Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Risk Adapted Treatment for Muscle Invasive Bladder Cancer After Neoadjuvant Accelerated MVAC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02710734
Recruitment Status : Recruiting
First Posted : March 17, 2016
Last Update Posted : November 17, 2017
Sponsor:
Information provided by (Responsible Party):
Fox Chase Cancer Center

Tracking Information
First Submitted Date  ICMJE February 18, 2016
First Posted Date  ICMJE March 17, 2016
Last Update Posted Date November 17, 2017
Actual Study Start Date  ICMJE February 24, 2016
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2017)
Metastasis-free survival (MFS) at 2 years. [ Time Frame: 24 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 11, 2016)
  • Number of subjects completing treatment [ Time Frame: Up to 22 weeks ]
  • Time to recurrence of disease based on RECIST Criteria v 1.1 [ Time Frame: Up to 2 years ]
Change History Complete list of historical versions of study NCT02710734 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2017)
Ability to complete of 3 cycles of neoadjuvant AMVAC and chemoradiation therapy with 5-FU and mitomycin C. [ Time Frame: Up to 37 Weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2016)
Number of subjects experiencing serious adverse events per CTCAE v4.03 [ Time Frame: Up to 22 Weeks ]
Current Other Pre-specified Outcome Measures
 (submitted: August 18, 2017)
  • Rate of urothelial carcinoma recurrence in active surveillance patients [ Time Frame: 60 months ]
  • Overall survival and PFS of the entire cohort [ Time Frame: 60 months ]
  • toxicity during each treatment arm according to NCI CTCAE v 4.01 criteria [ Time Frame: 24 months ]
  • Proportion of patients with ≥cT1 disease after TURBT#2 [ Time Frame: up to 22 weeks ]
  • Proportion of patients requiring a cystectomy, either immediately after TURBT#2 or as salvage after surveillance or CRT [ Time Frame: up to 24 months ]
  • Endoscopic Tumor Quantification System score at each TURBT [ Time Frame: 24 months ]
    At each cystoscopic examination, the location and extent of tumor volume will be visually depicted and graded according to Endoscopic Tumor Quantification System
  • Quality of life with neoadjuvant AMVAC and subsequent risk-adapted treatment [ Time Frame: 60 months ]
    American Urologic Association (AUA) Symptom Index Score, Sexual Health Inventory for Men (SHIM) score or Female Sexual Function Index (FSFI) score
Original Other Pre-specified Outcome Measures
 (submitted: March 11, 2016)
  • Rate absent detectable tumor by urine cytology following neoadjuvant MVAC and following chemoradiation therapy [ Time Frame: Week 14 ]
  • Number of subject who cystectomy for tumor recurrence or unacceptable genitourinary toxicity. [ Time Frame: Up to 2 years ]
  • Quality of Life Questionnaire Measuring AUA scores [ Time Frame: Baseline, Week 8, Week 11, Week 14, Week 22, Every 4 months for 2 years, every 6 months up to year 5 ]
  • Rate absent detectable tumor by targeted cystoscopic biopsies following neoadjuvant MVAC and following chemoradiation therapy [ Time Frame: Week 14 ]
 
Descriptive Information
Brief Title  ICMJE Risk Adapted Treatment for Muscle Invasive Bladder Cancer After Neoadjuvant Accelerated MVAC
Official Title  ICMJE A Phase II Trial of Risk Adapted Treatment for Muscle Invasive Bladder Cancer After Neoadjuvant Accelerated MVAC (RAT-MIBC)
Brief Summary The aim of this study is to evaluate a risk-adapted approach to the treatment of muscle invasive bladder cancer. Each baseline transuretheral resection of bladder tumor (TURBT) sample will be sequenced while proceeding with neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) chemotherapy. Based on the mutational profile and the post AMVAC TURBT findings, patients will be treated with active surveillance (experimental arm), or standard of care intravesicle therapy, chemoradiation or surgery. We hypothesize that this approach will lead to non-inferior metastasis-free survival at 2 years, while preserving the bladder and thus quality-of-life for a proportion of patients.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Urothelial Carcinoma of the Bladder
Intervention  ICMJE
  • Drug: Methotrexate
    Administered Day 1 of each 14 day cycle for 3 cycles
  • Drug: Vinblastine
    Administered Day 1 of each 14 day cycle for 3 cycles
  • Drug: Doxorubicin
    Administered Day 1 of each 14 day cycle for 3 cycles
  • Drug: Cisplatin
    Administered Day 1 of each 14 day cycle for 3 cycles
  • Radiation: Intensity modulated radiation therapy (IMRT)
    2.0 Gy per fraction to the whole bladder plus a margin for a total of 32 fractions (64.0 Gy). Radiation will be administered from Monday to Friday
  • Procedure: Transurethral Resection of Bladder tumor
    Performed at before and after AMVAC and after chemoradiation and intravesicle therapy
  • Drug: 5-FU
    Continuous 24hr Intravenous infusion days 1-5 and 16-20 with radiation treatment
  • Drug: Mitomycin C
    Intravenous on day 1 with radiation treatment
Study Arms  ICMJE
  • Experimental: CRT
    Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then chemoradiation followed by TURBT#3
    Interventions:
    • Drug: Methotrexate
    • Drug: Vinblastine
    • Drug: Doxorubicin
    • Drug: Cisplatin
    • Radiation: Intensity modulated radiation therapy (IMRT)
    • Procedure: Transurethral Resection of Bladder tumor
    • Drug: 5-FU
    • Drug: Mitomycin C
  • Experimental: Surveillance
    Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then active surveillance
    Interventions:
    • Drug: Methotrexate
    • Drug: Vinblastine
    • Drug: Doxorubicin
    • Drug: Cisplatin
    • Procedure: Transurethral Resection of Bladder tumor
  • Experimental: Intravesicle therapy
    Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then intravesicle therapy followed by TURBT#3
    Interventions:
    • Drug: Methotrexate
    • Drug: Vinblastine
    • Drug: Doxorubicin
    • Drug: Cisplatin
    • Procedure: Transurethral Resection of Bladder tumor
  • Experimental: Radical Cystectomy
    Trimodality of Maximal TURBT#1 Followed by AMVAC and TURBT#2 and then cystectomy
    Interventions:
    • Drug: Methotrexate
    • Drug: Vinblastine
    • Drug: Doxorubicin
    • Drug: Cisplatin
    • Procedure: Transurethral Resection of Bladder tumor
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 11, 2016)
38
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2023
Estimated Primary Completion Date April 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female patients ≥18 years.
  • Primary urothelial or predominantly urothelial carcinoma of the bladder.
  • Histologic evidence of muscularis propria invasion.
  • AJCC27 clinical stage T2-T4a .
  • No radiographic evidence of lymph node positivity (N0) or metastatic disease (M0). Clinical lymphadenopathy on staging CT greater than 1.5 cm in short axis must be biopsy proven negative.
  • ECOG performance status 0, 1, or 2.
  • Left ventricular ejection fraction ≥ 50% by MUGA or ECHO within 6 months of study entry.
  • Normal organ and bone marrow function as defined:

Leukocytes ≥ 3,000/mcL Absolute neutrophil count ≥ 1,500/mcL Platelets ≥ 100,000/mcL Total bilirubin ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional ULN Creatinine Creatinine Clearance ≥ 50 mL/min (calculated using the Cockroft-Gault formula or measured with 24 hour urine collection)

Exclusion Criteria:

  • Any component of small cell histology.
  • Prior pelvic radiation therapy or patients who have undergone prior radiation to greater than or equal to 25% of the bone marrow within the past year are excluded due to risk of life threatening myelosuppression
  • Prior systemic chemotherapy; 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.
  • Prior or concurrent malignancy of any other site except for non-melanoma skin cancer, unless disease free interval ≥ 5 years.
  • Patients who have received experimental 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 (defined by current oral or intravenous antibiotic therapy), 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 with hydronephrosis that has not been addressed with an intervention such as placement of a stent.
  • Pregnancy & Women of Childbearing Potential
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Daniel Geynisman, MD 215-214-1515 Daniel.Geynisman@fccc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02710734
Other Study ID Numbers  ICMJE GU-086
15-1071 ( Other Identifier: Fox Chase Cancer Center IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Fox Chase Cancer Center
Study Sponsor  ICMJE Fox Chase Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Fox Chase Cancer Center
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP