Sunitinib in Treating Patients With Kidney Cancer That Cannot Be Removed by Surgery

Study Overview
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Brief Summary
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RATIONALE: Sunitinib may stop the growth of kidney cancer by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying the side effects and how well sunitinib works in treating patients with kidney cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: To determine the percentage of patients with renal cell carcinoma and unresectable primary tumors who can achieve sufficient tumor response, according to the operating surgeon, to undergo nephrectomy after sunitinib therapy. To evaluate the safety of sunitinib in patients with renal cell carcinoma and unresectable primary tumors, including analysis of the morbidity of surgery after sunitinib therapy To evaluate the objective response rate of patients with renal cell carcinoma and unresectable primary tumors who receive sunitinib therapy. OUTLINE: A single arm phase II study of sunitinib in patients with unresectable renal cell carcinoma (RCC) will be conducted, including patients with and without distant metastases. Patients receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 42 days in the absence of disease progression or unacceptable toxicity. Surgery is performed if and when primary tumor becomes resectable. Patients with residual and/or metastatic disease may resume sunitinib malate within 8 weeks after surgery. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 31 patients will be accrued for this study.

Official Title
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A Phase II Study of Sunitinib Malate in Patients With Renal Cell Carcinoma and Unresectable Primary Tumors

Conditions
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Kidney Cancer

Intervention / Treatment
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* Drug: sunitinib malate
* Procedure: conventional surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed renal cell carcinoma (any histology) based on prior biopsy or biopsy performed and reviewed at Cleveland Clinic Foundation. This can include pathology read as adenocarcinoma consistent with renal origin. Unresectable primary tumor due to any of the following factors or various combinations thereof: Large tumor size (> 15 cm) Bulky lymphadenopathy (> 4 cm or encasement of renal vessels or great vessels) Venous thrombosis (high level/invasive disease requiring inferior vena cava reconstruction or hypothermic circulatory arrest) Proximity to vital structures (e.g., mesenteric vasculature) Any one of these factors may or may not constitute unresectability, but for consideration for this trial, the surgical and medical oncologist must agree that the particular constellation of findings for the patient under consideration would likely entail a low probability (<50%) that the tumor would be resectable (with negative margins) or that the potential morbidity associated with an attempt at surgical resection would not be clinically acceptable. The numerical thresholds noted above are only a guideline and the clinical judgment of the surgeon and medical oncologist will determine unresectability. Patients with history of brain metastases can be enrolled 2 weeks following the completion of gamma knife or whole brain radiotherapy. ECOG performance status (PS) 0-1 or Karnofsky PS >/=70% Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤ 2.5 times upper limit of normal (ULN) Total Serum Bilirubin ≤ 1.5 times ULN Absolute neutrophil count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 8.0 g/dL (transfusion allowed) Serum calcium ≤ 12.0 mg/dL Creatinine ≤ 2.5 mg/dL Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. Exclusion Criteria: The presence of any of the following will exclude a patient from study enrollment: Prior systemic treatment for RCC. Evidence of bleeding diathesis or coagulopathy. Patients with hematuria from the primary renal tumor are eligible provided all other eligibility criteria are met. Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, severe peripheral vascular disease (claudication) or procedure on peripheral vasculature, coronary/peripheral artery bypass graft, New York Heart Association grade II or greater congestive heart failure, cerebrovascular accident or transient ischemic attack, clinically significant bleeding or pulmonary embolism. Hypertension that cannot be controlled by medications to < 160/90 mmHg. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. Pregnancy or breastfeeding. Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sunitinib<br> | Drug: sunitinib malate<br>* Sunitinib will be dosed at 50 mg p.o. daily<br>* Other names: SUNITINIB;Procedure: conventional surgery<br>* nephrectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to Sunitinib Therapy | Defined as a reduction in tumor burden to such an extent that nephrectomy is permitted within 1 year of the start of therapy. No response to sunitinib therapy is defined as a nephrectomy not being permitted within 1 year of the start of therapy or removal from the study for any reason | 1 year from start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Patients With Any Type of Complication or Adverse Event | The safety of sunitinib will be assessed by recording the number of patients with any type of complication or adverse event within 1 year of the start of therapy. | 1 year from start of treatment | 
| Progression Free Survival | Progression free survival is defined as the amount of time (in months) between the start of treatment and documented RECIST defined progression. RECIST progression is defined as at least a 20% increase in the sum of diameters of target lesions, in addition to an absolute increase of at least 5mm. | 1 year from start of treatment | 
| Percent Decrease of Diameter of Primary Tumors | Median percent decrease in size in all primary renal cell carcinoma tumors. Response was unconfirmed by RECIST criteria because patients went to surgery and did not undergo follow-up scans. | 1 year from start of treatment | 
| Number of Tumors Which Decreased in Size | Number of tumors with at least some reduction in longest primary tumor diameter. Response was unconfirmed by RECIST criteria because patients went to surgery and did not undergo follow-up scans. | 1 year from start of treatment | 
| Number of Tumors With 30% Reduction in Size | Number of tumors with at least 30% reduction in longest primary tumor diameter. Response was unconfirmed by RECIST criteria because patients went to surgery and did not undergo follow-up scans. | 1 year from start of treatment | 
| Median Size Reduction Among Tumors With Some Shrinkage | The median size reduction in the largest diameter of the primary RCC tumor among the tumors with at least some shrinkage in diameter | 1 year from start of treatment | 

 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 III renal cell cancer, stage IV renal cell cancer, papillary renal cell carcinoma