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

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. Read our disclaimer for details. Identifier: NCT00734994
Recruitment Status : Completed
First Posted : August 14, 2008
Results First Posted : August 30, 2011
Last Update Posted : June 29, 2015
Information provided by (Responsible Party):
Mark Dewhirst, Duke University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Transitional Cell Carcinoma of Bladder Superficial Bladder Cancer Device: Hyperthermia System Drug: Mitomycin C Early Phase 1

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  (Clinical Trial)
Actual Enrollment : 15 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study of External Hyperthermia and Intravesical Mitomycin-C To Treat Recurrent Bladder Cancer After Resection and Standard Adjuvant Therapy
Study Start Date : April 2008
Actual Primary Completion Date : February 2011
Actual Study Completion Date : March 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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 Name: BSD 2000 Hyperthermia system
Drug: Mitomycin C
40 mg in 40 ml sterile water instilled into bladder
Other Name: Mutamycin

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Median Recurrence Free-survival [ Time Frame: Median follow-up 3.18 years ]
    Time to first recurrence of cancer in the bladder.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00734994

United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Mark Dewhirst
Principal Investigator: Zelko Vujaskovic, MD Duke University
Principal Investigator: Brant A Inman, MD, MS Duke University

Publications of Results:
Other Publications:
Responsible Party: Mark Dewhirst, Professor, Duke University Identifier: NCT00734994     History of Changes
Other Study ID Numbers: Pro00003239
First Posted: August 14, 2008    Key Record Dates
Results First Posted: August 30, 2011
Last Update Posted: June 29, 2015
Last Verified: June 2015

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Body Temperature Changes
Signs and Symptoms
Antibiotics, Antineoplastic
Antineoplastic Agents
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors