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

View this study on Beta.ClinicalTrials.gov

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

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Dose Dense MVAC
Arm/Group Description	Dose-dense methotrexate, vinblastin...
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.

Baseline Characteristics

Arm/Group Title		Dose Dense MVAC
Arm/Group Description		Methotrexate: intravenously 30mg/m2...
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
Baseline Analysis Population Description		[Not Specified]
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
United States		39

Outcome Measures

1.Primary Outcome


Title	Number of Patients Achieving Pathologic Response
Description	Pathological response is defined as down-staging to </=pT1, N0 afte...
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)

Outcome Measure Data

Analysis Population Description

Analysis population consists of all enrolled patients.


Arm/Group Title	Dose Dense MVAC
Arm/Group Description:	Methotrexate: intravenously 30mg/m2...
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)

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
Description	Febrile neutropenia defined per CTCAEv3 as Grade 3 or higher and treat...
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)

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Dose Dense MVAC
Arm/Group Description:	Methotrexate: intravenously 30mg/m2...
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
Description	Surgery-related toxicity defined per CTCAEv3 as Grade 2 or higher and ...
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

Outcome Measure Data

Analysis Population Description

Number of patients who underwent cystectomy.


Arm/Group Title	Dose Dense MVAC
Arm/Group Description:	Methotrexate: intravenously 30mg/m2...
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)

Adverse Events

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
Arm/Group Description	Methotrexate: intravenously 30mg/m2...
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	--/--
Serious Adverse Events 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)
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)

Limitations and Caveats

[Not Specified]

More Information

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Choueiri TK, Jacobus S, Bellmunt J, Qu A, Appleman LJ, Tretter C, Bubley GJ, Stack EC, Signoretti S, Walsh M, Steele G, Hirsch M, Sweeney CJ, Taplin ME, Kibel AS, Krajewski KM, Kantoff PW, Ross RW, Rosenberg JE. Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with pegfilgrastim support in muscle-invasive urothelial cancer: pathologic, radiologic, and biomarker correlates. J Clin Oncol. 2014 Jun 20;32(18):1889-94. doi: 10.1200/JCO.2013.52.4785. Epub 2014 May 12.

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

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