Bevacizumab and Aldesleukin in Treating Patients With Metastatic Clear Cell Carcinoma of the Kidney

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Biological therapies, such as aldesleukin, may stimulate the immune system in different ways and stop tumor cells from growing. Giving bevacizumab together with aldesleukin may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with aldesleukin works in treating patients with metastatic clear cell carcinoma of the kidney.

Detailed Description
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OBJECTIVES: Primary To evaluate the effect of the combination of bevacizumab and aldesleukin on progression-free survival of patients with good- or intermediate-risk metastatic clear cell renal cell carcinoma. Secondary To determine the objective response rate in patients receiving this regimen. To determine the time to progression in patients receiving this regimen. To evaluate immunomodulatory effects of this regimen in patients To evaluate the toxicity of this regimen in these patients. OUTLINE: Patients receive bevacizumab IV over 30-90 minutes on days -14, 1, 15, 29, and 42 and aldesleukin subcutaneously on days 1-5, 8-12, 15-19, 22-26, 29-33, and 36-40. Courses repeat every 8 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients achieving complete response after completion of study therapy may receive 1 additional course of therapy. After completion of study therapy, patients are followed periodically.

Official Title
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Phase II Open Label Trial of rIL-2 and Bevacizumab Combination in Patients With Metastatic Clear Cell Renal Carcinoma

Conditions
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Kidney Cancer

Intervention / Treatment
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* Biological: aldesleukin
* Biological: bevacizumab


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed renal cell carcinoma (RCC) of clear cell histology with or without sarcomatoid features Metastatic disease No non-clear cell RCC (i.e., papillary, collecting-duct, or chromophobe) Good- or intermediate-risk category as defined by having ≤ 2 of the following factors: No prior nephrectomy Karnofsky performance status < 80% Hemoglobin < 12 g/dL Corrected calcium > 10.0 mg/dL LDH > 1.5 times upper limit of normal (ULN) Must have undergone a nephrectomy at least 28 days ago Measurable or evaluable disease by RECIST No significant effusions and/or ascites No prior or concurrent brain or CNS metastasis PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy of ≥ 3 months WBC ≥ 3,000/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9.5 g/dL Creatinine ≤ 2.0 mg/dL Total bilirubin ≤ 1.5 mg/dL AST ≤ 5.0 times ULN Alkaline phosphatase ≤ 2.5 times ULN (≤ 10 times ULN with bone metastasis) Calcium ≤ 12 mg/dL Urine protein:creatinine ratio ≤ 1.0 INR ≤ 1.5 (unless receiving warfarin therapy) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No uncontrolled seizure disorder No known HIV positivity No local or systemic infections requiring IV antibiotics within the past 28 days No significant traumatic injury in the past 28 days No serious non-healing wound, ulcer, or acute bone fracture No evidence of bleeding diathesis or coagulopathy No other malignancy except basal cell or squamous cell carcinoma of the skin, carcinoma in-situ of the uterine cervix, or any malignancy treated with curative intent and in complete remission for > 3 years No history of serious systemic or severe cardiovascular disease, including any of the following: Arterial thromboembolic event (including transient ischemic attack) Cerebrovascular accident Unstable angina Myocardial infarction within the past 6 months Uncontrolled hypertension (BP > 160/110 mm Hg on medication) Uncontrolled cardiac arrhythmia Congestive heart failure Angina pectoris NYHA class III-IV cardiovascular disease Peripheral vascular disease ≥ grade II No history of abdominal fistula and/or bowel or gastric perforation within the past 6 months No history of other diseases, metabolic dysfunction, or physical or laboratory examination findings giving reasonable suspicion of a disease or condition that contraindicate the use of investigational drugs, or that might affect the interpretation of study results, or that render patient at high-risk for treatment complications PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior organ allografts No prior systemic therapy for metastatic clear cell renal cell carcinoma At least 4 weeks since prior radiotherapy and recovered Radiotherapy for control of pain from skeletal lesions allowed within the past 28 days More than 12 months since prior adjuvant therapy More than 7 days since prior fine-needle aspirations or core biopsies More than 28 days since prior and no concurrent major surgery requiring general anesthesia or open biopsy No concurrent aspirin, corticosteroids (except at replacement doses), barbiturates, or other investigational agents

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab and Aldesleukin<br> | Biological: aldesleukin<br>* SQ Aldesleukin (Days 1-5) Monday through Friday for six weeks followed by a two-week break.<br>* Other names: Chiron;Biological: bevacizumab<br>* Bevacizumab will be administered on day -14, then on day 1 and every 2 weeks thereafter (days 1, 15, 29, and 42) in a continuous manner.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression free survival is defined as the time between registration and progression of disease as defined by the RECIST criteria where there is a 20% increase in the diameter of the tumor and at least a 5mm absolute increase in diameter. | From baseline (day -14) to disease progression (reported at 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (Complete and Partial Response) | Objective response rate to be assigned a status of PR or CR per RECIST criteria, with Complete Response (CR) referring to the disappearance of all target lesions, Partial Response (PR) referring to at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met. | 4 weeks after end of treatment | 
| Percentage of Patients With Constitutional Adverse Events | Toxicity Criteria: The NCI graded common clinical toxicity scale (NCI Version 2.0) will be employed to grade observed toxicity of fatigue and fever/chills | From start of treatment to 30 days after treatment | 
| Percentage of Patients With Neutropenia | Toxicity Criteria: The NCI graded common clinical toxicity scale (NCI Version 2.0) will be employed to grade observed toxicity of neutropenia | From start of treatment to 30 days after 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, recurrent renal cell cancer, stage IV renal cell cancer