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

NCT00506155 | Completed Phase 2 Results

• 1 other identifier: 2006-0620
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Bladder Cancer

Keywords

Bladder Cancer; Urothelial Cancer; Avastin; Bevacizumab; Cisplatin; Doxorubicin; Methotrexate; Vinblastine; M-VAC

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Response Defined as the Absence of Residual Muscle Invasive Cancer in Resected Specimen

  Number of participants out of total with a response defined as "downstaging" to \<= pT1N0 in the resected specimen. A binary variable was defined for downstaging (pathologic stage below initial clinical stage and below pT1N1N0M0); staging using American Joint Committee on Cancer (AJCC) TNM system of "TNM"; T describes size tumor \& cancer spread into nearby tissue; N describes spread to nearby lymph nodes; \& M describes metastasis (spread to other parts of body). Numbers after T (such as T1, T2, T3, and T4) describe tumor size and/or amount of spread into nearby structures, higher the T number, the larger the tumor and/or more it has grown into nearby tissues. Responses of lesser magnitude scored as treatment failure. Response Evaluation Criteria In Solid Tumors (RECIST) criteria do not apply for this cohort of neoadjuvant participants since this study does not require measurable disease by traditional assessment.

  Following 20 weeks of chemotherapy

Secondary Outcomes (1)

• 5-year Overall Survival (OS)

  5 years

Study Arms (1)

Neoadjuvant Chemotherapy with M-VAC + Avastin

EXPERIMENTAL

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.

Drug: Avastin; Drug: Cisplatin; Drug: Doxorubicin; Drug: Methotrexate; Drug: Vinblastine Sulfate

Interventions

Avastin DRUG

10 mg/kg by vein over 90 minutes

Also known as: Bevacizumab, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

Neoadjuvant Chemotherapy with M-VAC + Avastin

Cisplatin DRUG

70 mg/m\^2 by vein over 4 hours

Also known as: Platinol-AQ, Platinol, CDDP

Neoadjuvant Chemotherapy with M-VAC + Avastin

Doxorubicin DRUG

30 mg/m\^2 by vein over 15 minutes

Also known as: Adriamycin, Rubex

Neoadjuvant Chemotherapy with M-VAC + Avastin

Methotrexate DRUG

30 mg/m\^2 by vein over 30 minutes

Neoadjuvant Chemotherapy with M-VAC + Avastin

Vinblastine Sulfate DRUG

3 mg/m\^2 by vein over 30 minutes

Neoadjuvant Chemotherapy with M-VAC + Avastin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologic proof of urothelial cancer. Patients with all histologic subtypes are eligible as long as transitional cell carcinoma predominant, with 2 exceptions:
• More than a few clusters of small cell carcinoma are treated with different chemotherapy and are ineligible for this study
• Patients with micropapillary tumor will be allowed irrespective of the extent of transitional cell carcinoma. A transitional cell component is not required in the setting of pure or extensive micropapillary tumors. Note that minor histologic components are acceptable.
• Patients with primary tumors arising in the bladder or urethra are eligible if they demonstrate any of the following features:
• A 3-dimensional mass on examination under anesthesia (EUA); ie: cT3b disease
• Direct invasion of prostatic stroma or the vaginal wall: ie:cT4a disease
• Lymphovascular invasion on the specimen with \>/= cT1 disease
• Hydronephrosis present on CT scan or on renal ultrasound
• Tumor involving bladder diverticulum.
• Patients with more than a few areas of micropapillary histology are eligible, even if they do not meet the anatomic criteria for locally advanced disease enumerated above. Patients with micropapillary histology will be analyzed as a separate cohort.
• Patients with primary tumors arising in the ureter or renal pelvis are eligible they have either grade 3 tumor, or a radiographic abnormality large enough to recognize as an abnormal mass by CT or MRI imaging. These patients may also be analyzed separately, since we do not have benchmark data for upper tract disease.
• Patients must have an evaluation in the department of urology, and be deemed an acceptable surgical candidate.
• Patients must have adequate physiologic reserves as by:
• Zubrod performance status (PS) of \</= 1; or 2 if of recent onset and due entirely to the cancer and not due to comorbidity (especially if the compromised performance status is related to uncontrolled pain which is expected to be rapidly reversible when therapy starts)
• Normal WBC, ANC \>/= 1,800, and platelet count \>/= 150,000. Supranormal values judged to be of benign or inconsequential etiology are acceptable

You may not qualify if:

• Patients must not have current, recent (within 3 weeks), or planned participation with other experimental medication clinical trials.
• Prior systemic cytoreductive chemotherapy for bladder cancer. Please note, that prior intra-vesical therapy is allowed.
• Blood pressure of \> 140/90 mmHg. Patients whose blood pressure is controlled with oral medication are eligible, as long as the blood pressure is \</= 140/90 mmHg.
• Any prior history of hypertensive crisis or hypertensive encephalopathy.
• New York Heart Association (NYHA) Grade II or greater congestive heart failure.
• History of myocardial infarction or unstable angina within 6 months prior to study enrollment.
• History of stroke or transient ischemic attack within 6 months prior to study enrollment.
• Clinically significant peripheral vascular disease (e.g., aortic aneurysm, aortic dissection).
• Symptomatic peripheral vascular disease.
• Evidence of bleeding diathesis or coagulopathy.
• Known history of central nervous system or brain metastases.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study. For the purpose of this study, Cystoscopy and ureteroscopy is not included as a major surgical procedure.
• Lactating women.
• Proteinuria at screening as demonstrated by either:
• Urine protein:creatinine (UPC) ratio \>/= 1.0 at screening OR

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 26343003 RESULT

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

Bevacizumab; Cisplatin; Doxorubicin; Methotrexate; Vinblastine

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Results Point of Contact

• Title: Arlene Siefker-Radtke, MD/Associate Professor, Genitourinary Medical Oncology
• Organization: University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

Study Officials

• Arlene Siefker-Radtke, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2007
• First Posted: July 25, 2007
• Study Start: June 1, 2007
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: March 31, 2016
• Results First Posted: March 31, 2016

Record last verified: 2016-03

Locations

US (1)