Mitomycin C With Hyperthermia and Intravesical Mitomycin C to Treat Recurrent Bladder Cancer

June 1, 2015 updated by: Mark Dewhirst

Pilot Study of External Hyperthermia and Intravesical Mitomycin-C To Treat Recurrent Bladder Cancer After Resection and Standard Adjuvant Therapy

Hypothesis: In selected patients external hyperthermia will be used in combination with intravesical Mitomycin-C (MMC) to treat recurrent transitional cell carcinoma (TCC) of the bladder after local resection and standard adjuvant therapy and thus prevent or delay recurrence and the need for radical cystectomy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

It is well established that tumor cells are sensitive to heat and when combined with a chemotherapeutic agent, drug uptake and intracellular distribution of drug within malignant cells is improved due to increased cellular permeability. Further, hyperthermia inhibits deoxyribonucleic acid (DNA) repair as a result of increased reaction between DNA and chemotherapy. By heating bladder tissue and accelerating the necessary series of reactions to link agents such as mitomycin C to cell DNA, this effect may be optimized. Depending on the extent of resection (and location, size, and depth of invasion of remaining tumor) after transurethral resection of the bladder tumor(TURBT), recommended adjuvant therapy consists of intravesical chemotherapy. MMC has been studied at doses as high as 80 mg without producing significant or irreversible side effects. The most commonly used dose of mitomycin is 40 mg.2

This pilot study proposes to use Mitomycin C at a dose of 40 mg in conjunction with deep hyperthermia to enhance the effect intravesical chemotherapy as second-line treatment of recurrent TCC (Stage Ta, T1, or Tis) of the bladder after surgical resection and standard adjuvant therapy.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Early Phase 1

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
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center

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

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Non-muscle invasive transitional cell carcinoma (TCC) of the bladder (Ta, T1, Tis) recurrent after initial surgery and at least one round of adjuvant treatment (i.e. 6 weeks of intravesical biological therapy with Bacillus Calmette Guerin (BCG) solution); or
  • An inability to tolerate BCG
  • Age > 18
  • Eastern Cooperative Oncology Group(ECOG) Performance Status 0-2

  • Laboratory tests performed within 14 days of study enrollment:

    • Leukocytes ≥ 3,200, Absolute Neutrophil count ≥ 1,500, Platelets ≥ 100,000
    • Hemoglobin ≥ 9.0 gm/dL, Total bilirubin ≤ institution upper limit of normal *(ULN), Asparate Aminotransferase(AST) and Alanine Aminotransferase(ALT) ≤ 2.5 times ULN, Alkaline phosphatase ≤ 2.5 times ULN
    • Creatinine ≤ 1.5 times ULN
  • Women of child bearing potential must have a negative pregnancy test
  • If post-menopausal - Amenorrhea for ≥ 12 months

Exclusion Criteria:

  • Pregnancy or breastfeeding
  • Muscle invasive disease (T2-T4)
  • Prior radiation to the pelvis
  • Peripheral neuropathy (any grade)
  • Thrombocytopenia, coagulation disorder or an increase in bleeding tendency due to other causes
  • Known bladder fistula
  • Hypersensitive or idiosyncratic reaction to mitomycin-C or its components in the past

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: Hyperthermia system, Mitomycin C
Pilot study single arm study to test the safety, tolerability and clinical benefit of regional hyperthermia and mitomycin-C intravesical chemotherapy to treat non-invasive Transitional Cell carcinoma (TCC) of the bladder that has recurred after standard resection and adjuvant therapy.
Device: Hyperthermia System
Hyperthermia applied to heat the bladder to a temperature of 42 degrees Celsius for 40-60 minutes concurrent with mitomycin Treatment Schedule: 6 Weekly Sessions (Induction) followed by 4 Monthly Sessions (Maintenance) until documented second recurrence
Other Names:
  • BSD 2000 Hyperthermia system
Drug: Mitomycin C
40 mg in 40 ml sterile water instilled into bladder
Other Names:
  • Mutamycin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and Tolerability
Time Frame: During Treatment Phase average 6 weeks
Number of patient treatments stopped due to safety concerns or treatment intolerability. All events below are grade 1/2 toxicity. No grade 3-5 toxicity was observed.
During Treatment Phase average 6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Recurrence Free-survival
Time Frame: Median follow-up 3.18 years
Time to first recurrence of cancer in the bladder.
Median follow-up 3.18 years

Collaborators and Investigators

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

Sponsor

Mark Dewhirst

Investigators

  • Principal Investigator: Zelko Vujaskovic, MD, Duke University
  • Principal Investigator: Brant A Inman, MD, MS, Duke University

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

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

April 1, 2008

Primary Completion (Actual)

February 1, 2011

Study Completion (Actual)

March 1, 2011

Study Registration Dates

First Submitted

May 4, 2008

First Submitted That Met QC Criteria

August 13, 2008

First Posted (Estimate)

August 14, 2008

Study Record Updates

Last Update Posted (Estimate)

June 29, 2015

Last Update Submitted That Met QC Criteria

June 1, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00003239

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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