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

Superficial Bladder Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00734994
• Other study ID #: Pro00003239
• Status: Completed
• Phase: Phase 0
• First received: May 4, 2008
• Last updated: June 1, 2015
• Start date: April 2008
• Est. completion date: March 2011

Study information

• Verified date: June 2015
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: March 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Transitional Cell
• Superficial Bladder Cancer
• Transitional Cell Carcinoma of Bladder
• Urinary Bladder Neoplasms

Intervention

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

Drug:
• Mitomycin C
40 mg in 40 ml sterile water instilled into bladder

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Mark Dewhirst

Country where clinical trial is conducted

United States, 

References & Publications (3)

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: — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Median Recurrence Free-survival	Time to first recurrence of cancer in the bladder.	Median follow-up 3.18 years	No