Clinical trial NCT00384891: Hyperthermia Treatment in Conjunction With Mitomycin C Versus Bacillus Calmette-Guérin Immunotherapy (BCG) for Superficial Bladder Cancer
Official title: A Randomized Controlled Study Comparing Adjuvant Hyperthermia Treatment in Conjunction With Mitomycin C Versus BCG Immunotherapy (BCG) Adjuvant Treatment in Patients With Superficial Transitional Cell Carcinoma of the Bladder (STCCB)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Urinary Bladder Diseases
Urinary Bladder Neoplasms
Urinary Bladder Cancer
Malignant Tumor of Urinary Bladder
Urologic Diseases
Urologic Neoplasms
Neoplasms
Neoplasms by Site
Keywords: Superficial urothelial cell carcinoma of bladder
NMIBC
Non Muscle Invasive Bladder Cancer
Hyperthermia
Bladder instillation
Mitomycin C
RITE
SHTC
Intravesical
Lead sponsor: Medical Enterprises Europe B.V.
Sponsor class: INDUSTRY
First posted: 2006-10-06
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is designed to compare the efficacy and safety of 2 treatment types for the prevention of tumor recurrence of superficial bladder cancer:

1. A combination of bladder wall heating and local chemotherapy (Synergo)
2. Bacillus Calmette-Guérin (BCG)

Detailed description: The study is a randomized controlled study, designed to test the efficacy and safety of a new treatment modality for the prevention of tumor recurrence in superficial bladder cancer.

Patients must have their tumors surgically resected prior to study enrollment, and undergo a series of tests to prove their bladder is now free of tumor. Eligible patients will be randomly assigned to one of 2 treatment arms:

1. A combination of bladder wall heating and local chemotherapy (Synergo)
2. Bacillus Calmette-Guérin (BCG)

Patients will be treated during the first year of the study, and will be followed up for a total of 2 years. The follow up will include a visual evaluation of the patient's bladder by cystoscopy, a cytological examination of the urine (to look for malignant cells) and other additional exams. The patients' general welfare will be monitored through out the study.

The aim of this study is to compare the efficacy and safety of the novel treatment (Synergo) to that of the well-known BCG

Eligibility criteria: Inclusion Criteria:

* Superficial TCC: Any G3 or any T1 and/or CIS
* Multifocal (\>1) Ta lesions
* Multiple recurrences (\>2) of Ta lesions in the last 24 months
* Complete tumor eradication must be confirmed
* WHO performance status 0-2 (Appendix V)
* Life expectancy of more than 24 months
* Patients willing to sign informed consent

Exclusion Criteria:

* Bladder tumors other than TCC
* Coexistence of another primary malignant tumor other than BCC of the skin
* TCC of the bladder involving the urethra or upper urinary tract
* Previous history of TCC stage T2 or higher
* Clinical presence or previous history of regional spreading or distant metastases
* Intravesical MMC treatments during the last 12 months
* Previous intravesical BCG therapy (Any intravesical BCG therapy in the last 24 months, or More than 6 BCG intravesical instillations in the last 48 months.
* Previous pelvic radiotherapy or systemic chemotherapy
* Partial cystectomy
* Diverticle of bladder larger than 1cm in diameter
* Residual urine \> 100cc measured by uroflowmetry
* Bladder volume \< 150cc measured by ultrasound
* Urinary incontinence (more than one wet pad a day)
* Urethral stricture impeding 20F catheterization
* Urethral bleeding or persistent hematuria
* Active intractable or uncontrollable UTI
* Active tuberculosis or BCG infection
* Patients who experienced BCG life threatening sepsis
* Known allergy to MMC or BCG
* Known impaired immune response, positive HIV serology, patients receiving systemic steroids or immunosuppressive therapy
* Hematological disorders; leukocytes \< 3500, platelets \< 100,000
* Kidney or liver function disorders (more than 1.5 times upper normal limit)
* Pregnant or lactating women
* Patients who cannot be followed up properly or are unable to collaborate

Primary outcomes:
measure: Recurrence free survival
timeFrame: 2 years
Secondary outcomes:
measure: Proportion of complete response in CIS patients
timeFrame: 3 months
measure: Progression rate (to disease stage>T1) and/or metastatic disease
timeFrame: 2 years
measure: Local and systemic side effects, both subjective and objective
timeFrame: 2 years
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: University Hospital - AKH Vienna
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Holon
country: Israel
facility: Wolfson Hospital
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Genova
country: Italy
facility: Galliera Hospital
city: Milan
country: Italy
facility: Istituto Europeo del Oncologia
city: Milan
country: Italy
facility: San Raffaele Hospital (HSR)
city: Nijmegen
country: Netherlands
facility: Department of Urology, Radboud University Hospital
Study officials:
affiliation: Department of Urology, Radboud University Hospital, Nijmegen, The Netherlands
name: Alfred A Witjes, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Arends TJ, Nativ O, Maffezzini M, de Cobelli O, Canepa G, Verweij F, Moskovitz B, van der Heijden AG, Witjes JA. Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guerin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non-Muscle-invasive Bladder Cancer. Eur Urol. 2016 Jun;69(6):1046-52. doi: 10.1016/j.eururo.2016.01.006. Epub 2016 Jan 20.