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
- 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.
- 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
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Disease-free survival time
John Kelly, MD
University College London Hospitals