A Phase II, Open Label, Multicenter Randomised Controlled Trial Comparing Hyperthermia Plus Mitomycin To Mitomycin Alone, In Patients with Intermediate Risk Non-Muscle Invasive Bladder Cancer

ISRCTN	ISRCTN23639415
DOI	https://doi.org/10.1186/ISRCTN23639415
Secondary identifying numbers	15853

Submission date: 17/04/2014
Registration date: 17/04/2014
Last edited: 08/03/2024

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

http://www.cancerresearchuk.org/about-cancer/trials/a-trial-chemotherapy-hyperthermia-early-bladder-cancer-hivec-ii

Contact information

Mr Shriram Velamuri
Scientific

Centre for Experimental Cancer Medicine, LG floor
Old Anatomy Building Charterhouse Square
London
EC1M 6BQ
United Kingdom

Email	s.velamuri@qmul.ac.uk

Study information

Study design	Randomised; Interventional; Design type: Treatment
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	GP practice
Study type	Treatment
Scientific title	A Phase II, Open Label, Multicenter Randomised Controlled Trial Comparing Hyperthermia Plus Mitomycin To Mitomycin Alone, In Patients with Intermediate Risk Non-Muscle Invasive Bladder Cancer
Study acronym	Hyperthermia for Intermediate risk bladder cancer (HIVEC-II)
Study hypothesis	In the UK, 11000 new cases of bladder cancer are diagnosed per year; it is the fourth commonest non dermatological malignancy in males and tenth most common in females. Non-Muscle invasive bladder cancer comprise (70-80%) of Transitional cell carcinoma at presentation and is defined as a disease confined to the mucosa (TCC) or lamina propria (T1) and carinoma in situ (CIS). With in three years 15-70% of tumors recur following Trans urethral resection and 6-45% can complete despite adjuvant therapy. Patients at intermediate risk for recurrence following TUR receive a single instillation of mitomycin followed by additional adjuvant therapy. Adjuvant MM reduces the recurrence rate, consists of six weekly consecutive weekly intravesical instillation. Intravesical chemoprophylaxis following TUR results in a reduced risk of recurrence compared to TUR alone. Recurrence rates following adjuvant chemotherapy are reduced by 25-50%within two years. 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. Hypethermia in combination with chemotherapy has been widely used in cancer treatment. The effects of hyperthermia alter cell physiology, growth and survival and in combination with chemotherapy,hyperthermia increases the drug uptake, increases the drug reaction and enhances the inhibition of DNA repair in the damaged neoplastic cells. The aim of the trial is to determine whether HIVEC is an effective therapy for patients with intermediate risk NMIBC. The trial include patients who have new disease and disease recurrence. The primary objective of the study is to compare the treatments in terms of disease-free survival at 24months in all patients.
Ethics approval(s)	13/LO/1434; First MREC approval date 07/11/2013
Condition	Topic: Cancer; Subtopic: Bladder Cancer; Disease: Bladder (advanced), Bladder (superficial)
Intervention	Mitomycin, Mitomycin will be given in either normal and hyperthermic state.; Follow Up Length: 24 month(s); Study Entry : Single Randomisation only
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase II
Drug / device / biological / vaccine name(s)	Mitomycin
Primary outcome measure	Primary Objective; Timepoint(s): To determine if HIVEC increases disease-free survival at 24 months compared to the comparator arm of
Secondary outcome measures	Not provided at time of registration
Overall study start date	19/03/2014
Overall study end date	01/10/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	Planned Sample Size: 191; UK Sample Size: 191
Total final enrolment	259
Participant inclusion criteria	1. New or Recurrence of intermediate risk NMIBC following TURBT defined as; 1.1.Grade 2 or grade 1 stage Ta or T1 disease. 1.2. Any grade G2 or G1 recurrent bladder cancer other than low-risk and muscle-invasive disease 2. Age = 18 years 3. WHO performance status 0, 1, 2, 3 4. Normal kidneys and ureters on imaging study within the past 12 months* 5. Pre-treatment haematology and biochemistry values within acceptable limits: 5.1. Haemoglobin (greater than or equal to)10 g/dl 5.2. Neutrophil count (Greater than or equal to)1.5 x 10^9/l 5.3. Platelets (Greater than or equal to) 100 x 10^9/l 5.4. WBC (Greater than or equal to) 3.0 X 10^9/l or ANC greater than or equal to 1.5 X 10^9/l 5.5. Serum creatinine < 1.5 X UNL 6. Negative pregnancy test for women of childbearing potential. 7. Available for longterm followup. 8. 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. 9. Written informed consent. T1 disease must have evidence of muscle in specimen. If muscularis propria is not present, a reresection should be performed (accordance with National best practice policy) *Imaging of upper tracts by CT or US scan is routinely performed in some centres and is recommended as good practice in this study Target Gender: Male & Female ; Lower Age Limit 18 years
Participant exclusion criteria	1. Grade 3 TCC 2. Carcinoma in situ 3. New solitary Ta G1 (Small)<3cm 4. New solitary Ta G2 (Small)<3cm 5. Previous intravesical chemotherapy in the past 6 months, other than single instillation postTUR. 6. History of limited vesicle capacity (<200cc) 7. UCC involving the prostatic urethra or upper urinary tract. 8. Greater than or equal to T2 UCC 9. Known allergy to mitomycin 10. Pregnant or lactating women or women of childbearing potential unwilling or unable to use adequate nonhormonal 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 less than 5yrs life expectancy. 12. Concurrent chemotherapy.
Recruitment start date	19/03/2014
Recruitment end date	01/10/2017

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Centre for Experimental Cancer Medicine, LG floor

London
EC1M 6BQ
United Kingdom

Sponsor information

Queen Mary University of London (UK)
University/education

Suite 3.1 Dominion House
59 Batholomew Close
London
SW18 1JG
England
United Kingdom

"ROR"	https://ror.org/026zzn846

Funders

Funder type

Industry

Combat Medical Ltd.

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	20/08/2022	24/08/2022	Yes	No
HRA research summary		28/06/2023	No	No
Plain English results		08/03/2024	No	Yes

Editorial Notes

08/03/2024: Cancer Research UK plain English results link added.
24/08/2022: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.