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

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.

Timeline

Start

2007-06

Primary completion

2014-08

Completion

2014-08

Publications

• Results McConkey DJ, Choi W, Shen Y, Lee IL, Porten S, Matin SF, Kamat AM, Corn P, Millikan RE, Dinney C, Czerniak B, Siefker-Radtke AO. A Prognostic Gene Expression Signature in the Molecular Classification of Chemotherapy-naive Urothelial Cancer is Predictive of Clinical Outcomes from Neoadjuvant Chemotherapy: A Phase 2 Trial of Dose-dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin with Bevacizumab in Urothelial Cancer. Eur Urol. 2016 May;69(5):855-62. doi: 10.1016/j.eururo.2015.08.034. Epub 2015 Sep 3.

Drugs

Indications