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Completed

NCT Number: NCT06768346

Hyperthermic Intra-Vesical Chemotherapy

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.

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Key information

Conditions

Bladder Cancer Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Male Urogenital Diseases Neoplasms Neoplasms by Site Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Royal United Hospitals Bath NHS Foundation Trust, Bath, United Kingdom

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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:
  • 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.

Exclusion criteria

  • 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.
  • 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.

Treatment and study plan

Hyperthermia will be delivered in combination with each instillation using the Combat BRS system

Device

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.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

    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.

  2. Progression Free Survival

    Time frame: At the end of study - After all patients have been followed-up for at least 2 years

    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

  3. Recurrence-free survival.

    Time frame: At the end of study - After all patients have been followed-up for at least 2 years

    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.

  4. 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

    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.

  5. 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

    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.

  6. 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

    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

  7. 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

    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.

Sponsors and collaborators

Lead sponsor

Queen Mary University of London

Other

Registry information

Official study 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

Acronym: HIVECII

Important dates

Study start
2014
Primary completion
2020
Study completion
2020
First posted
Jan 10, 2025
Registry last updated
Jan 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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