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Dose Dense MVAC for Muscle Invasive Bladder Cancer

Primary Purpose

Muscle Invasive Bladder Cancer, High Risk Urothelial Carcinoma of the Upper Urinary Tracts

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
single arm dose dense MVAC
Sponsored by
Fox Chase Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Muscle Invasive Bladder Cancer focused on measuring bladder, cancer, invasive

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Thomas Jefferson University Hospital
  • Fox Chase Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

dose dense MVAC

Arm Description

standard doses of MVAC given every 14 days x 3.

Outcomes

Primary Outcome Measures

Percentage of Participants With Complete Response at Cystectomy or Ureterectomy Following Preoperative Dose Dense MVAC
complete response rate (pT0), as defined by pathologic staging at cystectomy or ureterectomy, following neoadjuvant DD-MVAC chemotherapy.

Secondary Outcome Measures

Toxicity Profile of Dose Dense MVAC Given in the Neoadjuvant Setting.
Defined by number of patients who complete all three cycles of treatment without dose reduction

Full Information

First Posted
December 3, 2009
Last Updated
August 28, 2019
Sponsor
Fox Chase Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT01031420
Brief Title
Dose Dense MVAC for Muscle Invasive Bladder Cancer
Official Title
Phase II Trial of Neoadjuvant Dose Dense MVAC in Muscle Invasive Bladder Cancer and High Risk Urothelial Carcinoma of the Upper Urinary Tract
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
December 7, 2009 (Actual)
Primary Completion Date
July 19, 2013 (Actual)
Study Completion Date
August 7, 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fox Chase Cancer Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscle Invasive Bladder Cancer, High Risk Urothelial Carcinoma of the Upper Urinary Tracts
Keywords
bladder, cancer, invasive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
dose dense MVAC
Arm Type
Experimental
Arm Description
standard doses of MVAC given every 14 days x 3.
Intervention Type
Drug
Intervention Name(s)
single arm dose dense MVAC
Other Intervention Name(s)
methotrexate (MTX) sodium, MTX, Mexate, Mexate-AQ, Foex, Folex, Abitrexate, Rheumatrex, amethopterin, Velban, Velsar, AlkabanAQ, Velbe, vinblastine sulfate, vincaleukoblastine, VLB, doxorubicin, doxorubicin hydrochloride liposomal Doxil,, Rubex, Adria, cis-platinum, cisdiammineddichloroplatinum,, CDDP, Platinol, platinum
Intervention Description
standard doses of methotrexate, vinblastine, adriamycin, and cisplatin given every 14 days.
Primary Outcome Measure Information:
Title
Percentage of Participants With Complete Response at Cystectomy or Ureterectomy Following Preoperative Dose Dense MVAC
Description
complete response rate (pT0), as defined by pathologic staging at cystectomy or ureterectomy, following neoadjuvant DD-MVAC chemotherapy.
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.
Secondary Outcome Measure Information:
Title
Toxicity Profile of Dose Dense MVAC Given in the Neoadjuvant Setting.
Description
Defined by number of patients who complete all three cycles of treatment without dose reduction
Time Frame
Ongoing throughout treatment at each MD visit every 14 days.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elizabeth Plimack, MD
Organizational Affiliation
Fox Chase Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Thomas Jefferson University Hospital
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24821881
Citation
Plimack ER, Hoffman-Censits JH, Viterbo R, Trabulsi EJ, Ross EA, Greenberg RE, Chen DY, Lallas CD, Wong YN, Lin J, Kutikov A, Dotan E, Brennan TA, Palma N, Dulaimi E, Mehrazin R, Boorjian SA, Kelly WK, Uzzo RG, Hudes GR. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle-invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity. J Clin Oncol. 2014 Jun 20;32(18):1895-901. doi: 10.1200/JCO.2013.53.2465. Epub 2014 May 12.
Results Reference
result
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=24821881
Description
Pubmed.gov

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Dose Dense MVAC for Muscle Invasive Bladder Cancer

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