Sunitinib Malate With or Without Gemcitabine Hydrochloride in Treating Patients With Advanced Kidney Cancer That Cannot Be Removed By Surgery

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 or by blocking blood flow to the tumor. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to stop the growth or tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving sunitinib malate and gemcitabine hydrochloride together is more effective than sunitinib malate alone in treating patients with kidney cancer. PURPOSE: This randomized phase II clinical trial is studying giving sunitinib malate together with or without gemcitabine hydrochloride to see how well they work in treating patients with advanced kidney cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary To evaluate the response rate to sunitinib malate with vs without gemcitabine hydrochloride in patients with advanced renal cell carcinoma with sarcomatoid features. Secondary To evaluate progression-free survival of these patients. To evaluate overall survival of these patients. To describe the toxic effects of both sunitinib malate alone and in combination with gemcitabine hydrochloride in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to risk (good risk [clear cell and < 20% sarcomatoid and performance status (PS) 0] vs intermediate risk [20-50% sarcomatoid and PS 0] vs poor risk [non-clear cell or > 50% sarcomatoid or PS 1 or non-clear cell]). Patients are randomized to 1 of 2 treatment arms. Arm A: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 22, and 29 and oral sunitinib malate once daily on days 1-14 and 22-35. Arm B: Patients receive oral sunitinib malate once daily on days 1-14 and 22-35. In both arms, courses repeat every 42 days for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year. ACTUAL ACCRUAL: A total of 87 patients (47 in arm A and 40 in arm B) were accrued to this study.

Official Title
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A Randomized Phase II Trial of Sunitinib/Gemcitabine or Sunitinib in Advanced Renal Cell Carcinoma With Sarcomatoid Features

Conditions
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Kidney Cancer

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed* renal cell carcinoma of any subtype containing any sarcomatoid features NOTE: *Patients must have a paraffin-embedded tumor specimen from the kidney or metastatic site available for central review and confirmation of tumor histology Measurable advanced disease that is not resectable by surgery Patients with resected or radiated brain metastases or those treated with stereotactic radiation therapy are eligible, provided they have been off steroids for at least 2 weeks More than 2 weeks since prior radiotherapy and recovered Previously irradiated lesions must not be the sole site of disease Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Absolute neutrophil count (ANC) ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9.0 g/dL (transfusions allowed) Serum creatinine clearance ≥ 30 mL/min serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 times upper limit of normal (ULN; ≤ 5 times ULN in the presence of liver metastases) Total bilirubin ≤ 1.5 times ULN Baseline corrected QT interval < 500 msec on EKG Able to swallow pills Negative pregnancy test Fertile patients must use effective contraception before and during study treatment More than 2 weeks since prior and no concurrent ketoconazole, dexamethasone, dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide, or flecainide), haloperidol, risperidone, rifampin, grapefruit, or grapefruit juice Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been disease free for the time period considered appropriate to not interfere with the outcome of this study Exclusion Criteria: Collecting duct or medullary carcinoma Prior systemic therapy for metastatic disease. One prior therapeutic regimen with a non-tyrosine kinase inhibitor, such as an mtor inhibitor is allowed. Patients who were randomized to placebo on an adjuvant study are eligible History of stroke within the past 6 months. Pregnant or nursing Clinically significant cardiovascular disease, defined as one of the following: Uncontrolled hypertension (blood pressure > 150/100 mm Hg at the time of enrollment); patients with hypertension and BP ≤ 150/100 mm Hg on stable antihypertensive regimen are eligible History of myocardial infarction or unstable angina within the past 24 weeks New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris Peripheral vascular disease ≥ grade II Ongoing ventricular cardiac dysrhythmias ≥ grade 2 as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4 History of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation > 3 beats in a row) Ongoing atrial fibrillation Pre-existing thyroid abnormality with thyroid-stimulating hormone that cannot be maintained at less than or within the normal range with medication Serious concurrent illness or active infection that would jeopardize the ability of the patient to receive study treatment Known HIV

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (Sunitinib + Gemcitabine)<br>Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1, 8, 22, and 29 and oral sunitinib malate once daily on days 1-14 and 22-35. Each cycle was 42 days (6 weeks) and was to be repeated for a total of one year. | Drug: Gemcitabine<br>* Given IV<br>* Other names: Gemzar;Drug: Sunitinib<br>* Given PO<br>* Other names: SU011248;|
| Experimental: Arm B (Sunitinib)<br>Patients receive oral sunitinib malate once daily on days 1-14 and 22-35. Each cycle was 42 days (6 weeks) and was to be repeated for a total of one year. | Drug: Sunitinib<br>* Given PO<br>* Other names: SU011248;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With Response | Response is defined as either complete response (CR, disappearance of all lesions) or partial response (PR, at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters, or persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits). | Assessed every 3 months for 2 years and every 6 months for year 3. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival is defined as the time from randomization to progression or death, whichever occurs first. Progression is defined as follows: At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. | Assessed every 3 months for 2 years and every 6 months for year 3. | 
| Overall Survival | Overall survival is defined as the time from randomization to death or date last known alive. | Assessed every 3 months for 2 years and every 6 months for year 3. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent renal cell cancer, stage IV renal cell cancer, clear cell renal cell carcinoma, papillary renal cell carcinoma, clear cell sarcoma of the kidney