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

Mark Dewhirst

Status and phase: Completed; Early Phase 1

Conditions: Superficial Bladder Cancer; Transitional Cell Carcinoma of Bladder

Treatments: Drug: Mitomycin C; Device: Hyperthermia System

Study type: Interventional

Funder types: Other

Identifiers

NCT00734994

Pro00003239

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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15 participants in 1 patient group

Hyperthermia system, Mitomycin C

Experimental group

Description:

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.

Treatment:

Device: Hyperthermia System

Drug: Mitomycin C