Bladder CancerPhase 3NCT02471495
RITE-EUROPE (Radiofrequency-Induced Thermochemotherapy Effect-EUROPE)
A Phase 3 study testing Synergo® RITE + MMC in people with Bladder Cancer, run by Medical Enterprises Europe B.V..
Trial summary
This multicenter, prospective, single-arm, phase 3 study will assess the proportion of disease-free patients, starting from administration of the first study treatment to at least 12-months after the first treatment, and up to 2 years (the latter only in patients choosing to participate in longer-term… 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?
- Synergo® RITE + MMC
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2016to Jan 2020
- 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
- Patients with CIS, with or without coexisting papillary NMIBC, who either:
- fail to achieve a disease-free status by 6 months after initial BCG therapy, with maintenance or re-induction at 3 months due to either persistent or rapidly recurrent disease, or
- experience a worsening in NMIBC state following initial BCG therapy presenting with a new NMIBC instance, other than TaLG.
- All clinical, intra-operative and pathological items for the EAU risk stratification must be documented including a bladder map.
- Patients with papillary disease must have undergone a repeat TUR:
- if the initial TUR was incomplete.
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- if there was no muscle in the specimen after the initial TUR (except in TaLG tumors).
- in all T1 tumors. TUR of T1 sites must include muscle.
- in all HG tumors > 3cm.
- CT-IVU or IVU confirmation of absence of tumor(s) in the upper tract, kidney and ureters performed within 6 months before the treatment initiation in selected cases as recommended in latest EAU guidelines published prior to screening. If IVU protocol not available or contrast allergy/poor renal function preclude such imaging, then non-contrast CT or MRI of the abdomen/pelvis within the same timeframe will suffice.
- Visual inspection to exclude urothelial carcinoma (UC) in the urethra during cystoscopy.
- Biopsy of the prostatic urethra in male patients prior to recruitment to exclude UC of the prostatic urethra, in patients with:
- tumor of trigone,
- tumor of bladder neck, or
- abnormal prostatic urethra
- All patients must have urine cytology collected from either voided urine or bladder wash within the screening period prior to recruitment.
- All patients must have prostatic urethral biopsies collected within the screening period prior to recruitment.
- Age ≥ 18 yrs.
- Normal kidneys and ureters.
- Pre-treatment hematology and biochemistry values within the limits:
- Hemoglobin ≥ 10 g/dl
- Platelets ≥ 150 x 10^9/L
- WBC ≥ 3.0 x 10^9/L
- ANC ≥ 1.5 x 10^9/L
- Serum creatinine < 1.5 x ULN
- SGOT < 1.5 x ULN
- SGPT < 1.5 x ULN
- Alkaline phosphatase < 1.5 x ULN
- Negative pregnancy test for women of childbearing potential.
- A life expectancy at least of the duration of the study (up to 13 months).
- Patients unfit or unwilling to have a full or partial (if appropriate) cystectomy.
- Signed informed consent.
Who cannot join
- Non-UC tumor of the urinary tract.
- Upper tract and intramural tumors (e.g., in ostium).
- Positive selective cytology from the upper tract.
- History of stage > T1 UC.
- Papillary tumor in repeat TUR in patients diagnosed with HG > 3cm and/or T1 in the initial TUR.
- Papillary tumor ≥ T1 in repeat TUR
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- Known or suspected reduced bladder capacity. Patients will have a US estimation of maximum bladder capacity or void spontaneously the maximum they can retain in their bladder, and this will be used to determine urine volume. A minimum volume of 250 ml is required.
- Bleeding disorder.
- Macrohematuria of ≥ 250 RBC/uL or equivalent (e.g., > "+++" erythrocytes in a dipstick analysis) within 4 weeks before treatment start.
- Lactating women.
- Women of childbearing potential unwilling or unable to use adequate contraception if sexually active.
- More than a maintenance dose of oral corticosteroids (maintenance dose is defined as the same dose regimen over the past 6 months for a condition requiring continual corticosteroid treatment) or patients with an immunocompromised state for any reason.
- More than low-dose methotrexate (>17.5 mg once a week).
- Other malignancy within the past 5 years, except: non-melanomatous skin cancer cured by excision, surgically treated carcinoma in situ of the cervix or ductal CIS (DCIS)/lobular CIS (LCIS) of the breast or stable prostate cancer (under active surveillance or hormone control) with a life expectancy of more than 5 years.
- Any known allergy (e.g., to MMC) or adverse event that would prevent a prospective study participant from receiving the study treatment.
- Known untreated urethral strictural disease or bladder neck contracture or any other condition that may prevent catheterization with 21F catheter. Patients may undergo dilation or urethral incision before entering the study.
- Bladder diverticula with cumulative diameter > 1cm or tumor in a diverticulum.
- UTI at any time within 4 weeks before treatment start.
- Significant urinary incontinence (spontaneous, requiring use of pads).
- History of pelvic irradiation.
- Patients with implanted electronic devices (such as cardiac pacemakers) unless they receive permission from their treating physician (e.g., cardiologist) and are monitored by a treating physician during the treatment session.
- Participation in another study, unless discussed with and approved by the study manager.
About this study
Official title: A Multicenter, Single-Arm Study Evaluating the Efficacy of Synergo® Radiofrequency-Induced Thermochemotherapy Effect With Mitomycin C in Non-Muscle Invasive Bladder Cancer Patients With BCG-refractory CIS
This multicenter, prospective, single-arm, phase 3 study will assess the proportion of disease-free patients, starting from administration of the first study treatment to at least 12-months after the first treatment, and up to 2 years (the latter only in patients choosing to participate in longer-term disease-free-survival data collection).
Read the detailed description
The study will consist of three periods: 1) Screening; 2) Induction, and 3) Maintenance treatment and follow-up.
Screening period After signing informed consent, patients will be screened for study eligibility by assessment of inclusion and exclusion criteria. Screening procedures will include collection of demographic data, medical history, physical examination, vital signs, and laboratory evaluations.
Induction period Patients will receive 8 weekly treatments of RITE + MMC, using the Synergo® System. Each treatment lasts about 60 minutes and consists of two 30-minute cycles with 40 mg MMC/50 ml sterile water for injection each cycle. These 8 treatments will be followed by a pause (see Table 1), after which a follow-up cystoscopy (first follow-up control) will be conducted during Weeks 12-13 (from the first treatment).
Maintenance Treatment and Follow-up Period
During the maintenance period, patients will receive one Synergo® RITE + MMC treatment every 6 weeks. Each treatment lasts about 60 minutes and consists of two 30-minute cycles with 40 mg MMC/50 ml sterile water for injection each cycle. Maintenance treatments will be given until the end of 12 months after the patient's first induction treatment, unless the patient's participation in the study is terminated due to either:
- a lack of complete response (at 6 months) or worsening of disease (at 3 months; see first and second follow-up control below), or
- recurrence/progression Patients will be assessed by cystoscopy, urine cytology and, if required, subsequent biopsy or transurethral resection (TUR) of suspect areas every 3 months till the end of the study.
Two consecutive definite positive urine cytologies will be required to confirm persistent or recurrent disease if visual and biopsy are negative. In such cases, investigation of extravesical locations (CT-IVU, prostatic urethra biopsy) will be performed between the first and second urine cytology.
At the first follow-up control, i.e., 3 months after administration of the first study treatment, patients will undergo a cystoscopy evaluation.
Patients failing to achieve a disease-free state at the time of the first follow-up will continue in the study, unless a new occurrence of a T1 and/or high-grade lesion is found or any extra-bladder involvement is evident from pathological analysis.
At the second, i.e., 6-month, follow-up visit, patients will undergo biopsies of suspicious areas and random bladder biopsies of the trigone, bladder dome, right, left, anterior and posterior of the bladder wall. Upper tract washes will be performed in patients in whom urine cytology will be positive with no pathological evidence of NMIBC lesions in the bladder or the prostatic urethra. Patients failing to achieve a disease-free state at the time of the 6 month assessment and/or experiencing a new disease occurrence, demonstrated by cystoscopy and biopsy, and/or in whom extra-bladder involvement is suggested by a positive upper tract washes result will be removed from the study.
Upper tract imaging (CT-IVU imaging is recommended, IVU if CT not available) will be performed at 12 months from the first study treatment.
Extended treatment and follow-up period For longer-term disease-free-survival data collection purposes, patients free of tumor at the end of the study will be offered to continue receiving one Synergo® RITE + MMC treatment every 8 weeks. Each such treatment will last about 60 minutes and will consist of two 30-minute cycles with 40 mg MMC/50 ml sterile water for injection, each cycle. These treatments will be given until the end of 24 months after the patient's first induction treatment. See table 2 for details on the extended treatment and follow-up.
- Conditions
- Bladder Cancer
- Being tested
- Synergo® RITE + MMC
- Keywords
- NMIBC, Non-Muscle-Invasive Bladder Cancer, Nonmuscle Invasive Bladder Cancer, BCG refractory, BCG failure, Carcinoma in situ, CIS
- Medical subject headings
- Urinary Bladder Neoplasms, Non-Muscle Invasive Bladder Neoplasms, Carcinoma in Situ
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Synergo® RITE + MMCDevice
Synergo® system delivers homogenous microwave hyperthermia to the bladder wall in combination with bladder instillation of cold chemotherapeutic agent - Mitomycin C (MMC).The energy-delivering unit and the intravesical irrigation system are computer-controlled, The irrigation system consists of a disposable tubing line and catheter set. The catheter is a triple-lumen, silicone, transurethral Foley-type catheter.
MMC is constituted as a powder (40 mg) dissolved in 50 ml sterile water for injection.
| Study group | Role | What they receive |
|---|---|---|
| Synergo® RITE + MMC | Experimental | Induction
Patients will receive 8 weekly treatments of Synergo® RITE + MMC, using the Synergo® System. Each treatment lasts about 60 minutes and consists of two 30-minute cycles with 40 mg MMC/50 ml sterile water for injection each cycle. These 8 treatments will be followed by a pause (see Table 1), after which a follow-up cystoscopy (first follow-up control) will be conducted during Weeks 12-13 (from the first treatment).
Maintenance
Patients will receive one Synergo® RITE + MMC treatment every 6 weeks. Each treatment lasts about 60 minutes and consists of two 30-minute cycles with 40 mg MMC/50 ml sterile water for injection each cycle. Maintenance treatments will be given until the end of 12 months after the patient's first induction treatment. Receives: Device: Synergo® RITE + MMC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence-free survival
The study will be deemed successful if the recurrence-free survival probability after 12 months is at least 30%.
Measured: 12 months
Secondary outcomes (3)
Complete Response Rate (CRR)
A satisfactory outcome will be if the CRR at 6 months is at least 40%.
Measured: 6 months after first treatment
Rate of serious adverse events
Measured: 12 months
Proportion of patients who discontinue treatment for safety reasons.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2015 (estimated)
- Study startSep 2016
- Primary completionJan 2019 (estimated)
- Study completionJan 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical Enterprises Europe B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Igal Ruvinsky, PhD, Study director, Medical EnterprisesShariat Shahrokh, Prof. med, Principal investigator, Medical University Vienna, General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02471495
- Sponsor's protocol ID
- RITE-2
- Status last verified
- May 2018
- First submitted
- 11 Jun 2015
- Last updated
- 7 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Single-Arm Study Evaluating the Efficacy of Synergo® Radiofrequency-Induced Thermochemotherapy Effect With Mitomycin C in Non-Muscle Invasive Bladder Cancer Patients With BCG-refractory CIS
- ClinicalTrials.gov ID
- NCT02471495
- Acronym / sponsor ID
- RITE-2
- Conditions
- Bladder Cancer
- Keywords
- NMIBC, Non-Muscle-Invasive Bladder Cancer, Nonmuscle Invasive Bladder Cancer, BCG refractory, BCG failure, Carcinoma in situ, CIS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Medical Enterprises Europe B.V.Industry (pharma, biotech, devices)
- Study start
- Sep 2016
- Primary completion
- Jan 2019 (estimated)
- Study completion
- Jan 2020 (estimated)
- First posted
- 15 Jun 2015 (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.
This multicenter, prospective, single-arm, phase 3 study will assess the proportion of disease-free patients, starting from administration of the first study treatment to at least 12-months after the first treatment, and up to 2 years (the latter only in patients choosing to participate in longer-term disease-free-survival data collection).
Detailed description
The study will consist of three periods: 1) Screening; 2) Induction, and 3) Maintenance treatment and follow-up.
Screening period After signing informed consent, patients will be screened for study eligibility by assessment of inclusion and exclusion criteria. Screening procedures will include collection of demographic data, medical history, physical examination, vital signs, and laboratory evaluations.
Induction period Patients will receive 8 weekly treatments of RITE + MMC, using the Synergo® System. Each treatment lasts about 60 minutes and consists of two 30-minute cycles with 40 mg MMC/50 ml sterile water for injection each cycle. These 8 treatments will be followed by a pause (see Table 1), after which a follow-up cystoscopy (first follow-up control) will be conducted during Weeks 12-13 (from the first treatment).
Maintenance Treatment and Follow-up Period
During the maintenance period, patients will receive one Synergo® RITE + MMC treatment every 6 weeks. Each treatment lasts about 60 minutes and consists of two 30-minute cycles with 40 mg MMC/50 ml sterile water for injection each cycle. Maintenance treatments will be given until the end of 12 months after the patient's first induction treatment, unless the patient's participation in the study is terminated due to either:
- a lack of complete response (at 6 months) or worsening of disease (at 3 months; see first and second follow-up control below), or
- recurrence/progression Patients will be assessed by cystoscopy, urine cytology and, if required, subsequent biopsy or transurethral resection (TUR) of suspect areas every 3 months till the end of the study.
Two consecutive definite positive urine cytologies will be required to confirm persistent or recurrent disease if visual and biopsy are negative. In such cases, investigation of extravesical locations (CT-IVU, prostatic urethra biopsy) will be performed between the first and second urine cytology.
At the first follow-up control, i.e., 3 months after administration of the first study treatment, patients will undergo a cystoscopy evaluation.
Patients failing to achieve a disease-free state at the time of the first follow-up will continue in the study, unless a new occurrence of a T1 and/or high-grade lesion is found or any extra-bladder involvement is evident from pathological analysis.
At the second, i.e., 6-month, follow-up visit, patients will undergo biopsies of suspicious areas and random bladder biopsies of the trigone, bladder dome, right, left, anterior and posterior of the bladder wall. Upper tract washes will be performed in patients in whom urine cytology will be positive with no pathological evidence of NMIBC lesions in the bladder or the prostatic urethra. Patients failing to achieve a disease-free state at the time of the 6 month assessment and/or experiencing a new disease occurrence, demonstrated by cystoscopy and biopsy, and/or in whom extra-bladder involvement is suggested by a positive upper tract washes result will be removed from the study.
Upper tract imaging (CT-IVU imaging is recommended, IVU if CT not available) will be performed at 12 months from the first study treatment.
Extended treatment and follow-up period For longer-term disease-free-survival data collection purposes, patients free of tumor at the end of the study will be offered to continue receiving one Synergo® RITE + MMC treatment every 8 weeks. Each such treatment will last about 60 minutes and will consist of two 30-minute cycles with 40 mg MMC/50 ml sterile water for injection, each cycle. These treatments will be given until the end of 24 months after the patient's first induction treatment. See table 2 for details on the extended treatment and follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Synergo® RITE + MMC | Experimental | Device: Synergo® RITE + MMCInduction Patients will receive 8 weekly treatments of Synergo® RITE + MMC, using the Synergo® System. Each treatment lasts about 60 minutes and consists of two 30-minute cycles with 40 mg MMC/50 ml sterile water for injection each cycle. These 8 treatments will be followed by a pause (see Table 1), after which a follow-up cystoscopy (first follow-up control) will be conducted during Weeks 12-13 (from the first treatment). Maintenance Patients will receive one Synergo® RITE + MMC treatment every 6 weeks. Each treatment lasts about 60 minutes and consists of two 30-minute cycles with 40 mg MMC/50 ml sterile water for injection each cycle. Maintenance treatments will be given until the end of 12 months after the patient's first induction treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (32 listed)
- Patients with CIS, with or without coexisting papillary NMIBC, who either:
- All clinical, intra-operative and pathological items for the EAU risk stratification must be documented including a bladder map.
- Patients with papillary disease must have undergone a repeat TUR:
- CT-IVU or IVU confirmation of absence of tumor(s) in the upper tract, kidney and ureters performed within 6 months before the treatment initiation in selected cases as recommended in latest EAU guidelines published prior to screening. If IVU protocol not available or contrast allergy/poor renal function preclude such imaging, then non-contrast CT or MRI of the abdomen/pelvis within the same timeframe will suffice.
- Visual inspection to exclude urothelial carcinoma (UC) in the urethra during cystoscopy.
Key exclusion criteria (22 listed)
- Non-UC tumor of the urinary tract.
- Upper tract and intramural tumors (e.g., in ostium).
- Positive selective cytology from the upper tract.
- History of stage > T1 UC.
- Papillary tumor in repeat TUR in patients diagnosed with HG > 3cm and/or T1 in the initial TUR.
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® RITE + MMCSynergo® system delivers homogenous microwave hyperthermia to the bladder wall in combination with bladder instillation of cold chemotherapeutic agent - Mitomycin C (MMC).The energy-delivering unit and the intravesical irrigation system are computer-controlled, The irrigation system consists of a disposable tubing line and catheter set. The catheter is a triple-lumen, silicone, transurethral Foley-type catheter. MMC is constituted as a powder (40 mg) dissolved in 50 ml sterile water for injection. | Device | Synergo® RITE + MMC |
Primary outcome
Recurrence-free survival
Time frame: 12 months
The study will be deemed successful if the recurrence-free survival probability after 12 months is at least 30%.
3 secondary outcomes
Complete Response Rate (CRR)
Time frame: 6 months after first treatment
Rate of serious adverse events
Time frame: 12 months
Proportion of patients who discontinue treatment for safety reasons.
Time frame: 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2018.
- Individual participant dataSharing planned: No
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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.
Igal Ruvinsky, PhD study director
Medical Enterprises
Shariat Shahrokh, Prof. med principal investigator
Medical University Vienna, General Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Synergo® RITE + MMC in people with Bladder Cancer, run by Medical Enterprises Europe B.V..
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 32 inclusion and 22 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: withdrawn, as of the sponsor's last update on 7 May 2018. Status can change between updates, so confirm with the study contact before making plans.
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 withdrawn before enrolling participants, so there are no results.
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: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 May 2018.