodes is surgically feasible Metastatic RCC Distant metastases are not completely resectable at the time of surgery or during an additional intervention No multiple distant lesions at one site No bone-only metastases Measurable disease, both primary and metastatic, according to RECIST 1.1 criteria Planning to receive sunitinib malate as background therapy Patients with > 3 of the following surgical risk factors are not eligible: Serum albumin CTCAE v 4.0 grade 2 or worse Serum LDH > 1.5 times upper limit of normal Liver metastases Symptoms at presentation due to metastases Retroperitoneal lymph node involvement Supra-diaphragmatic lymph node involvement Clinical stage T3 or T4 disease No clinical signs of CNS involvement PATIENT CHARACTERISTICS: See Disease Characteristics WHO performance status 0-1 Life expectancy > 3 months WBC > 3.0 x 10^9/L Platelet count > 100 x 10^9/L Hemoglobin > 10.0 g/dL PT/PTT or INR ≤ 1.2 times upper limit of normal (ULN) Bilirubin ≤ 1.5 times ULN ALT ≤ 2.5 times ULN (≤ 5 times ULN if liver lesions) Serum calcium < 10.0 mg/dL Calculated or measured creatinine clearance > 30 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception 2 weeks before and during study treatment LVEF normal by MUGA scan or ECHO 12-lead ECG normal No serious cardiac illness (myocardial infarction and/or treatable or untreatable angina pectoris not responding to treatment) within the past 12 months No uncontrolled, high BP (≥ 150/100 mm Hg) despite optimal medical therapy No current pulmonary disease No active or uncontrolled infections, serious illnesses, malabsorption syndrome, or medical conditions, including patients with a history of chronic alcohol abuse, hepatitis, HIV, and/or cirrhosis No malignancies within the past 5 years except renal cell carcinoma, basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, resected incidental prostate cancer staged pT2 with Gleason Score ≤ 6 and postoperative PSA < 0.5 ng/mL, or patients with any history of malignancies who are disease-free for more than 5 years No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule PRIOR CONCURRENT THERAPY: Prior local radiotherapy for bone lesions allowed No prior systemic therapy for metastatic RCC No prior partial or total nephrectomy No concurrent systemic corticosteroid and/or other immunosuppressive systemic therapies No concurrent radiotherapy, except palliative radiotherapy No concurrent participation in another clinical trial testing treatments for any disease including renal cell carcinoma No other concurrent investigational or systemic therapy for metastatic RCC

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Immediate nephrectomy<br>Surgery followed by Sunitinib | Genetic: gene expression analysis<br> <br> Other: biologic sample preservation procedure<br> <br> Other: laboratory biomarker analysis<br> <br> Procedure: therapeutic conventional surgery<br> <br> |
| Experimental: Deferred nephrectomy<br>Sunitinib (3 cycles) followed by surgery followed by Sunitinib | Procedure: timing of surgery<br> <br> Genetic: gene expression analysis<br> <br> Other: biologic sample preservation procedure<br> <br> Other: laboratory biomarker analysis<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall progression-free survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 
| Morbidity |  |  | 
| Overall response to treatment in the deferred nephrectomy arm including the proportion of patients who become unresectable |  |  | 
| Effect of nephrectomy on early progression in both arms |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clear cell renal cell carcinoma, stage IV renal cell cancer