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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Transitional Cell Carcinoma of Bladder, Superficial Bladder Cancer

Intervention / Treatment
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* Device: Hyperthermia System
* Drug: Mitomycin C


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyperthermia system, Mitomycin C<br>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<br>* 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<br>* Other names: BSD 2000 Hyperthermia system;Drug: Mitomycin C<br>* 40 mg in 40 ml sterile water instilled into bladder<br>* Other names: Mutamycin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | 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 to first recurrence of cancer in the bladder. | Median follow-up 3.18 years |