NCT01094964

Hyperthermia and Mitomycin C, Bacillus Calmette-Guerin, or Standard Therapy as Second-Line Therapy in Treating Patients With Recurrent Bladder Cancer

HYMN: A Randomized Controlled Phase III Trial Comparing Hyperthermia Plus Mitomycin to a Second Course of Bacillus Calmette-Guerin or Standard Therapy in Patients With Recurrence of Non-Muscle Invasive Bladder Cancer Following Induction or Maintenance Bacillus Calmette-Guerin Therapy

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 242 (estimated)
• Sponsor: Cancer Research Campaign Clinical Trials Centre · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Hyperthermia therapy kills tumor cells by heating them to several degrees above normal body temperature. Drugs used in chemotherapy, such as mitomycin C and epirubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as bacillus calmette-guerin (BCG) and interferon alfa, may stimulate the immune system in different ways and stop tumor cells from growing. It is not yet known whether giving hyperthermia together with mitomycin C is more effective than giving BCG or standard therapy as second-line therapy in treating patients with recurrent bladder cancer. PURPOSE: This randomized phase III trial is studying how well hyperthermia given together with mitomycin C works compared with BCG or standard therapy as second-line therapy in treating patients with recurrent bladder cancer.

Detailed description

OBJECTIVES: Primary * To determine whether hyperthermia in combination with mitomycin C versus bacillus Calmette-Guerin (BCG) or standard therapy as second-line therapy is effective in patients with recurrent non-muscle invasive bladder cancer following induction or maintenance therapy with BCG. * To compare disease-free survival time in all patients. * To compare complete response rate at 3 months in patients with carcinoma in situ. Secondary * To compare progression-free survival, overall survival, safety and tolerability of treatments, quality of life, cost, and cost-effectiveness in these patients. * To assess biomarkers of response to standard and investigational treatment. OUTLINE: This is a multicenter study. Patients are stratified according to presence of carcinoma in situ (yes vs no), prior bacillus Calmette-Guérin (BCG) therapy (induction vs maintenance), and participating center. Patients are randomized to 1 of 2 treatment arms. * Arm I (experimental): Patients receive intravesical mitomycin C over two 30-minute instillations per session, and bladder hyperthermia (42 +/-2°C) is delivered in combination with each instillation. The suspension is maintained in the bladder for up to 2 hours. Treatment repeats once a week for 6 weeks followed by a 6-week rest period. Patients who are disease-free proceed to maintenance therapy consisting of one instillation of mitomycin C with bladder hyperthermia every 6 weeks for 1 year and then once every 8 weeks for 1 year. Patients who are disease-free at 24 months may continue treatment at the discretion of the clinician. * Arm II (control): Patients receive 1 of the following treatment regimens depending on prior BCG treatment. * Second course of BCG therapy (patients who failed previous induction BCG): Patients receive intravesical BCG (1 instillation) once a week for 6 weeks. The suspension is maintained in the bladder for up to 2 hours. Patients then receive maintenance therapy consisting of BCG once a week for 3 weeks in months 3, 6, 12, 18, and 24. Patients who are disease-free at 24 months may continue treatment at the discretion of the clinician. * Standard therapy (patients who failed previous maintenance BCG): Patients receive standard therapy for BCG failure as defined by their treating centers. Standard therapy may include intravesical BCG alone, intravesical mitomycin C alone, intravesical epirubicin hydrochloride alone, or intravesical BCG in combination with interferon alpha. All patients undergo cystoscopic surveillance with or without a biopsy every 3 months for 2 years. Urine, blood, and tissue samples are collected periodically for biomarker laboratory studies. Patients complete quality of life questionnaires (EORTC QLQ-BLS24, QLQ-C30, and EQ5D) at baseline, at 12 weeks, and at 6, 9, and 12 months. After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months thereafter. Peer Reviewed and Funded or Endorsed by Cancer Research UK

Conditions

• Bladder Cancer

Interventions

Type	Name	Description
BIOLOGICAL	BCG solution
BIOLOGICAL	recombinant interferon alfa
DRUG	epirubicin hydrochloride
DRUG	mitomycin C
OTHER	laboratory biomarker analysis
PROCEDURE	hyperthermia treatment
PROCEDURE	quality-of-life assessment

Timeline

• Start date: 2009-10-01
• Primary completion: 2013-10-01
• First posted: 2010-03-29
• Last updated: 2013-08-12

Locations

9 sites across 1 country: United Kingdom