Trial Outcomes & Findings for Neoadjuvant Chemotherapy With Methotrexate, Vinblastine, Adriamycin and Cisplatin (M-VAC) Plus Avastin in Patients With Urothelial Cancer (NCT NCT00506155)

Last Updated: 2016-03-31

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

Following 20 weeks of chemotherapy

Results posted on

2016-03-31

Participant Flow

Recruitment Period: June 1, 2007 to December 13, 2010. All recruitment done at The University of Texas (UT) MD Anderson Cancer.

Participant milestones

Participant milestones
Measure	Neoadjuvant Chemotherapy With M-VAC + Avastin 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 Study STARTED	60
Overall Study COMPLETED	60
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Neoadjuvant Chemotherapy With M-VAC + Avastin n=60 Participants 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.
Age, Continuous	64 years n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants
Region of Enrollment United States	60 participants n=5 Participants
Histology of Urothelial Cancer Transitional cell carcinoma (TCC)	48 participants n=5 Participants
Histology of Urothelial Cancer Mixed	12 participants n=5 Participants
Histology of Urothelial Cancer Mixed, Micropapillary	8 participants n=5 Participants
Primary Site Renal Pelvis/Ureter	16 participants n=5 Participants
Primary Site Bladder/Urethra	44 participants n=5 Participants
Clinical Stage T1N0M0	4 participants n=5 Participants
Clinical Stage T2N0M0	13 participants n=5 Participants
Clinical Stage T3-4a N0M0	27 participants n=5 Participants
High risk feature Lymphovascular invasion	23 participants n=5 Participants
High risk feature Hydronephrosis	20 participants n=5 Participants
High risk feature Diverticula	1 participants n=5 Participants
High risk feature High-grade upper tract tumor	16 participants n=5 Participants
High risk feature Three-dimensional mass on exam under anesthesia	27 participants n=5 Participants

PRIMARY outcome

Timeframe: Following 20 weeks of chemotherapy

Population: All 60 participants completed at least 1 cycle of chemotherapy.

Outcome measures

Outcome measures
Measure	Neoadjuvant Chemotherapy With M-VAC + Avastin n=60 Participants 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.
Percentage of Participants With Response Defined as the Absence of Residual Muscle Invasive Cancer in Resected Specimen pT0N0	38 Percentage of Participants
Percentage of Participants With Response Defined as the Absence of Residual Muscle Invasive Cancer in Resected Specimen pT1N0	53 Percentage of Participants

SECONDARY outcome

Timeframe: 5 years

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.

Outcome measures

Outcome measures
Measure	Neoadjuvant Chemotherapy With M-VAC + Avastin n=60 Participants 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.
5-year Overall Survival (OS)	63 Percentage of Participants

Adverse Events

Neoadjuvant Chemotherapy With M-VAC + Avastin

Serious events: 6 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Neoadjuvant Chemotherapy With M-VAC + Avastin n=60 participants at risk 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.
Infections and infestations Neutropenia/neutropenic fever	10.0% 6/60 • Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.

Other adverse events

Other adverse events
Measure	Neoadjuvant Chemotherapy With M-VAC + Avastin n=60 participants at risk 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.
Infections and infestations Neutropenia/neutropenic fever	16.7% 10/60 • Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.
General disorders Fatigue	11.7% 7/60 • Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.
Cardiac disorders Hypertension	6.7% 4/60 • Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.
Blood and lymphatic system disorders Anemia	6.7% 4/60 • Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.
Respiratory, thoracic and mediastinal disorders Thrombosis/pulmonary embolism	5.0% 3/60 • Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.
Gastrointestinal disorders Nausea/Vomiting	5.0% 3/60 • Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.
Gastrointestinal disorders Mucositis	3.3% 2/60 • Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.
Skin and subcutaneous tissue disorders Thrombocytopenia	3.3% 2/60 • Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.
Nervous system disorders Syncope	3.3% 2/60 • Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.
Metabolism and nutrition disorders Hyponatremia	1.7% 1/60 • Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.
Cardiac disorders Hypotension	1.7% 1/60 • Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.
Metabolism and nutrition disorders Transaminitis	1.7% 1/60 • Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.
Cardiac disorders Cardiac ischemia	1.7% 1/60 • Adverse event reporting collected through cystectomy performed at a minimum of 6 weeks from the last dose of Avastin.

Additional Information

Arlene Siefker-Radtke, MD/Associate Professor, Genitourinary Medical Oncology

University of Texas (UT) MD Anderson Cancer Center

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place