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

Early Phase 1CompletedNCT00734994

Mark Dewhirst15 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Transitional Cell Carcinoma of Bladder Superficial Bladder Cancer

Interventions

Hyperthermia SystemDEVICE

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

Mitomycin CDRUG

40 mg in 40 ml sterile water instilled into bladder

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (1)

Duke University Medical Center

Durham, North Carolina, United States

Outcomes

Primary Outcomes

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.

Time frame: During Treatment Phase average 6 weeks

Secondary Outcomes

Median Recurrence Free-survival

Time to first recurrence of cancer in the bladder.

Time frame: Median follow-up 3.18 years

Data from ClinicalTrials.gov

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