Clinical trial NCT00506155
Conditions: Bladder Cancer
Keywords: Bladder Cancer Urothelial Cancer Avastin Bevacizumab Cisplatin Doxorubicin Methotrexate Vinblastine M-VAC
Sponsor: M.D. Anderson Cancer Center
Start date: 2007-06-01; Completion date: 2014-08-01
Enrollment: 60 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of this clinical research study is to learn how well bladder cancer responds to a combination treatment with Avastin and M-VAC (methotrexate, doxorubicin, vinblastine, and cisplatin) before surgery to remove the tumor.

Primary Objective:

To estimate the response of patients with locally advanced urothelial cancer treated with neoadjuvant chemotherapy with a combination of Dose Dense Methotrexate, Vinblastine, Adriamycin, and Cisplatin (DD-M-VAC) plus Avastin followed by radical surgery with curative intent. In this context, response will be defined as the absence of residual muscle invasive cancer in the resected specimen (\<= pT1, N0.)

Secondary Objective:

To estimate the 4-year disease-free survival of patients with locally advanced urothelial cancer treated with neoadjuvant chemotherapy with DD-M-VAC plus Avastin followed by radical surgery with curative intent.

Document perioperative morbidity and mortality in this cohort, with reference to well-established historical standards.

Determine the effects of VEGF inhibition on angiogenesis and angiogenesis-related gene expression utilizing fluorescent tissue staining techniques that we have developed in the laboratory (such as two-color TUNEL, phospho-receptor, and microvessel density).

Interrogate downstream receptor signaling pathways to provide insight into the development of chemotherapy resistance, and hence hypothesis for its prevention.

Detailed description:
Avastin is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels. Methotrexate, vinblastine, and doxorubicin are designed to disrupt the growth of cancer cells, which causes cancer cells to start to die. Cisplatin has an atom at its center that contains platinum. The platinum is designed to poison the cancer cells, which may cause them to eventually die.

If you are found to be eligible to take part in this study, you will be treated with the combination of Avastin, methotrexate, vinblastine, doxorubicin, and cisplatin. The study drugs and saline will be given through a needle in your vein. Avastin will be given over 90 minutes. Methotrexate will be given over 30 minutes. Vinblastine will be given over 30 minutes. Doxorubicin will be given over 15 minutes. Cisplatin will be given over 4 hours. You will also receive saline for hydration after you have completed the infusion of cisplatin. This will take up to 20 hours. If you have a catheter in place, the chemotherapy drugs as well as the saline will be given through the catheter. You will receive the study drugs 1 time every 2 weeks. Every 2 weeks is called a study "cycle".

On Day 1 of each cycle, you will have a physical exam, including measurement of your vital signs, height, and weight. You will be asked about any side effects you have experienced since your last visit. Blood (about 2 teaspoons) and urine will be collected for routine tests.

After 3 cycles of therapy, you will have a bone scan if your screening test showed signs of bone disease. You will also have a repeat cystoscopy. These tests will be done to check the status of the disease.

You will receive a total of 4 cycles of chemotherapy. At least 6 weeks after the last dose of Avastin, you will have a cystectomy (removal of your tumor). Your doctor will explain this procedure to you in detail. You will sign a separate consent form for this procedure.

After surgery, if you do not have disease in your lymph nodes or other sites, you will be taken off-study.

After surgery, if you still have disease in your lymph nodes or other sites, you will be eligible to continue treatment with Avastin. Therapy can be restarted no sooner than 28 days after your surgery. You will receive Avastin every 2 or 3 weeks through a needle in your vein. Every 2 or 3 weeks will be considered a study cycle.

Before each cycle of treatment, blood (about 1 teaspoon) will be drawn for routine tests. Urine will be collected every cycle for routine testing. Every 3 months you will have a CT scan or MRI to check the status of the disease.

You may continue to receive the study drug for up to 18 months of therapy. You will be taken off study in the disease gets worse or intolerable side effects occur.

Once you are off-study, you will have long term follow-up visits every 3-6 months for the first 30 months and then every year after that. These visits will continue for up to 4 years, or longer if your doctor thinks it is necessary. At these visits, you will have a CT or MRI scan of your abdomen and pelvis and a chest x-ray. Blood (about 1 teaspoons) will be drawn for routine testing.

This is an investigational study. Avastin is not FDA approved or commercially available for this indication. Its use in this study is considered to be investigational. Methotrexate, doxorubicin, vinblastine, and cisplatin are all FDA approved and commercially available. Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.

Arms: arm 1: Avastin 10 mg/kg by vein over 90 minutes. Cisplatin 70 mg/m\^2 by vein over 4 hours. Doxorubicin 30 mg/m\^2 by vein over 15 minutes. Methotrexate 30 mg/m\^2 by vein over 30 minutes. Vinblastine Sulfate 3 mg/m\^2 by vein over 30 minutes.
Interventions: intervention 1: Avastin intervention 2: Cisplatin intervention 3: Doxorubicin intervention 4: Methotrexate intervention 5: Vinblastine Sulfate
Intervention descriptions: intervention 1: 10 mg/kg by vein over 90 minutes intervention 2: 70 mg/m\^2 by vein over 4 hours intervention 3: 30 mg/m\^2 by vein over 15 minutes intervention 4: 30 mg/m\^2 by vein over 30 minutes intervention 5: 3 mg/m\^2 by vein over 30 minutes

Protocol documents: