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

Primary Purpose

Transitional Cell Carcinoma of Bladder, Superficial Bladder Cancer

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Hyperthermia System

Mitomycin C

About this trial

This is an interventional treatment trial for Transitional Cell Carcinoma of Bladder

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Duke University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hyperthermia system, Mitomycin C

Arm 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Median Recurrence Free-survival

Time to first recurrence of cancer in the bladder.

Full Information

NCT ID

NCT00734994

First Posted

May 4, 2008

Last Updated

June 1, 2015

Sponsor

Mark Dewhirst

1. Study Identification

Unique Protocol Identification Number

NCT00734994

Brief Title

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

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Completed

Study Start Date

April 2008 (undefined)

Primary Completion Date

February 2011 (Actual)

Study Completion Date

March 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Mark Dewhirst

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Transitional Cell Carcinoma of Bladder, Superficial Bladder Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Hyperthermia system, Mitomycin C

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

Hyperthermia System

Other Intervention Name(s)

BSD 2000 Hyperthermia system

Intervention Description

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

Drug

Intervention Name(s)

Mitomycin C

Other Intervention Name(s)

Mutamycin

Intervention Description

40 mg in 40 ml sterile water instilled into bladder

Primary Outcome Measure Information:

Title

Safety and Tolerability

Description

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.

Time Frame

During Treatment Phase average 6 weeks

Secondary Outcome Measure Information:

Title

Median Recurrence Free-survival

Description

Time to first recurrence of cancer in the bladder.

Time Frame

Median follow-up 3.18 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Zelko Vujaskovic, MD

Organizational Affiliation

Duke University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Brant A Inman, MD, MS

Organizational Affiliation

Duke University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Duke University Medical Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

24669804

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.

Results Reference

background

PubMed Identifier

22380348

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.

Results Reference

background

PubMed Identifier

24490762

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.

Results Reference

result

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

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