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
Data Collection
Urogenital Diseases+8
+ Urinary Bladder Diseases
+ Urinary Bladder Neoplasms
Treatment Study
Summary
Study start date: October 1, 2009
Actual date on which the first participant was enrolled.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
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.242 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: * Diagnosis of non-muscle invasive bladder cancer * Recurrent disease after undergoing induction or maintenance therapy with bacillus Calmette-Guérin (BCG), meeting any 1 of the following criteria: * Stage Ta or T1 disease (grade 2 or 3) * Carcinoma in situ with stage Ta or T1 disease (grade 1, 2, or 3) * Carcinoma in situ alone * Has undergone a second resection of all T1 disease to exclude muscle invasive disease * No urothelial cell carcinoma (UCC) ≥ T2 * No recurrence of grade 1 UCC following BCG induction therapy * No UCC involving the prostatic urethra or upper urinary tract PATIENT CHARACTERISTICS: * WHO performance status 0-4 * WBC ≥ 3.0 x 10\^9/L * Absolute neutrophil count ≥ 1.5 x 10\^9/L * Hemoglobin ≥ 10 g/dL * Platelet count ≥ 100 x 10\^9/L * Serum creatinine \< 1.5 times upper limit of normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Normal kidneys and ureters on imaging CT scan within the past 12 months * Available for long-term follow-up with a life expectancy of the duration of the trial * Must be fit and willing to undergo a full or partial cystectomy * No known or suspected reduced bladder capacity (\< 250 mL) * No significant bleeding disorder * No other malignancy within the past 5 years except nonmelanomatous skin cancer cured by excision, adequately treated carcinoma in situ of the cervix, or DCIS/LCIS of the breast * No known allergy to mitomycin or bacillus Calmette-Guérin (BCG), or previously withdrawn from BCG treatment due to a related adverse event (e.g., systemic infection) * No active or intractable urinary tract infection * No urethral stricture or any situation impeding the insertion of a 20F catheter * No bladder diverticula \> 1 cm * No significant urinary incontinence * No concurrent implanted electronic devices (e.g., cardiac pacemakers) or metallic implants within the pelvis, lower torso, spine, hip, or upper femur * No immunocompromised state for any reason PRIOR CONCURRENT THERAPY: * At least 6 months since prior intravesical chemotherapy, except for single instillation post-transurethral resection * No prior pelvic irradiation * No prior hyperthermia in combination with intravesical mitomycin * Concurrent participation in other studies allowed * No current or long-term use of corticosteroids * No concurrent chemotherapy
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.Study Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 9 locations
Basingstoke and North Hampshire NHS Foundation Trust
Basingstoke, United KingdomOpen Basingstoke and North Hampshire NHS Foundation Trust in Google MapsQueen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
Birmingham, United KingdomLeeds Cancer Centre at St. James's University Hospital
Leeds, United KingdomUniversity Hospitals of Leicester NHS Trust
Leicester, United Kingdom