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Neoadjuvant Chemotherapy With Methotrexate, Vinblastine, Adriamycin and Cisplatin (M-VAC) Plus Avastin in Patients With Urothelial Cancer

2014-08-27 03:37:09 | BioPortfolio

Summary

Objectives:

Primary

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

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 the investigators 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.

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.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. Your complete medical history will be recorded. You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, and temperature), height, and weight. Within 6 months of study entry, you will have an echocardiogram or a multiple gated acquisition (MUGA) scan. Within 6 weeks of study entry, you will have a chest x-ray, a computed tomography (CT) scan and/or magnetic resonance imaging (MRI) scan of the abdomen (stomach area) and pelvis to evaluate the status of your disease. Within 3 weeks of study entry, you will have blood (about 2 teaspoons) and a urine collected for routine tests. This routine blood draw will include a pregnancy test for women who are able to have children. To be eligible to take part in this study, the pregnancy test must be negative.You will have a bone scan if you have bone pain or elevated alkaline phosphatase levels in your blood.

You will have a cystoscopy to check the status of the disease. Your doctor will describe this procedure to you in detail. You will sign a separate consent form for this procedure.

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 M. D. Anderson.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Conditions

Bladder Cancer

Intervention

Avastin, Cisplatin, Doxorubicin, Methotrexate, Vinblastine Sulfate

Location

U.T.M.D. Anderson Cancer Center
Houston
Texas
United States
77030

Status

Recruiting

Source

M.D. Anderson Cancer Center

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:37:09-0400

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Medical and Biotech [MESH] Definitions

An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.

Derivatives of chondroitin which have a sulfate moiety esterified to the galactosamine moiety of chondroitin. Chondroitin sulfate A, or chondroitin 4-sulfate, and chondroitin sulfate C, or chondroitin 6-sulfate, have the sulfate esterified in the 4- and 6-positions, respectively. Chondroitin sulfate B (beta heparin; DERMATAN SULFATE) is a misnomer and this compound is not a true chondroitin sulfate.

Tumors or cancer of the URINARY BLADDER.

An enzyme that catalyzes the activation of sulfate ions by ATP to form adenosine-5'-phosphosulfate and pyrophosphate. This reaction constitutes the first enzymatic step in sulfate utilization following the uptake of sulfate. EC 2.7.7.4.

An arylsulfatase that catalyzes the hydrolysis of the 4-sulfate groups of the N-acetyl-D-galactosamine 4-sulfate units of chondroitin sulfate and dermatan sulfate. A deficiency of this enzyme is responsible for the inherited lysosomal disease, Maroteaux-Lamy syndrome (MUCOPOLYSACCHARIDOSIS VI). EC 3.1.6.12.

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