Clinical trial NCT06768346: Hyperthermic Intra-Vesical Chemotherapy
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bladder Cancer
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
First posted: 2025-01-10
Enrollment: 259
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

1. 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
2. Age ≥ 18 yrs
3. WHO performance status 0, 1, 2, 3
4. Pre-treatment haematology and biochemistry values within acceptable limits:

   * 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
5. Negative pregnancy test for women of child-bearing potential.
6. Available for long-term follow-up.
7. 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.
8. Written informed consent.

Exclusion Criteria:

1. Grade 3 TCC
2. Carcinoma in situ.
3. New solitary Ta G1 (small)
4. New solitary Ta G2 (small)
5. Previous intravesical chemotherapy in the past 6 months, other than single instillation post-TUR.
6. Bladder capacity \<200cc.
7. UCC involving the prostatic urethra or upper urinary tract.
8. \> or =T2 UCC
9. Known allergy to mitomycin
10. Pregnant or lactating women or women of childbearing potential unwilling or unable to use adequate non-hormonal contraception.
11. 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.
12. Concurrent chemotherapy.

Primary outcomes:
measure: To determine if HIVEC increases disease-free survival at 24 months compared to the comparator arm of MM alone.
timeFrame: After the last patient has completed 24 months follow-up
Secondary outcomes:
measure: To determine if HIVEC reduces the risk of recurrence at 3 months compared to the control arm, for patients with intermediate risk disease.
timeFrame: At the end of study - After all patients have been followed-up for at least 2 years
measure: Progression Free Survival
timeFrame: At the end of study - After all patients have been followed-up for at least 2 years
measure: Recurrence-free survival.
timeFrame: At the end of study - After all patients have been followed-up for at least 2 years
measure: To determine if Heated Mytomycin reduces the risk of progression to invasive disease compared to the control arm.
timeFrame: After all patients have been followed-up for at least 2 years
measure: To compare overall and disease-specific survival between the Heated Mytomycin and the control arm.
timeFrame: At the end of study - After all patients have been followed-up for at least 2 years
measure: To define the safety and tolerability of Heated Mytomycin in this patient population.
timeFrame: At the end of study - After all patients have been followed-up for at least 2 years
measure: To compare QOL between the Heated Mytomycin and the control arms.
timeFrame: After all patients have been followed-up for at least 2 years
Other outcomes:
Locations:
city: Bath
country: United Kingdom
facility: Royal United Hospitals Bath NHS Foundation Trust
city: Edinburgh
country: United Kingdom
facility: Western General Hospital, Edinburgh
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital NHS Foudation Trust
city: Liverpool
country: United Kingdom
facility: The Clatterbridge Cancer Centre
city: London
country: United Kingdom
facility: Barnet Hospital
city: London
country: United Kingdom
facility: St George's University Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospital, London.
city: Manchester
country: United Kingdom
facility: University Hospital of South Manchester
city: Middlesborough
country: United Kingdom
facility: South Tees NHS Trust - James Cook University Hospital
city: Norwich
country: United Kingdom
facility: Norfolk & Norwich University Hospitals NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Portsmouth
country: United Kingdom
facility: Portsmouth Hospitals NHS Trust - Queen Alexandra Hospital
city: Redhill
country: United Kingdom
facility: East Surrey Hospital
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
affiliation: Queen Mary University of London
name: Dr John Kelly
role: PRINCIPAL_INVESTIGATOR
References: