Bladder CancerHIVECIINCT06768346
Hyperthermic Intra-Vesical Chemotherapy
A study testing Hyperthermia will be delivered in combination with each instillation using the Combat BRS system in people with Bladder Cancer, run by Queen Mary University of London at 14 sites in United Kingdom.
Trial summary
The purpose of the HIVEC II trial is to find out if the combination of the new technology called hyperthermia (the use of heat) and a drug called mitomycin is more effective than mitomycin alone which is the standard treatment for bladder cancer in reducing the chances of bladder cancer returning. 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?
- Hyperthermia will be delivered in combination with each instillation using the Combat BRS system
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 259 participants
- Where
- 14 sitesUnited Kingdom
- Study dates
- 8 May 2014to 27 May 2020
- Phase
- Interventional
- 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
- New or Recurrence of intermediate risk NMIBC following TURBT defined as;
- Grade 2 or grade 1 stage Ta or T1 disease*.
- Any grade G2 or G1 other than Low risk
- Age ≥ 18 yrs
- WHO performance status 0, 1, 2, 3
- Pre-treatment haematology and biochemistry values within acceptable limits:
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- Haemoglobin > or =10 g/dL
- Neutrophil count > or =1.5 x 109/L
- Platelets > or = 100 x 109/L
- WBC > or = 3.0 x 109/L or ANC > or = 1.5 x 109/L
- Serum creatinine < 1.5 x UNL
- Negative pregnancy test for women of child-bearing potential.
- Available for long-term follow-up.
- Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 6 weeks after treatment discontinuation.
- Written informed consent.
Who cannot join
- Grade 3 TCC
- Carcinoma in situ.
- New solitary Ta G1 (small)
- New solitary Ta G2 (small)
- Previous intravesical chemotherapy in the past 6 months, other than single instillation post-TUR.
- Bladder capacity <200cc.
Show all 12Show fewer
- UCC involving the prostatic urethra or upper urinary tract.
- > or =T2 UCC
- Known allergy to mitomycin
- Pregnant or lactating women or women of childbearing potential unwilling or unable to use adequate non-hormonal contraception.
- Other malignancy within the past five years, except: non-melanomatous skin cancer cured by excision, adequately treated carcinoma in situ of the cervix or DCIS/LCIS of the breast or prostate cancer with more than 5yrs life expectancy or any non lifethreatening tumours that have been curatively treated.
- Concurrent chemotherapy.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United Kingdom14 sites
Royal United Hospitals Bath NHS Foundation Trust
Bath
Western General Hospital, Edinburgh
Edinburgh
Royal Surrey County Hospital NHS Foudation Trust
Guildford, GU2 7XX
The Clatterbridge Cancer Centre
Liverpool
Barnet Hospital
London
St George's University Hospitals NHS Foundation Trust
London
University College London Hospital, London.
London
University Hospital of South Manchester
Manchester, M239QZ
South Tees NHS Trust - James Cook University Hospital
Middlesbrough
Norfolk & Norwich University Hospitals NHS Foundation Trust
Norwich
Derriford Hospital
Plymouth
Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital
Portsmouth
East Surrey Hospital
Redhill
New Cross Hospital
Wolverhampton
About this study
Official title: A Phase II, Open Label, Multicentre, Randomised Controlled Trial Comparing Hyperthermia Plus Mitomycin To Mitomycin Alone In Patients With Intermediate Risk Non-Muscle Invasive Bladder Cancer
The purpose of the HIVEC II trial is to find out if the combination of the new technology called hyperthermia (the use of heat) and a drug called mitomycin is more effective than mitomycin alone which is the standard treatment for bladder cancer in reducing the chances of bladder cancer returning.
Read the detailed description
The concept of hyperthermia plus MM has been demonstrated and a phase II randomized controlled trial of ablative HM versus MM using an alternative device (Synergo) has reported tumor ablation complete response (CR) rates in 66 % of tumors treated with hyperthermia plus mitomycin compared to 22% CR for MM mono-therapy.
Registered patients will be randomised to receive either Hyperthermia and Mitomycin or Mitomycin alone. Following treatment, patients will be followed up by surveillance cystoscopy for 24 months for disease recurrence. In the first year, the follow up visits will be every 3 months from the date of start of treatment and in the second year, the visits will be every 6 months.
The study also includes translational components to determine biomarkers of response to Heated Mitomycin. Urine samples will be collected prior to surveillance cystoscopies.
This study will address the problem of how to improve the disease free survival in patients with intermediate-risk NMIBC, the treatment must have acceptable side-effects, low toxicity, and show a significant benefit over MM alone.
- Conditions
- Bladder Cancer
- Being tested
- Hyperthermia will be delivered in combination with each instillation using the Combat BRS system
- 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.
Hyperthermia will be delivered in combination with each instillation using the Combat BRS systemDevice
The Combat BRS system is a temperature controlled fluid recirculation system for the delivery of hyperthermic intravesical chemotherapy. The chemotherapy fluid is circulated in a closed system and warmed by an external isolated dry system using a novel innovative laminated aluminium foil heat exchanger with a small priming volume.
| Study group | Role | What they receive |
|---|---|---|
| Mitomycin | No intervention | Patients will receive six consecutive weekly instillations of Mitomycin followed by surveillance |
| Hyperthermia+Mitomycin | Experimental | Patients will receive 6 weekly instillations of hyperthermia plus Mitomycin (HIVEC) using the COMBAT system, followed by surveillance cystoscopy. Receives: Device: Hyperthermia will be delivered in combination with each instillation using the Combat BRS system |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine if HIVEC increases disease-free survival at 24 months compared to the comparator arm of MM alone.
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 (known as Disease- free survival) will be measured.
of death from any cause.
Measured: After the last patient has completed 24 months follow-up
Secondary outcomes (7)
To determine if HIVEC reduces the risk of recurrence at 3 months compared to the control arm, for patients with intermediate risk disease.
The recurrence of tumor at 3 months will be calculated as a time to event outcome. recurrence of tumor at 3 months can predict subsequent recurrence and as a surrogate outcome will be monitored as a secondary measure.
Measured: At the end of study - After all patients have been followed-up for at least 2 years
Progression Free Survival
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
Measured: At the end of study - After all patients have been followed-up for at least 2 years
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 will not be included as an event, but rather considered a treatment failure and will be censored.
Measured: At the end of study - After all patients have been followed-up for at least 2 years
To determine if Heated Mytomycin reduces the risk of progression to invasive disease compared to the control arm.
Progression Free Survival will be compared between the 2 arms. Progression free survival is 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.
Measured: After all patients have been followed-up for at least 2 years
To compare overall and disease-specific survival between the Heated Mytomycin and the control arm.
Overall and Disease specific survival will be measured in terms of time interval. 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. 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.
Measured: At the end of study - After all patients have been followed-up for at least 2 years
To define the safety and tolerability of Heated Mytomycin in this patient population.
Safety and Tolerability will be reported through the number of adverse events. This will include assessment of frequency, severity and nature of adverse events and the treatment received
Measured: At the end of study - After all patients have been followed-up for at least 2 years
To compare QOL between the Heated Mytomycin and the control arms.
Quality of life will be assessed at study entry and every three months using the questionnaires. The questionnaires collects information about side effects and symptoms as well as measures of function and overall well being. For each part, a set scale will be used.
Measured: After all patients have been followed-up for at least 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2025
- Study start8 May 2014
- Primary completion27 May 2020
- Study completion27 May 2020
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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 259 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen Mary University of London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dr John Kelly, Principal investigator, Queen Mary University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06768346
- Sponsor's protocol ID
- BL-2013-04
- Acronym
- HIVECII
- Status last verified
- Jan 2025
- First submitted
- 25 Aug 2017
- Last updated
- 10 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open Label, Multicentre, Randomised Controlled Trial Comparing Hyperthermia Plus Mitomycin To Mitomycin Alone In Patients With Intermediate Risk Non-Muscle Invasive Bladder Cancer
- ClinicalTrials.gov ID
- NCT06768346
- Acronym / sponsor ID
- HIVECII / BL-2013-04
- Conditions
- Bladder Cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 259 participants (actual)
- Lead sponsor
- Queen Mary University of LondonUniversity, hospital or other
- Study start
- 8 May 2014 (actual)
- Primary completion
- 27 May 2020 (actual)
- Study completion
- 27 May 2020 (actual)
- First posted
- 10 Jan 2025 (actual)
- 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 purpose of the HIVEC II trial is to find out if the combination of the new technology called hyperthermia (the use of heat) and a drug called mitomycin is more effective than mitomycin alone which is the standard treatment for bladder cancer in reducing the chances of bladder cancer returning.
Detailed description
The concept of hyperthermia plus MM has been demonstrated and a phase II randomized controlled trial of ablative HM versus MM using an alternative device (Synergo) has reported tumor ablation complete response (CR) rates in 66 % of tumors treated with hyperthermia plus mitomycin compared to 22% CR for MM mono-therapy.
Registered patients will be randomised to receive either Hyperthermia and Mitomycin or Mitomycin alone. Following treatment, patients will be followed up by surveillance cystoscopy for 24 months for disease recurrence. In the first year, the follow up visits will be every 3 months from the date of start of treatment and in the second year, the visits will be every 6 months.
The study also includes translational components to determine biomarkers of response to Heated Mitomycin. Urine samples will be collected prior to surveillance cystoscopies.
This study will address the problem of how to improve the disease free survival in patients with intermediate-risk NMIBC, the treatment must have acceptable side-effects, low toxicity, and show a significant benefit over MM alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mitomycin | No intervention | –Patients will receive six consecutive weekly instillations of Mitomycin followed by surveillance |
| Hyperthermia+Mitomycin | Experimental | Device: Hyperthermia will be delivered in combination with each instillation using the Combat BRS systemPatients will receive 6 weekly instillations of hyperthermia plus Mitomycin (HIVEC) using the COMBAT system, followed by surveillance cystoscopy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- New or Recurrence of intermediate risk NMIBC following TURBT defined as;
- Age ≥ 18 yrs
- WHO performance status 0, 1, 2, 3
- Pre-treatment haematology and biochemistry values within acceptable limits:
- Negative pregnancy test for women of child-bearing potential.
Key exclusion criteria (12 listed)
- Grade 3 TCC
- Carcinoma in situ.
- New solitary Ta G1 (small)
- New solitary Ta G2 (small)
- Previous intravesical chemotherapy in the past 6 months, other than single instillation post-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 |
|---|---|---|
| Hyperthermia will be delivered in combination with each instillation using the Combat BRS systemThe Combat BRS system is a temperature controlled fluid recirculation system for the delivery of hyperthermic intravesical chemotherapy. The chemotherapy fluid is circulated in a closed system and warmed by an external isolated dry system using a novel innovative laminated aluminium foil heat exchanger with a small priming volume. | Device | Hyperthermia+Mitomycin |
Primary outcome
To determine if HIVEC increases disease-free survival at 24 months compared to the comparator arm of MM alone.
Time frame: After the last patient has completed 24 months follow-up
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 (known as Disease- free survival) will be measured. of death from any cause.
7 secondary outcomes
To determine if HIVEC reduces the risk of recurrence at 3 months compared to the control arm, for patients with intermediate risk disease.
Time frame: At the end of study - After all patients have been followed-up for at least 2 years
Progression Free Survival
Time frame: At the end of study - After all patients have been followed-up for at least 2 years
Recurrence-free survival.
Time frame: At the end of study - After all patients have been followed-up for at least 2 years
To determine if Heated Mytomycin reduces the risk of progression to invasive disease compared to the control arm.
Time frame: After all patients have been followed-up for at least 2 years
To compare overall and disease-specific survival between the Heated Mytomycin and the control arm.
Time frame: At the end of study - After all patients have been followed-up for at least 2 years
To define the safety and tolerability of Heated Mytomycin in this patient population.
Time frame: At the end of study - After all patients have been followed-up for at least 2 years
To compare QOL between the Heated Mytomycin and the control arms.
Time frame: After all patients have been followed-up for at least 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2025.
- Related InfoLink provided by the sponsor.
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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.
Dr John Kelly principal investigator
Queen Mary University of London
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Hyperthermia will be delivered in combination with each instillation using the Combat BRS system in people with Bladder Cancer, run by Queen Mary University of London at 14 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?
The sponsor lists 15 inclusion and 12 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: finished, as of the sponsor's last update on 10 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine if HIVEC increases disease-free survival at 24 months compared to the comparator arm of MM alone. (time frame: After the last patient has completed 24 months follow-up). 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 10 Jan 2025.