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Dose-Dense MVAC With Pegfilgrastim Support in Subjects With Muscle-Invasive Urothelial Carcinoma

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ClinicalTrials.gov Identifier: NCT00808639
Recruitment Status : Completed
First Posted : December 16, 2008
Results First Posted : May 15, 2014
Last Update Posted : October 24, 2016
Sponsor:
Collaborators:
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Amgen
Information provided by (Responsible Party):
Toni Choueiri, MD, Dana-Farber Cancer Institute

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Bladder Cancer
Muscle-invasive Bladder Cancer
Interventions Drug: Methotrexate
Drug: Doxorubicin
Drug: vinblastine
Drug: cisplatin
Drug: Pegfilgrastim
Enrollment 39
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Dose Dense MVAC
Hide Arm/Group Description Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC)
Period Title: Overall Study
Started 39
Completed 38 [1]
Not Completed 1
Reason Not Completed
Disease progression before surgery.             1
[1]
One patient went off treatment due to disease progression before surgery.
Arm/Group Title Dose Dense MVAC
Hide Arm/Group Description

Methotrexate: intravenously 30mg/m2 over 30 minutes

Doxorubicin: intravenously 30mg/ms over 15 minutes

vinblastine: intravenously 3mg/m2 over 30 minutes

cisplatin: intravenously 70mg/m2 in 1 liter NS with 12.5gm Mannitol over 2 hours after vinblastine completion

Pegfilgrastim: Given subcutaneously 24 hours after last chemotherapy dose

Overall Number of Baseline Participants 39
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 39 participants
57
(43 to 76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants
Female
11
  28.2%
Male
28
  71.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
39
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 39 participants
39
1.Primary Outcome
Title Number of Patients Achieving Pathologic Response
Hide Description Pathological response is defined as down-staging to </=pT1, N0 after chemotherapy with pegfilgrastim support.
Time Frame After completion of 4 cycles of chemotherapy with pegfilgrastim support (cycle length 2 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population consists of all enrolled patients.
Arm/Group Title Dose Dense MVAC
Hide Arm/Group Description:

Methotrexate: intravenously 30mg/m2 over 30 minutes

Doxorubicin: intravenously 30mg/ms over 15 minutes

vinblastine: intravenously 3mg/m2 over 30 minutes

cisplatin: intravenously 70mg/m2 in 1 liter NS with 12.5gm Mannitol over 2 hours after vinblastine completion

Pegfilgrastim: Given subcutaneously 24 hours after last chemotherapy dose

Overall Number of Participants Analyzed 39
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: percentage of pathologic responders
49
(35 to 63)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dose Dense MVAC
Comments This study used a Simon's optimal two-stage design. Of 39 eligible patients, if 18 achieved PaR, the treatment would be declared effective. A two-sided 80% CI was estimated considering the two-stage design based on Atkinson and Brown methods.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Pathologic response rate
Estimated Value 49
Confidence Interval (2-Sided) 80%
38 to 61
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Patients Experiencing Febrile Neutropenia
Hide Description Febrile neutropenia defined per CTCAEv3 as Grade 3 or higher and treatment attribution possibly, probably or definitely-related.
Time Frame After completion of 4 cycles of chemotherapy with pegfilgrastim support (cycle length 2 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Dose Dense MVAC
Hide Arm/Group Description:

Methotrexate: intravenously 30mg/m2 over 30 minutes

Doxorubicin: intravenously 30mg/ms over 15 minutes

vinblastine: intravenously 3mg/m2 over 30 minutes

cisplatin: intravenously 70mg/m2 in 1 liter NS with 12.5gm Mannitol over 2 hours after vinblastine completion

Pegfilgrastim: Given subcutaneously 24 hours after last chemotherapy dose

Overall Number of Participants Analyzed 39
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: participants
0
(0 to 0)
3.Secondary Outcome
Title Number of Patients Experiencing Surgery-related Toxicity
Hide Description Surgery-related toxicity defined per CTCAEv3 as Grade 2 or higher and treatment attribution possibly, probably or definitely-related.
Time Frame Surgery + 30 days
Hide Outcome Measure Data
Hide Analysis Population Description
Number of patients who underwent cystectomy.
Arm/Group Title Dose Dense MVAC
Hide Arm/Group Description:

Methotrexate: intravenously 30mg/m2 over 30 minutes

Doxorubicin: intravenously 30mg/ms over 15 minutes

vinblastine: intravenously 3mg/m2 over 30 minutes

cisplatin: intravenously 70mg/m2 in 1 liter NS with 12.5gm Mannitol over 2 hours after vinblastine completion

Pegfilgrastim: Given subcutaneously 24 hours after last chemotherapy dose

Overall Number of Participants Analyzed 38
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: participants
4
(4 to 22)
Time Frame Reported adverse events include events starting on or after day 0 through 30 days post treatment.
Adverse Event Reporting Description Toxicities are reported by toxicity type and maximum grade (consolidates the reports of a given type of toxicity for a patient over time) for attributions possibly, probably and definitely related to treatment only. Patients with reports of multiple toxicities of different types are reported multiple times under the relevant toxicity categories.
 
Arm/Group Title Dose Dense MVAC
Hide Arm/Group Description

Methotrexate: intravenously 30mg/m2 over 30 minutes

Doxorubicin: intravenously 30mg/ms over 15 minutes

vinblastine: intravenously 3mg/m2 over 30 minutes

cisplatin: intravenously 70mg/m2 in 1 liter NS with 12.5gm Mannitol over 2 hours after vinblastine completion

Pegfilgrastim: Given subcutaneously 24 hours after last chemotherapy dose

All-Cause Mortality
Dose Dense MVAC
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Dose Dense MVAC
Affected / at Risk (%)
Total   4/39 (10.26%) 
Gastrointestinal disorders   
Muco/stomatitis by exam, oral cavity  1  1/39 (2.56%) 
Infections and infestations   
Infection w/ gr3-4 neut, urinary tract  1  1/39 (2.56%) 
Metabolism and nutrition disorders   
Hypokalemia  1  1/39 (2.56%) 
Skin and subcutaneous tissue disorders   
Hand-foot reaction  1  1/39 (2.56%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Dose Dense MVAC
Affected / at Risk (%)
Total   32/39 (82.05%) 
Blood and lymphatic system disorders   
Hemoglobin  1  2/39 (5.13%) 
Ear and labyrinth disorders   
Tinnitus  1  1/39 (2.56%) 
Tinnitus  1  3/39 (7.69%) 
Gastrointestinal disorders   
Chelitis  1  1/39 (2.56%) 
Constipation  1  9/39 (23.08%) 
Diarrhea w/o prior colostomy  1  1/39 (2.56%) 
Dysphagia  1  2/39 (5.13%) 
Gastritis  1  1/39 (2.56%) 
Dyspepsia  1  3/39 (7.69%) 
Muco/stomatitis by exam, oral cavity  1  4/39 (10.26%) 
Muco/stomatitis (symptom) oral cavity  1  9/39 (23.08%) 
Nausea  1  15/39 (38.46%) 
Vomiting  1  4/39 (10.26%) 
GI-other  1  1/39 (2.56%) 
General disorders   
Fatigue  1  27/39 (69.23%) 
Edema limb  1  1/39 (2.56%) 
Pain-other  1  1/39 (2.56%) 
Infections and infestations   
Opportunistic infection lymphopenia>=gr1  1  1/39 (2.56%) 
Infection Gr0-2 neut, mucosa  1  1/39 (2.56%) 
Infection Gr0-2 neut, oral cavity  1  1/39 (2.56%) 
Investigations   
Leukocytes  1  1/39 (2.56%) 
Weight loss  1  2/39 (5.13%) 
Coagulation-other  1  1/39 (2.56%) 
ALT, SGPT  1  1/39 (2.56%) 
Metabolism and nutrition disorders   
Anorexia  1  8/39 (20.51%) 
Hypomagnesemia  1  3/39 (7.69%) 
Hypokalemia  1  1/39 (2.56%) 
Musculoskeletal and connective tissue disorders   
Nonneuropathic generalized weakness  1  1/39 (2.56%) 
Musculoskeletal/soft tissue-other  1  1/39 (2.56%) 
Muscle, pain  1  1/39 (2.56%) 
Nervous system disorders   
Taste disturbance  1  7/39 (17.95%) 
Dizziness  1  3/39 (7.69%) 
Neuropathy CN I smell  1  1/39 (2.56%) 
Neuropathy-sensory  1  1/39 (2.56%) 
Head/headache  1  5/39 (12.82%) 
Renal and urinary disorders   
Urinary frequency/urgency  1  1/39 (2.56%) 
Respiratory, thoracic and mediastinal disorders   
Muco/stomatitis (symptom) trachea  1  1/39 (2.56%) 
Nose, hemorrhage  1  3/39 (7.69%) 
Edema, larynx  1  1/39 (2.56%) 
Voice changes/dysarthria  1  1/39 (2.56%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  1/39 (2.56%) 
Photosensitivity  1  1/39 (2.56%) 
Pruritus/itching  1  1/39 (2.56%) 
Hand-foot reaction  1  2/39 (5.13%) 
Vascular disorders   
Phlebitis  1  2/39 (5.13%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
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: Toni Choueiri, MD
Organization: Dana-Farber Cancer Institute
Phone: 617-632-5456
EMail: toni_choueiri@dfci.harvard.edu
Layout table for additonal information
Responsible Party: Toni Choueiri, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00808639    
Other Study ID Numbers: 08-208
First Submitted: December 15, 2008
First Posted: December 16, 2008
Results First Submitted: January 14, 2014
Results First Posted: May 15, 2014
Last Update Posted: October 24, 2016