Clinical trial NCT00734994: Mitomycin C With Hyperthermia and Intravesical Mitomycin C to Treat Recurrent Bladder Cancer
Official title: Pilot Study of External Hyperthermia and Intravesical Mitomycin-C To Treat Recurrent Bladder Cancer After Resection and Standard Adjuvant Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Transitional Cell Carcinoma of Bladder
Superficial Bladder Cancer
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2008-08-14
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and Tolerability
timeFrame: During Treatment Phase average 6 weeks
Secondary outcomes:
measure: Median Recurrence Free-survival
timeFrame: Median follow-up 3.18 years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Zelko Vujaskovic, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Brant A Inman, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Juang T, Stauffer PR, Craciunescu OA, Maccarini PF, Yuan Y, Das SK, Dewhirst MW, Inman BA, Vujaskovic Z. Thermal dosimetry characteristics of deep regional heating of non-muscle invasive bladder cancer. Int J Hyperthermia. 2014 May;30(3):176-83. doi: 10.3109/02656736.2014.898338. Epub 2014 Mar 26.
citation: Yuan Y, Cheng KS, Craciunescu OI, Stauffer PR, Maccarini PF, Arunachalam K, Vujaskovic Z, Dewhirst MW, Das SK. Utility of treatment planning for thermochemotherapy treatment of nonmuscle invasive bladder carcinoma. Med Phys. 2012 Mar;39(3):1170-81. doi: 10.1118/1.3679839.
citation: Inman BA, Stauffer PR, Craciunescu OA, Maccarini PF, Dewhirst MW, Vujaskovic Z. A pilot clinical trial of intravesical mitomycin-C and external deep pelvic hyperthermia for non-muscle-invasive bladder cancer. Int J Hyperthermia. 2014 May;30(3):171-5. doi: 10.3109/02656736.2014.882021. Epub 2014 Feb 3.