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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mark Dewhirst, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00734994
First received: May 4, 2008
Last updated: December 14, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Transitional Cell Carcinoma of Bladder
Superficial Bladder Cancer
Device: Hyperthermia System
Drug: Mitomycin C
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of External Hyperthermia and Intravesical Mitomycin-C To Treat Recurrent Bladder Cancer After Resection and Standard Adjuvant Therapy

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Safety [ Time Frame: During Treatment Phase average 6 weeks ] [ Designated as safety issue: Yes ]
    Number of patient treatments stopped due to safety concerns including side effect such as heat sensations or burning in the pelvis, intolerance to heat, weight of the water bolus on the abdomen, or supine position.


Secondary Outcome Measures:
  • Time to Second Recurrence [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: April 2008
Study Completion Date: March 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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
Other Name: BSD 2000 Hyperthermia system
Drug: Mitomycin C
40 mg in 40 ml sterile water instilled into bladder
Other Name: Mutamycin

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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00734994

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Mark Dewhirst
Investigators
Principal Investigator: Zeljko Vujaskovic, MD, PhD Duke University
  More Information

No publications provided

Responsible Party: Mark Dewhirst, Professor, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00734994     History of Changes
Other Study ID Numbers: Pro00003239
Study First Received: May 4, 2008
Results First Received: August 1, 2011
Last Updated: December 14, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma
Carcinoma, Transitional Cell
Fever
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Body Temperature Changes
Signs and Symptoms
Mitomycins
Mitomycin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 14, 2014