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

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ClinicalTrials.gov Identifier: NCT00506155
Recruitment Status : Completed
First Posted : July 25, 2007
Results First Posted : March 31, 2016
Last Update Posted : March 31, 2016
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Bladder Cancer
Interventions Drug: Avastin
Drug: Cisplatin
Drug: Doxorubicin
Drug: Methotrexate
Drug: Vinblastine Sulfate
Enrollment 60
Recruitment Details Recruitment Period: June 1, 2007 to December 13, 2010. All recruitment done at The University of Texas (UT) MD Anderson Cancer.
Pre-assignment Details  
Arm/Group Title Neoadjuvant Chemotherapy With M-VAC + Avastin
Hide Arm/Group Description Avastin 10 mg/kg intravenous (IV) over 90 minutes. Cisplatin 70 mg/m^2 IV over 4 hours. Doxorubicin 30 mg/m^2 IV over 15 minutes. Methotrexate 30 mg/m^2 IV over 30 minutes. Vinblastine Sulfate 3 mg/m^2 IV over 30 minutes.
Period Title: Overall Study
Started 60
Completed 60
Not Completed 0
Arm/Group Title Neoadjuvant Chemotherapy With M-VAC + Avastin
Hide Arm/Group Description Avastin 10 mg/kg intravenous (IV) over 90 minutes. Cisplatin 70 mg/m^2 IV over 4 hours. Doxorubicin 30 mg/m^2 IV over 15 minutes. Methotrexate 30 mg/m^2 IV over 30 minutes. Vinblastine Sulfate 3 mg/m^2 IV over 30 minutes.
Overall Number of Baseline Participants 60
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 60 participants
64
(42 to 79.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants
Female
20
  33.3%
Male
40
  66.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 60 participants
60
Histology of Urothelial Cancer   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 60 participants
Transitional cell carcinoma (TCC) 48
Mixed 12
Mixed, Micropapillary 8
[1]
Measure Description: Histological variants of urothelial tumors classified according to World Health Organization (WHO)/International Society of Urologic Pathologists (ISUP) 2004 guidelines; analysis by histologic types identified as TCC or divergent histologic differentiation (mixed histologic features).
Primary Site   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 60 participants
Renal Pelvis/Ureter 16
Bladder/Urethra 44
[1]
Measure Description: Primary cancer site is location cancer starts in body. All participants with upper tract disease had high-grade disease and were N0M0. Since resection to the muscularis is not possible owing to the inherent risk of perforation in upper tract disease, cancer stage is not available in these participants.
Clinical Stage   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 60 participants
T1N0M0 4
T2N0M0 13
T3-4a N0M0 27
[1]
Measure Description: Clinical cancer stage based on available information obtained before tumor removal surgery using "TNM"; T describes size of tumor and any spread of cancer into nearby tissue; N describes spread of cancer to nearby lymph nodes; & M describes metastasis (spread of cancer 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. All patients with T1 or T2 disease had high risk factor present to be eligible for trial.
High risk feature   [1] 
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 60 participants
Lymphovascular invasion 23
Hydronephrosis 20
Diverticula 1
High-grade upper tract tumor 16
Three-dimensional mass on exam under anesthesia 27
[1]
Measure Description: Low risk or high risk are based upon likelihood of cancer recurrence, including size, number, and appearance of tumor(s), if it recurs, and how deeply it invades into the bladder. A person whose cancer is low risk may be able to have less aggressive treatment and follow up, whereas a person with high risk bladder cancer may require more aggressive treatment and more frequent follow up. Participants may have more than one high-risk feature, so numbers exceed total number of participants.
1.Primary Outcome
Title Percentage of Participants With Response Defined as the Absence of Residual Muscle Invasive Cancer in Resected Specimen
Hide Description 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.
Time Frame Following 20 weeks of chemotherapy
Hide Outcome Measure Data
Hide Analysis Population Description
All 60 participants completed at least 1 cycle of chemotherapy.
Arm/Group Title Neoadjuvant Chemotherapy With M-VAC + Avastin
Hide Arm/Group Description:
Avastin 10 mg/kg intravenous (IV) over 90 minutes. Cisplatin 70 mg/m^2 IV over 4 hours. Doxorubicin 30 mg/m^2 IV over 15 minutes. Methotrexate 30 mg/m^2 IV over 30 minutes. Vinblastine Sulfate 3 mg/m^2 IV over 30 minutes.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: Percentage of Participants
pT0N0 38
pT1N0 53
2.Secondary Outcome
Title 5-year Overall Survival (OS)
Hide Description The overall survival rate stated as a five-year survival rate, which is the percentage of participants in study who are alive five years after the start of treatment.
Time Frame 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Neoadjuvant Chemotherapy With M-VAC + Avastin
Hide Arm/Group Description:
Avastin 10 mg/kg intravenous (IV) over 90 minutes. Cisplatin 70 mg/m^2 IV over 4 hours. Doxorubicin 30 mg/m^2 IV over 15 minutes. Methotrexate 30 mg/m^2 IV over 30 minutes. Vinblastine Sulfate 3 mg/m^2 IV over 30 minutes.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: Percentage of Participants
63
Time Frame Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Neoadjuvant Chemotherapy With M-VAC + Avastin
Hide Arm/Group Description Avastin 10 mg/kg intravenous (IV) over 90 minutes. Cisplatin 70 mg/m^2 IV over 4 hours. Doxorubicin 30 mg/m^2 IV over 15 minutes. Methotrexate 30 mg/m^2 IV over 30 minutes. Vinblastine Sulfate 3 mg/m^2 IV over 30 minutes.
All-Cause Mortality
Neoadjuvant Chemotherapy With M-VAC + Avastin
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Neoadjuvant Chemotherapy With M-VAC + Avastin
Affected / at Risk (%)
Total   6/60 (10.00%) 
Infections and infestations   
Neutropenia/neutropenic fever † 1  6/60 (10.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (2.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Neoadjuvant Chemotherapy With M-VAC + Avastin
Affected / at Risk (%)
Total   33/60 (55.00%) 
Blood and lymphatic system disorders   
Anemia † 1  4/60 (6.67%) 
Cardiac disorders   
Hypertension † 1  4/60 (6.67%) 
Hypotension † 1  1/60 (1.67%) 
Cardiac ischemia † 1  1/60 (1.67%) 
Gastrointestinal disorders   
Nausea/Vomiting † 1  3/60 (5.00%) 
Mucositis † 1  2/60 (3.33%) 
General disorders   
Fatigue † 1  7/60 (11.67%) 
Infections and infestations   
Neutropenia/neutropenic fever † 1  10/60 (16.67%) 
Metabolism and nutrition disorders   
Hyponatremia † 1  1/60 (1.67%) 
Transaminitis † 1  1/60 (1.67%) 
Nervous system disorders   
Syncope † 1  2/60 (3.33%) 
Respiratory, thoracic and mediastinal disorders   
Thrombosis/pulmonary embolism † 1  3/60 (5.00%) 
Skin and subcutaneous tissue disorders   
Thrombocytopenia † 1  2/60 (3.33%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (2.0)
[Not Specified]
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Arlene Siefker-Radtke, MD/Associate Professor, Genitourinary Medical Oncology
Organization: University of Texas (UT) MD Anderson Cancer Center
EMail: CR_Study_Registration@mdanderson.org
Publications of 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-naïve 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.
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00506155    
Other Study ID Numbers: 2006-0620
First Submitted: July 23, 2007
First Posted: July 25, 2007
Results First Submitted: March 1, 2016
Results First Posted: March 31, 2016
Last Update Posted: March 31, 2016