Urinary Bladder DiseasesPhase 3NCT00384891
Hyperthermia Treatment in Conjunction With Mitomycin C Versus Bacillus Calmette-Guérin Immunotherapy (BCG) for Superficial Bladder Cancer
A Phase 3 study testing Synergo + MMC and Bacillus Calmette-Guérin in people with Urinary Bladder Diseases and Urinary Bladder Neoplasms, run by Medical Enterprises Europe B.V. at 8 sites in 4 countries.
Trial summary
The study is designed to compare the efficacy and safety of 2 treatment types for the prevention of tumor recurrence of superficial bladder cancer: 1. A combination of bladder wall heating and local chemotherapy (Synergo) 2. Bacillus Calmette-Guérin (BCG) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Urinary Bladder Diseases, Urinary Bladder Neoplasms, Urinary Bladder Cancer
- What is being tested?
- Synergo + MMC and Bacillus Calmette-Guérin
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 190 participants
- Where
- 8 sitesin 4 countries
- Study dates
- Feb 2002to Dec 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
Who may be able to join
- Superficial TCC: Any G3 or any T1 and/or CIS
- Multifocal (>1) Ta lesions
- Multiple recurrences (>2) of Ta lesions in the last 24 months
- Complete tumor eradication must be confirmed
- WHO performance status 0-2 (Appendix V)
- Life expectancy of more than 24 months
- Patients willing to sign informed consent
Who cannot join
- Bladder tumors other than TCC
- Coexistence of another primary malignant tumor other than BCC of the skin
- TCC of the bladder involving the urethra or upper urinary tract
- Previous history of TCC stage T2 or higher
- Clinical presence or previous history of regional spreading or distant metastases
- Intravesical MMC treatments during the last 12 months
Show all 24Show fewer
- Previous intravesical BCG therapy (Any intravesical BCG therapy in the last 24 months, or More than 6 BCG intravesical instillations in the last 48 months.
- Previous pelvic radiotherapy or systemic chemotherapy
- Partial cystectomy
- Diverticle of bladder larger than 1cm in diameter
- Residual urine > 100cc measured by uroflowmetry
- Bladder volume < 150cc measured by ultrasound
- Urinary incontinence (more than one wet pad a day)
- Urethral stricture impeding 20F catheterization
- Urethral bleeding or persistent hematuria
- Active intractable or uncontrollable UTI
- Active tuberculosis or BCG infection
- Patients who experienced BCG life threatening sepsis
- Known allergy to MMC or BCG
- Known impaired immune response, positive HIV serology, patients receiving systemic steroids or immunosuppressive therapy
- Hematological disorders; leukocytes < 3500, platelets < 100,000
- Kidney or liver function disorders (more than 1.5 times upper normal limit)
- Pregnant or lactating women
- Patients who cannot be followed up properly or are unable to collaborate
Trial locations and contacts
8 sites in 4 countries.
8 sites in 4 countries
Israel3 sites
Bnai Zion Medical Center
Haifa
Wolfson Hospital
Holon
Hadassah University Hospital
Jerusalem
Italy3 sites
Galliera Hospital
Genova
Istituto Europeo del Oncologia
Milan
San Raffaele Hospital (HSR)
Milan
Netherlands1 site
Department of Urology, Radboud University Hospital
Nijmegen
About this study
Official title: A Randomized Controlled Study Comparing Adjuvant Hyperthermia Treatment in Conjunction With Mitomycin C Versus BCG Immunotherapy (BCG) Adjuvant Treatment in Patients With Superficial Transitional Cell Carcinoma of the Bladder (STCCB)
The study is designed to compare the efficacy and safety of 2 treatment types for the prevention of tumor recurrence of superficial bladder cancer:
- A combination of bladder wall heating and local chemotherapy (Synergo)
- Bacillus Calmette-Guérin (BCG)
Read the detailed description
The study is a randomized controlled study, designed to test the efficacy and safety of a new treatment modality for the prevention of tumor recurrence in superficial bladder cancer.
Patients must have their tumors surgically resected prior to study enrollment, and undergo a series of tests to prove their bladder is now free of tumor. Eligible patients will be randomly assigned to one of 2 treatment arms:
- A combination of bladder wall heating and local chemotherapy (Synergo)
- Bacillus Calmette-Guérin (BCG)
Patients will be treated during the first year of the study, and will be followed up for a total of 2 years. The follow up will include a visual evaluation of the patient's bladder by cystoscopy, a cytological examination of the urine (to look for malignant cells) and other additional exams. The patients' general welfare will be monitored through out the study.
The aim of this study is to compare the efficacy and safety of the novel treatment (Synergo) to that of the well-known BCG
- Conditions
- Urinary Bladder Diseases, Urinary Bladder Neoplasms, Urinary Bladder Cancer, Malignant Tumor of Urinary Bladder, Urologic Diseases, Urologic Neoplasms
- Being tested
- Synergo + MMC, Bacillus Calmette-Guérin
- Keywords
- Superficial urothelial cell carcinoma of bladder, NMIBC, Non Muscle Invasive Bladder Cancer, Hyperthermia, Bladder instillation, Mitomycin C, RITE, SHTC, Intravesical
- Medical subject headings
- Urinary Bladder Diseases, Urinary Bladder Neoplasms, Urologic Diseases, Urologic Neoplasms, Neoplasms, Neoplasms by Site, Non-Muscle Invasive Bladder Neoplasms, Hyperthermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Synergo + MMCDevice
Also called RITE, SHTC
Combined bladder wall hyperthermia and intravesical instillation with cooled Mitomycin-C
Bacillus Calmette-GuérinDrug
Also called BCG
Intravesical instillation with BCG (Bacillus Calmette-Guérin)
| Study group | Role | What they receive |
|---|---|---|
| Synergo + MMC | Experimental | Combined bladder wall hyperthermia and intravesical instillation with cooled Mitomycin-C Receives: Device: Synergo + MMC |
| Bacillus Calmette-Guérin | Active comparator | Intravesical instillation with BCG (Bacillus Calmette-Guérin) Receives: Drug: Bacillus Calmette-Guérin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence free survival
Recurrence free survival probability of STCCB in patients with pure (non-CIS) papillary tumor
Measured: 2 years
Secondary outcomes (3)
Proportion of complete response in CIS patients
Measured: 3 months
Progression rate (to disease stage>T1) and/or metastatic disease
Measured: 2 years
Local and systemic side effects, both subjective and objective
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2006 (estimated)
- Study startFeb 2002
- Primary completionDec 2013
- Study completionDec 2013
Why it stopped: slow accrual
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 Urinary Bladder DiseasesStudies 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
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 190 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical Enterprises Europe B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alfred A Witjes, MD PhD, Principal investigator, Department of Urology, Radboud University Hospital, Nijmegen, The Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00384891
- Sponsor's protocol ID
- 102.1
- Status last verified
- Oct 2014
- First submitted
- 5 Oct 2006
- Last updated
- 7 Oct 2014
- Results posted
- No
Publications
Arends TJ, Nativ O, Maffezzini M, de Cobelli O, Canepa G, Verweij F, Moskovitz B, van der Heijden AG, Witjes JA. Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guerin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non-Muscle-invasive Bladder Cancer. Eur Urol. 2016 Jun;69(6):1046-52. doi: 10.1016/j.eururo.2016.01.006. Epub 2016 Jan 20.
PubMed 26803476
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Study Comparing Adjuvant Hyperthermia Treatment in Conjunction With Mitomycin C Versus BCG Immunotherapy (BCG) Adjuvant Treatment in Patients With Superficial Transitional Cell Carcinoma of the Bladder (STCCB)
- ClinicalTrials.gov ID
- NCT00384891
- Acronym / sponsor ID
- 102.1
- Conditions
- Urinary Bladder Diseases, Urinary Bladder Neoplasms, Urinary Bladder Cancer, Malignant Tumor of Urinary Bladder, Urologic Diseases, Urologic Neoplasms
- Keywords
- Superficial urothelial cell carcinoma of bladder, NMIBC, Non Muscle Invasive Bladder Cancer, Hyperthermia, Bladder instillation, Mitomycin C, RITE, SHTC
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow accrual
- Enrolment
- 190 participants (actual)
- Lead sponsor
- Medical Enterprises Europe B.V.Industry (pharma, biotech, devices)
- Study start
- Feb 2002
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 6 Oct 2006 (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.
The study is designed to compare the efficacy and safety of 2 treatment types for the prevention of tumor recurrence of superficial bladder cancer:
- A combination of bladder wall heating and local chemotherapy (Synergo)
- Bacillus Calmette-Guérin (BCG)
Detailed description
The study is a randomized controlled study, designed to test the efficacy and safety of a new treatment modality for the prevention of tumor recurrence in superficial bladder cancer.
Patients must have their tumors surgically resected prior to study enrollment, and undergo a series of tests to prove their bladder is now free of tumor. Eligible patients will be randomly assigned to one of 2 treatment arms:
- A combination of bladder wall heating and local chemotherapy (Synergo)
- Bacillus Calmette-Guérin (BCG)
Patients will be treated during the first year of the study, and will be followed up for a total of 2 years. The follow up will include a visual evaluation of the patient's bladder by cystoscopy, a cytological examination of the urine (to look for malignant cells) and other additional exams. The patients' general welfare will be monitored through out the study.
The aim of this study is to compare the efficacy and safety of the novel treatment (Synergo) to that of the well-known BCG
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Synergo + MMC | Experimental | Device: Synergo + MMCCombined bladder wall hyperthermia and intravesical instillation with cooled Mitomycin-C |
| Bacillus Calmette-Guérin | Active comparator | Drug: Bacillus Calmette-GuérinIntravesical instillation with BCG (Bacillus Calmette-Guérin) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Superficial TCC: Any G3 or any T1 and/or CIS
- Multifocal (>1) Ta lesions
- Multiple recurrences (>2) of Ta lesions in the last 24 months
- Complete tumor eradication must be confirmed
- WHO performance status 0-2 (Appendix V)
Key exclusion criteria (24 listed)
- Bladder tumors other than TCC
- Coexistence of another primary malignant tumor other than BCC of the skin
- TCC of the bladder involving the urethra or upper urinary tract
- Previous history of TCC stage T2 or higher
- Clinical presence or previous history of regional spreading or distant metastases
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 |
|---|---|---|
| Synergo + MMCAlso: RITE, SHTCCombined bladder wall hyperthermia and intravesical instillation with cooled Mitomycin-C | Device | Synergo + MMC |
| Bacillus Calmette-GuérinAlso: BCGIntravesical instillation with BCG (Bacillus Calmette-Guérin) | Drug | Bacillus Calmette-Guérin |
Primary outcome
Recurrence free survival
Time frame: 2 years
Recurrence free survival probability of STCCB in patients with pure (non-CIS) papillary tumor
3 secondary outcomes
Proportion of complete response in CIS patients
Time frame: 3 months
Progression rate (to disease stage>T1) and/or metastatic disease
Time frame: 2 years
Local and systemic side effects, both subjective and objective
Time frame: 2 years
Results and safety
The study was stopped early (reason given: slow accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2014.
- Derived from this study: PubMed 26803476Arends TJ, Nativ O, Maffezzini M, de Cobelli O, Canepa G, Verweij F, Moskovitz B, van der Heijden AG, Witjes JA. Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guerin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non-Muscle-invasive Bladder Cancer. Eur Urol. 2016 Jun;69(6):1046-52. doi: 10.1016/j.eururo.2016.01.006. Epub 2016 Jan 20.
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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.
Alfred A Witjes, MD PhD principal investigator
Department of Urology, Radboud University Hospital, Nijmegen, The Netherlands
8 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Synergo + MMC and Bacillus Calmette-Guérin in people with Urinary Bladder Diseases and Urinary Bladder Neoplasms, run by Medical Enterprises Europe B.V. at 8 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 24 exclusion criteria. 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: stopped early, as of the sponsor's last update on 7 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Israel, Italy, Austria, Netherlands. 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?
The study was stopped early (reason given: slow accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence free survival (time frame: 2 years). 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 NCT00384891, 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 7 Oct 2014.