HYMN: a trial comparing hyperthermia and mitomycin chemotherapy with a second BCG treatment, or other standard treatment, for bladder cancer that has come back

A randomised controlled phase III trial comparing hyperthermia plus mitomycin to a second course of Bacillus Calmette-Guerin (BCG) or standard therapy in patients with recurrence of non-muscle invasive bladder cancer following induction or maintenace BCG therapy

Status

Active, not recruiting

Phases

Phase 3

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN85785327

Enrollment

242

Registered

2009-05-28

Start date

2009-06-01

Completion date

Unknown

Last updated

2020-07-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-muscle invasive bladder cancer Cancer Malignant neoplasm of bladder

Interventions

Current interventions as of 11/02/2013: Experimental Arm: Patients will receive six weekly induction instillations of hyperthermia plus mitomycin (HM) using the Synergo® System, follow

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Both males and females, age >=18 years 2. Previous BCG induction or maintenance therapy for non-muscle-invasive bladder cancer (NMIBC) 3. Recurrence of disease following induction or maintenance BCG defined as: 3.1. Grade 3 or Grade 2, stage Ta or T1 disease 3.2. Carcinoma in situ (CIS) with Grade 3, Grade 2 or Grade 1 stage Ta or T1 disease 3.3. CIS alone 4. Have undergone a re-resection of all T1 disease to exclude muscle invasive disease 5. World Health Organization (WHO) performance status 0, 1, 2, 3 or 4 6. Normal kidneys and ureters on imaging* study within the past 12 months 7. Pre-treatment haematology and biochemistry values within acceptable limits: 7.1. Haemoglobin >=10 g/dl 7.2. Platelets >=100 x 10^9/l 7.3. White blood cells (WBC) >=3.0 x 10^9/l or absolute neutrophil count (ANC) >=1.5 x 10^9/l 7.4. Serum creatinine <1.5 x Upper Normal Limit (UNL) 8. Negative pregnancy test for women of child-bearing potential 9. Available for long-term follow-up 10. Unfit or unwilling to have a cystectomy 11. Written informed consent *Imaging of high risk recurrent UCC by computerised tomography (CT) scan is routinely performed in some centres and is recommended as good practice in this trial.

Exclusion criteria

Exclusion criteria: Current exclusion criteria as of 11/02/2013: 1. Recurrence of Grade 1 UCC following BCG induction 2. Previous intravesical chemotherapy in the past 6 months, other than single instillation post-TUR. 3. UCC involving the prostatic urethra or upper urinary tract 4. >=T2 UCC 5. Known or suspected reduced bladder capacity (1 cm 15. Significant urinary incontinence 16. History of pelvic irradiation 17. Patients with implanted electronic devices (such as cardiac pacemakers) or metallic implants within the pelvis, lower torso, spine, hip or upper femur 18. Suitable and willing to have or have had a full or partial cystectomy Previous exclusion criteria until 11/02/2013: 1. Recurrence of Grade 1 UCC following BCG induction 2. Previous intravesical chemotherapy in the past 6 months, other than single instillation post-TUR. 3. UCC involving the prostatic urethra or upper urinary tract 4. >=T2 UCC 5. Known or suspected reduced bladder capacity (1 cm 15. Significant urinary incontinence

Design outcomes

Primary

Measure	Time frame
Current primary outcome measures as of 11/02/2013: 1. Disease-free survival. For patients without CIS at baseline and those with CIS at baseline but not at the 3-month surveillance visit, this is defined as the interval in whole days between the date of randomisation into the trial and the earliest of date of detection of recurrent disease, or date of death from any cause. For patients with CIS at baseline and at the 3-month surveillance visit, this is defined as the interval in whole days between the date of randomisation and the date of their 3-month surveillance visit. Disease recurrence is defined as the presence of urothelial cell carcinoma or positive cytology. Disease progression is defined as T2 disease or evidence extravesical disease. For those patients who do not have recurrent disease or die during the course of the trial, disease-free survival times will be censored at the last follow-up date. Patients who experience a distant upper-tract recurrence will be censored at the last available assessment. Disease-free survival will be followed-up for 2 years from the first treatment. 2. Complete-response rate at 3 months. For patients with CIS at randomisation, complete response at 3 months is defined as absence of visible tumour recurrence at cystoscopy, negative cytology and no evidence of CIS on random (4 quadrant) biopsy of the bladder. Previous primary outcome measures until 11/02/2013: 1. Disease-free survival. Defined as the interval in whole days between the date of randomisation into the trial and the earliest of date of detection of recurrent disease, or date of death from any cause. This will also include the interval in whole days between the date proved tumour free (by cystoscopy, negative cytology and biopsy) and the earliest of date of detection of recurrent disease, or date of death from any cause in patients with CIS at randomisation. Disease recurrence is defined as the presenc	—

Measure

Time frame

Current primary outcome measures as of 11/02/2013: 1. Disease-free survival. For patients without CIS at baseline and those with CIS at baseline but not at the 3-month surveillance visit, this is defined as the interval in whole days between the date of randomisation into the trial and the earliest of date of detection of recurrent disease, or date of death from any cause. For patients with CIS at baseline and at the 3-month surveillance visit, this is defined as the interval in whole days between the date of randomisation and the date of their 3-month surveillance visit. Disease recurrence is defined as the presence of urothelial cell carcinoma or positive cytology. Disease progression is defined as T2 disease or evidence extravesical disease. For those patients who do not have recurrent disease or die during the course of the trial, disease-free survival times will be censored at the last follow-up date. Patients who experience a distant upper-tract recurrence will be censored at the last available assessment. Disease-free survival will be followed-up for 2 years from the first treatment. 2. Complete-response rate at 3 months. For patients with CIS at randomisation, complete response at 3 months is defined as absence of visible tumour recurrence at cystoscopy, negative cytology and no evidence of CIS on random (4 quadrant) biopsy of the bladder. Previous primary outcome measures until 11/02/2013: 1. Disease-free survival. Defined as the interval in whole days between the date of randomisation into the trial and the earliest of date of detection of recurrent disease, or date of death from any cause. This will also include the interval in whole days between the date proved tumour free (by cystoscopy, negative cytology and biopsy) and the earliest of date of detection of recurrent disease, or date of death from any cause in patients with CIS at randomisation. Disease recurrence is defined as the presenc

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Secondary

Measure	Time frame
1. Progression-free survival. Defined as the interval in whole days between the date of randomisation into the trial and the earliest of date of detection of disease progression, or date of death from any cause. Disease progression is defined as stage T2 disease or greater confirmed by histopathology following TUR (>=pT2). For those patients who do not experience disease progression or die during the course of the trial, progression-free survival times will be censored at the last follow-up date. Patients who experience a distant upper-tract recurrence will be censored at the last available assessment. 2. Overall survival. Defined as the interval in whole days between the date of randomisation into the trial and date of death from any cause; patients who do not die during the course of the trial will be censored at the last follow-up date. 3. Disease-specific survival. Defined as the interval in whole days between the date of randomisation into the trial and date of death due to bladder cancer. Patients who do not die during the course of the trial will be censored at the last follow-up date. Patients who die of other causes will be censored at date of death due to other cause. 4. Recurrence-free survival. Recurrence-free survival will be measured in patients with papillary disease only. It is defined in the same way as disease-free survival, with the important distinction that CIS at the first three-month post-treatment visit will not be included as an event, but rather considered a treatment failure and will be censored. Patients who entered with CIS, became negative at first control, will be also followed up for recurrence free from first control. 5. Safety and tolerability of HM. Safety and tolerability will be reported in terms of the frequency, severity and nature of adverse events, and the treatment received. 6. Quality of life. Quality of life will be assessed at trial entry and	—

Measure

Time frame

1. Progression-free survival. Defined as the interval in whole days between the date of randomisation into the trial and the earliest of date of detection of disease progression, or date of death from any cause. Disease progression is defined as stage T2 disease or greater confirmed by histopathology following TUR (>=pT2). For those patients who do not experience disease progression or die during the course of the trial, progression-free survival times will be censored at the last follow-up date. Patients who experience a distant upper-tract recurrence will be censored at the last available assessment. 2. Overall survival. Defined as the interval in whole days between the date of randomisation into the trial and date of death from any cause; patients who do not die during the course of the trial will be censored at the last follow-up date. 3. Disease-specific survival. Defined as the interval in whole days between the date of randomisation into the trial and date of death due to bladder cancer. Patients who do not die during the course of the trial will be censored at the last follow-up date. Patients who die of other causes will be censored at date of death due to other cause. 4. Recurrence-free survival. Recurrence-free survival will be measured in patients with papillary disease only. It is defined in the same way as disease-free survival, with the important distinction that CIS at the first three-month post-treatment visit will not be included as an event, but rather considered a treatment failure and will be censored. Patients who entered with CIS, became negative at first control, will be also followed up for recurrence free from first control. 5. Safety and tolerability of HM. Safety and tolerability will be reported in terms of the frequency, severity and nature of adverse events, and the treatment received. 6. Quality of life. Quality of life will be assessed at trial entry and

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Countries

United Kingdom

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Feb 4, 2026