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

This study is ongoing, but not recruiting participants.
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
ClinicalTrials.gov Identifier:
NCT00808639
First received: December 15, 2008
Last updated: June 9, 2014
Last verified: June 2014
  Purpose

The purpose of this research study is to test the effectiveness of neoadjuvant chemotherapy in combination with pegfilgrastim followed by radical surgery in patients with muscle-invasive urothelial carcinoma.


Condition Intervention Phase
Bladder Cancer
Muscle-invasive Bladder Cancer
Drug: Methotrexate
Drug: Doxorubicin
Drug: vinblastine
Drug: cisplatin
Drug: Pegfilgrastim
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Neoadjuvant Dose-Dense MVAC With Pegfilgrastim Support in Subjects With Muscle-Invasive Urothelial Carcinoma

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Number of Patients Achieving Pathologic Response [ Time Frame: After completion of 4 cycles of chemotherapy with pegfilgrastim support (cycle length 2 weeks) ] [ Designated as safety issue: No ]
    Pathological response is defined as down-staging to </=pT1, N0 after chemotherapy with pegfilgrastim support.


Secondary Outcome Measures:
  • Number of Patients Experiencing Febrile Neutropenia [ Time Frame: After completion of 4 cycles of chemotherapy with pegfilgrastim support (cycle length 2 weeks) ] [ Designated as safety issue: Yes ]
    Febrile neutropenia defined per CTCAEv3 as Grade 3 or higher and treatment attribution possibly, probably or definitely-related.

  • Number of Patients Experiencing Surgery-related Toxicity [ Time Frame: Surgery + 30 days ] [ Designated as safety issue: Yes ]
    Surgery-related toxicity defined per CTCAEv3 as Grade 2 or higher and treatment attribution possibly, probably or definitely-related.


Enrollment: 39
Study Start Date: December 2008
Estimated Study Completion Date: June 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Dense MVAC
Chemo therapy with methotrexate, vinblastine, Adriamycin, Cisplatin
Drug: Methotrexate
intravenously 30mg/m2 over 30 minutes
Drug: Doxorubicin
intravenously 30mg/ms over 15 minutes
Drug: vinblastine
intravenously 3mg/m2 over 30 minutes
Drug: cisplatin
intravenously 70mg/m2 in 1 liter NS with 12.5gm Mannitol over 2 hours after vinblastine completion
Drug: Pegfilgrastim
Given subcutaneously 24 hours after last chemotherapy dose

Detailed Description:
  • Participants will be given a study infusion schedule for each treatment cycle. Each treatment cycle lasts three weeks. The infusion of methotrexate will take place on the first day of each cycle. Infusions of vinblastine, doxorubicin and cisplatin will take place on the second day and an injection of pegfilgrastim will be given on the third day.
  • During all treatment cycles participants will have a physical exam and will be asked questions about their general health and any problems they might be having and any medications they may be taking.
  • Following completion of study treatment, but before surgery, participants will have an assessment of their tumor by CT scan of the chest and and MRI of the abdomen and pelvis.
  • Following the participants surgery, we would like to keep track of their medical condition indefinitely, or until this study is officially completed. We would like to do this by calling the participants on the telephone once a year to see how they are doing.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic proof of urothelial cancer. Patients with all histologic subtypes are eligible as long as transitional cell carcinoma is predominant, with the exception of more than a few clusters of small cell carcinoma, which is treated with different chemotherapy and thus are ineligible
  • Patients with primary tumors arising in the bladder or urethra are eligible if they have clinical T2-T4a disease
  • Patients with primary tumors arising in the ureter or renal pelvis are eligible if they have either grade 3 tumors, or radiographic abnormality large enough to be recognized as an abnormal mass by CT/imaging
  • Evaluation by a urologist and be deemed to be acceptable surgical candidates within 3 months of registration
  • Adequate physiologic reserves as outlined in the protocol
  • Clinical or pathologic N1 lymph node involvement (involvement of a single lymph node < 2cm in greatest dimension) are eligible. Patients with N2-3 or M1 disease are ineligible
  • Determination of LV function with an EF > 50%
  • Women of child-bearing potential must have a negative pregnancy test
  • Patients of child-bearing or father-bearing potential must agree to use an acceptable form of birth control while on the study
  • Patients with prior malignancy are eligible provided that the expected outcome from the prior cancer is such that this will not interfere in the delivery of this therapy, or the assessment of response in the cystectomy specimen
  • 18 years of age or older

Exclusion Criteria:

  • Current, recent (within 3 weeks), or planned participation with other experimental anti-cancer medications as part of clinical trials
  • Prior treatment with doxorubicin
  • Prior systemic cytoreductive chemotherapy for bladder cancer
  • Blood pressure of > 160/100 mmHg. Patients whose blood pressure can be controlled with oral medication are eligible
  • 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
  • Evidence of bleeding diathesis or coagulopathy
  • Known history of central nervous system or brain metastases
  • Major surgical procedure, significant traumatic injury within 21 days prior to Day 1, or anticipation of need for major surgical procedure during the course of the study
  • Lactating women
  • Patients who are not candidates for surgery, or unwilling to undergo surgery
  • Patients with significant fluid collection
  • Known hypersensitivity to any component of cisplatin, methotrexate, vinblastine, doxorubicin or pegfilgrastim
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00808639

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Lahey Clinic
Burlington, Massachusetts, United States, 01805
United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Dana-Farber Cancer Institute
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Amgen
Investigators
Principal Investigator: Toni Choueiri, MD Dana-Farber Cancer Institute
  More Information

No publications provided by Dana-Farber Cancer Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Toni Choueiri, MD, Assistant Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00808639     History of Changes
Other Study ID Numbers: 08-208
Study First Received: December 15, 2008
Results First Received: January 14, 2014
Last Updated: June 9, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
pegfilgrastim
MVAC

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma
Carcinoma, Transitional Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liposomal doxorubicin
Cisplatin
Doxorubicin
Methotrexate
Vinblastine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on August 26, 2014