Dose Dense MVAC for Muscle Invasive Bladder Cancer

August 28, 2019 updated by: Fox Chase Cancer Center

Phase II Trial of Neoadjuvant Dose Dense MVAC in Muscle Invasive Bladder Cancer and High Risk Urothelial Carcinoma of the Upper Urinary Tract

Standard treatment for early stage bladder cancer is chemotherapy with methotrexate (M), vinblastine (V), adriamycin (A), and cisplatin (C) followed by surgical removal of any remaining cancer and the bladder with the intent of cure. The M V chemotherapy is usually given every 14 days with the AC given along each 28 days. This study looks at giving the same drugs at the same doses closer together, all drugs every 14 days, with the support of growth factor medication to promote growth of the white blood cells and platelets and allow chemotherapy to be finished sooner and surgery to be done sooner.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Primary Objective To assess the rate of complete response (pT0) at cystectomy or ureterectomy following preoperative dose dense MVAC (DD-MVAC) in patients with muscle invasive urothelial carcinoma of the bladder or high grade upper tract urothelial carcinoma.

Secondary Objectives To assess the toxicity profile of DD-MVAC when given in the neoadjuvant setting: To define the number of patients who complete all three cycles of treatment without dose reduction, and to compare incidence of toxicity to the historical standard described by Grossman et al. To assess the 5 year overall and relapse free survival in patients who receive neoadjuvant DD-MVAC. To compare complete response rates between the following subgroups of study patients: Among bladder patients: Clinical N0 versus N1 (Appendix B) Among bladder patients: T2 stage without high risk features versus T2 with high risk features plus those with > T2 stage.

Three 14 day cycles of:

Methotrexate 30 mg/m2 IV push or infusion over 2-3 minutes. Day 1

Vinblastine 3 mg/m2 Slow IV push or infusion over Day 1

Doxorubicin 30 mg/m2 Slow IV push or infusion over 15 minutes Day 1

Cisplatin 70 mg/m2 IV infusion over 4 hours Note: May divide dose over two sequential days (35 mg/m2/d x 2 days) if creatinine clearance 50-59 mL/min Day 1* (or divided over Day 1 and Day 2)

Pegfilgrastim 6 mg subcutaneous (SQ) 24-48 hours after completion of chemotherapy.

Followed in 4-8 weeks by radical cystectomy/ureterectomy.

Study Type

Interventional

Enrollment (Actual)

54

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • histologically confirmed urothelial carcinoma of bladder, ureter, or renal pelvis. T2-T4 and muscle invasion must be established by TURBT. Upper tract must be high grade. N0-N1 are eligible.

  • candidate for radical cystectomy, nephroureterectomy, or segmental ureterectomy with goal of cure.

    ->/= 18 years old

  • ECOG performance status 0-1.
  • Adequate marrow and organ function.
  • May enter on therapeutic anticoagulation if it can be safely held during perioperative period.
  • No women of childbearing potential, pregnant or breastfeeding.
  • LVEF >/= 50 %
  • Patients with history of other non-urothelial malignancies may enroll if: 1)no evidence of distant disease w/in last year. 2)No anticancer treatment for >/= 1 year other than adjuvant treatment or treatment for secondary prevention. 3) Less than 360 mg/m2 lifetime dose of adriamycin.
  • ability to understand and willingness to sign written informed consent and HIPAA.

Exclusion Criteria:

  • Intravesicular therapy w/in 4 weeks of study entry or those who have not recovered from adverse effects of such agents administered more than 4 weeks earlier.
  • Patients may not be receiving any investigational agents within 4 weeks of study entry.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to Methotrexate, Vinblastine, Adriamycin or Cisplatin or other agents used in the study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study due to the potential for teratogenic or abortifacient effects of cytotoxic chemotherapy.

  • Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cytotoxic chemotherapy. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.

    -. Patients who have undergone prior pelvic radiation are excluded due to risk of life threatening myelosuppression.

  • Patients who have received any previous systemic chemotherapy or radiation therapy for urothelial carcinoma or cytotoxic chemotherapy for another malignancy within 1 year of study entry are ineligible.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: dose dense MVAC
standard doses of MVAC given every 14 days x 3.
Drug: single arm dose dense MVAC
standard doses of methotrexate, vinblastine, adriamycin, and cisplatin given every 14 days.
Other Names:
  • CDDP
  • Platinol
  • platinum
  • Abitrexate
  • amethopterin
  • Folex
  • Mexate
  • MTX
  • Mexate-AQ
  • Rheumatrex
  • Rubex
  • Velban
  • Velbe
  • Velsar
  • Adria
  • doxorubicin
  • methotrexate (MTX) sodium
  • Foex
  • AlkabanAQ
  • vinblastine sulfate
  • vincaleukoblastine
  • VLB
  • doxorubicin hydrochloride liposomal Doxil,
  • cis-platinum, cisdiammineddichloroplatinum,

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Complete Response at Cystectomy or Ureterectomy Following Preoperative Dose Dense MVAC
Time Frame: Following completion of the 3rd/final cycle of chemotherapy (about week 9) by CT imaging and at time of surgery for pathologic response.
complete response rate (pT0), as defined by pathologic staging at cystectomy or ureterectomy, following neoadjuvant DD-MVAC chemotherapy.
Following completion of the 3rd/final cycle of chemotherapy (about week 9) by CT imaging and at time of surgery for pathologic response.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity Profile of Dose Dense MVAC Given in the Neoadjuvant Setting.
Time Frame: Ongoing throughout treatment at each MD visit every 14 days.
Defined by number of patients who complete all three cycles of treatment without dose reduction
Ongoing throughout treatment at each MD visit every 14 days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fox Chase Cancer Center

Investigators

  • Principal Investigator: Elizabeth Plimack, MD, Fox Chase Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 7, 2009

Primary Completion (Actual)

July 19, 2013

Study Completion (Actual)

August 7, 2013

Study Registration Dates

First Submitted

December 3, 2009

First Submitted That Met QC Criteria

December 11, 2009

First Posted (Estimate)

December 14, 2009

Study Record Updates

Last Update Posted (Actual)

September 17, 2019

Last Update Submitted That Met QC Criteria

August 28, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FER-GU-026
  • NCI-2010-01910 (Registry Identifier: NCI Clinical Trials Reporting Office)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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