Bladder CancerPhase 3NCT01094964
Hyperthermia and Mitomycin C, Bacillus Calmette-Guerin, or Standard Therapy as Second-Line Therapy in Treating Patients With Recurrent Bladder Cancer
A Phase 3 study testing BCG solution, recombinant interferon alfa and epirubicin hydrochloride in people with Bladder Cancer, run by Cancer Research Campaign Clinical Trials Centre at 9 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bladder Cancer
- What is being tested?
- BCG solution, recombinant interferon alfa and epirubicin hydrochloride
- Type of treatment
- Surgery or procedure
- How many people
- 242 participants
- Where
- 9 sitesUnited Kingdom
- Study dates
- Oct 2009to Oct 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United Kingdom9 sites, 9 recruiting
- Recruiting
Basingstoke and North Hampshire NHS Foundation Trust
Basingstoke, England, RG24 9NA
Contact Person, 44-1256-314-700
- Recruiting
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
Birmingham, England, B15 2TH
Contact Person, 44-121-472-1311
- Recruiting
University Hospital of Wales
Cardiff, Wales, CF14 4XN
Contact Person, 44-29-2074-7747
- Recruiting
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, LS9 7TF
Contact Person, 44-113-243-3144
- Recruiting
University Hospitals of Leicester NHS Trust
Leicester, England, LE1 5WW
Contact Person, 44-300-303-1573
- Recruiting
St. George's Hospital
London, England, SW17 0QT
Contact Person, 44-208-672-1255
- Recruiting
University College of London Hospitals
London, England, WC1E 6AU
Contact Person, 44-845-1555-000
- Recruiting
South Manchester University Hospital
Manchester, England, M20 2LR
Contact Person, 44-161-998-7070
- Recruiting
James Cook University Hospital
Middlesbrough, England, TS19 8PE
Contact Person, 44-1609-779-911
About this study
Official title: 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
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.
Read the 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
- Being tested
- BCG solution, recombinant interferon alfa, epirubicin hydrochloride, mitomycin C, laboratory biomarker analysis
- Keywords
- recurrent bladder cancer, stage 0 bladder cancer, stage I bladder cancer, adenocarcinoma of the bladder, squamous cell carcinoma of the bladder
- Medical subject headings
- Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BCG solutionBiological
recombinant interferon alfaBiological
epirubicin hydrochlorideDrug
mitomycin CDrug
laboratory biomarker analysisOther
hyperthermia treatmentProcedure or surgery
quality-of-life assessmentProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-free survival time
Complete response rate at 3 months in patients with carcinoma in situ
Secondary outcomes (8)
Recurrence-free survival time
Progression-free survival time
Overall survival time
Disease-specific survival time
Safety and tolerability
Quality of Life
Cost effectiveness
Biomarkers of response to standard and investigational treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2010 (estimated)
- Study startOct 2009
- Primary completionOct 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 242 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cancer Research Campaign Clinical Trials Centre
- Sponsor type
- University, hospital or other
- Investigators
- John Kelly, MD, Principal investigator, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01094964
- Sponsor's protocol ID
- CRC-TU-BL3010-HYMN
- Other IDs
- CDR0000668528, ISRCTN85785327, EUDRACT-2008-005428-99, EU-21015, UCL-08/0365, KYOWA-CRC-TU-BL3010-HYMN, MREC-09/H0717/56
- Status last verified
- Mar 2010
- First submitted
- 26 Mar 2010
- Last updated
- 12 Aug 2013
- Results posted
- No
Publications
Tan WS, Panchal A, Buckley L, Devall AJ, Loubiere LS, Pope AM, Feneley MR, Cresswell J, Issa R, Mostafid H, Madaan S, Bhatt R, McGrath J, Sangar V, Griffiths TRL, Page T, Hodgson D, Datta SN, Billingham LJ, Kelly JD. Radiofrequency-induced Thermo-chemotherapy Effect Versus a Second Course of Bacillus Calmette-Guerin or Institutional Standard in Patients with Recurrence of Non-muscle-invasive Bladder Cancer Following Induction or Maintenance Bacillus Calmette-Guerin Therapy (HYMN): A Phase III, Open-label, Randomised Controlled Trial. Eur Urol. 2019 Jan;75(1):63-71. doi: 10.1016/j.eururo.2018.09.005. Epub 2018 Sep 28.
PubMed 30274699
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01094964
- Acronym / sponsor ID
- CRC-TU-BL3010-HYMN
- Conditions
- Bladder Cancer
- Keywords
- recurrent bladder cancer, stage 0 bladder cancer, stage I bladder cancer, adenocarcinoma of the bladder, squamous cell carcinoma of the bladder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 242 participants (estimated)
- Lead sponsor
- Cancer Research Campaign Clinical Trials CentreUniversity, hospital or other
- Study start
- Oct 2009
- Primary completion
- Oct 2013 (estimated)
- First posted
- 29 Mar 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BCG solution | Biological | – |
| recombinant interferon alfa | Biological | – |
| epirubicin hydrochloride | Drug | – |
| mitomycin C | Drug | – |
| laboratory biomarker analysis | Other | – |
| hyperthermia treatment | Procedure or surgery | – |
| quality-of-life assessment | Procedure or surgery | – |
Primary outcome
Disease-free survival time
Complete response rate at 3 months in patients with carcinoma in situ
8 secondary outcomes
Recurrence-free survival time
Progression-free survival time
Overall survival time
Disease-specific survival time
Safety and tolerability
Quality of Life
Cost effectiveness
Biomarkers of response to standard and investigational treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2013.
- Derived from this study: PubMed 30274699Tan WS, Panchal A, Buckley L, Devall AJ, Loubiere LS, Pope AM, Feneley MR, Cresswell J, Issa R, Mostafid H, Madaan S, Bhatt R, McGrath J, Sangar V, Griffiths TRL, Page T, Hodgson D, Datta SN, Billingham LJ, Kelly JD. Radiofrequency-induced Thermo-chemotherapy Effect Versus a Second Course of Bacillus Calmette-Guerin or Institutional Standard in Patients with Recurrence of Non-muscle-invasive Bladder Cancer Following Induction or Maintenance Bacillus Calmette-Guerin Therapy (HYMN): A Phase III, Open-label, Randomised Controlled Trial. Eur Urol. 2019 Jan;75(1):63-71. doi: 10.1016/j.eururo.2018.09.005. Epub 2018 Sep 28.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
Birmingham, United Kingdom
John Kelly, MD principal investigator
University College London Hospitals
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing BCG solution, recombinant interferon alfa and epirubicin hydrochloride in people with Bladder Cancer, run by Cancer Research Campaign Clinical Trials Centre at 9 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Disease-free survival time. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01094964, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2013.