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

NCT ID: NCT00734994

Last Updated: 2015-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2011-03-31

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.

Conditions

Transitional Cell Carcinoma of Bladder; Superficial Bladder Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Hyperthermia system, Mitomycin C

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.

Group Type: EXPERIMENTAL

Hyperthermia System

Intervention Type: DEVICE

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 C

Intervention Type: DRUG

40 mg in 40 ml sterile water instilled into bladder

Interventions

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

Intervention Type: DEVICE

Mitomycin C

40 mg in 40 ml sterile water instilled into bladder

Intervention Type: DRUG

Other Intervention Names

BSD 2000 Hyperthermia system; Mutamycin

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mark Dewhirst

OTHER

Sponsor Role: lead

Responsible Party

Mark Dewhirst

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Zelko Vujaskovic, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Brant A Inman, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 24669804 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22380348 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24490762 (View on PubMed)

Other Identifiers

Pro00003239

Identifier Type: -

Identifier Source: org_study_id