Clinical trial NCT00113217
Conditions: Renal Cell Carcinoma Kidney Cancer
Keywords: Renal Cell Carcinoma Kidney Cancer Bevacizumab Avastin RCC
Sponsor: M.D. Anderson Cancer Center
Start date: 2005-02-01; Completion date: 2012-08-01
Enrollment: 52 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of this clinical research study is to learn if bevacizumab (Avastin®) can control metastatic renal cell carcinoma (RCC). The safety of the treatment will also be studied.

Objectives:

Primary:

1. To assess the efficacy of neoadjuvant therapy of bevacizumab by evaluating time to progression.
2. Toxicities of therapy with bevacizumab in RCC.

Secondary:

Clinical:

1. Response rate
2. Duration of response
3. Overall Survival

Preclinical:

1. Serum and plasma levels of matrix metalloproteinase 9 (MMP-9) and MMP-2, Interleukin 6 (IL-6), vascular endothelial growth factor (VEGF), and Basic Fibroblast Growth Factor (bFGF) pre- and post- therapy (optional studies).
2. Tissue expression of Phospho-epidermal growth factor receptor (EGFR), VEGF, vessel count CD31/34, AKT and Phospho-AKT, mitogen-activated protein kinase (MAPK), transforming growth factor-alpha (TGF-alpha), phospho-STAT3 and TUNEL post therapy (optional studies).
3. complementary DNA (cDNA) microarray analysis of tissue post-therapy (optional studies).
4. Tissue expression of tumor infiltrating lymphocytes and tumor antigens
5. Pathological response rate in primary tumor.
6. To evaluate the Single Nucleotide Polymorphisms (SNP) patterns in nephrectomy specimens from patients participating in the study.

Detailed description:
Bevacizumab is a drug that binds to and inhibits VEGF, a blood-vessel stimulating agent with unusually high levels in kidney cancer. This drug may decrease the growth of kidney cancer.

Every two week study cycle, you will receive a dose of bevacizumab intravenously (through a needle in your vein). The first bevacizumab dose will be given over 90 minutes as a continuous IV infusion. If the first dose is tolerated without any side effects related to the intravenous (IV) infusion, the second dose may be delivered over 60 minutes. If the 60 minute infusion is tolerated, all doses of bevacizumab after that may be given over 30 minutes. If you experience infusion-related side effects with the 60 minute infusion, all doses after that will be given over 90 minutes. If you experience infusion-related side effects with the 30 minute infusion, all doses after that will be given over 60 minutes. Other drugs, including Tylenol and Benadryl, may be given before, during, and after the therapy to help prevent or ease side effects. These drugs may be given either by mouth or through an IV line.

During treatment, blood samples (about 1 1/2 tablespoons) will be taken once per 2 week cycle. Urine samples will be taken at the beginning of each cycle. At around 56 days into treatment, tumors will be measured using X-rays or other scans.

Treatment will be stopped after 56 days of therapy. In this first phase, you will receive 4 doses of bevacizumab.

If the cancer is stable or shrinks while on bevacizumab for the first 56 days, and you tolerated the treatment well, you will undergo surgery to remove your kidney tumor. Surgery will be scheduled at least 4 weeks after your last dose of bevacizumab. Approximately 4 weeks after surgery, you will undergo repeat CT scans. If your cancer is stable or continuing to shrink, you will restart treatment with bevacizumab. You will continue to have tumor measurements by scans around every 56 days (8 weeks) while receiving bevacizumab, if your initial scans showed evidence of tumor presence. However, If your tumor grew substantially during the operative period, i.e. between the first set of scans on or around day 56 and the scans performed after surgery, you will be taken off the study, and other treatments will be offered to you.

If the cancer grew while on bevacizumab for the first 56 days, you will undergo surgery to remove your kidney tumor. Surgery will be scheduled at least 4 weeks after your last dose of Bevacizumab. After surgery, you will not continue on bevacizumab. Once you recover from surgery, your doctor may recommend a different drug therapy to treat your cancer.

In some circumstances, after the first 56 days of therapy with bevacizumab, your doctors may decide that it is not possible or helpful for your kidney to be removed because of progression of your cancer rendering such an operation either not feasible or inappropriate for your care. In that case, your doctors may recommend a different drug therapy for your cancer, and you will not continue on bevacizumab.

You may be taken off study if your disease progresses or intolerable side effects occur.

If you are taken off study, you will have repeat scans, a physical examination, blood testing (about 2 tablespoons), urine testing, and an ECG. If you have elevated blood pressure or excess protein in your urine, you will be asked to come back every 2 months for repeat blood pressure testing and urine testing until these levels fall to a normal range, for up to one year.

This is an investigational study. Avastin is commercially available and approved by the FDA for metastatic colorectal cancer and small cell lung cancer. The drug is experimental and authorized for research purposes only in renal cell carcinoma. Up to 50 participants will take part in this study. All will be enrolled at The University of Texas (UT) MD Anderson Cancer Center.

Arms: arm 1: 10 mg/kg intravenous (IV) Day 1 of 14-day cycle.
Interventions: intervention 1: Bevacizumab
Intervention descriptions: intervention 1: 10 mg/kg IV on day 1 of each 14-day cycle.

Protocol documents: