Clinical trial NCT00330707: Combined Use of BCG and Interferon Alpha in Bladder Cancer
Official title: A Multi-centre Randomised Controlled Double-blinded Trial of BCG and Interferon Alpha in High Risk Superficial Bladder Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Carcinoma of Urinary Bladder, Superficial
Keywords: bladder cancer
BCG
interferon alpha
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
Collaborators: name: National Medical Research Council (NMRC), Singapore
First posted: 2006-05-29
Enrollment: 140
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: To compare the toxicity and efficacy of the combination of BCG and interferon alpha to standard dose and low dose BCG alone in high risk superficial bladder cancer

Detailed description: 140 eligible patients with high risk superifical bladder cancer would be randomised to receive standard dose BCG, low dose BCG or the combination of low dose BCG and interferon alpha in a schedule of "6+3" weekly intravesical instillations. Patients would be closely monitored with cystoscopy and urine cytology and intravenous urograms when indicated. Pre-and post-instillation urine samples would be collected for cytokine analysis.

Eligibility criteria: Inclusion Criteria:

(1) Patients must have completely resected, histologically?proven urothelial carcinoma of the urinary bladder, stage Ta or Tl 1 ? 16 weeks prior to registration, and/or carcinoma-in-situ on bladder biopsy. Central pathology review was mandatory. (2) Patients with Stage Ta urothelial carcinoma must be judged to be at increased risk of tumor recurrence by virtue of any one of the following: (a) Tumor recurrence during the 56 weeks prior to registration, (b) Two or more initial tumors within 28 weeks, (c) Grade III urothelial carcinoma during the 16 weeks prior to registration, (d) Dysplasia or carcinoma-in-situ on random biopsy or (e) Positive urinary cytology post tumor resection. "Suspicious" or "suggestive" cytology is insufficient for this criterion. (3) Patients who have received prior intravesical therapy other than BCG were eligible provided they had not undergone a course of any other intravesical agent within two months prior to entry. (4) There was no age restriction; however, all patients registered had to be willing to be available for 5?year follow up and to have a life expectancy of at least two years. (5) Patients had a Karnofsky score \>50. (6) Women of child?bearing age were using effective contraceptive methods. (7) Patients agreed not to take vitamin supplements (except for those prescribed in the study) for the duration of the trial. (8) Pretreatment laboratory tests and radiological examinations must have been obtained during the 16 weeks prior to patient registration. (9) All patients had to be informed of the investigational nature of this study, and had to sign a written informed consent in accordance with institutional guidelines.

Exclusion Criteria:

* (1) Patients with medical illness or mental status, which would preclude cooperation with the study. (2) Patients who were immunodeficient, or had received immunosuppressive radiation therapy or chemotherapy. (3) Patients with urothelial carcinoma of stage T2 or higher. (4) Patients who had evidence of urothelial carcinoma of the upper urinary tract at the time of recruitment. (5) Patients who had received radiation therapy for bladder cancer within one year prior to registration. (6) Patients who had been previously treated with intravesical BCG. (7) Patients with active tuberculosis.

Primary outcomes:
measure: local toxicity
measure: systemic toxicity
measure: recurrence rate
measure: progression rate
measure: disease-specific mortality
Secondary outcomes:
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
Study officials:
affiliation: National University of Singapore
name: Kesavan Esuvaranathan, FRCSEd MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chiong E, Kesavan A, Mahendran R, Chan YH, Sng JH, Lim YK, Kamaraj R, Tan TM, Esuvaranathan K. NRAMP1 and hGPX1 gene polymorphism and response to bacillus Calmette-Guerin therapy for bladder cancer. Eur Urol. 2011 Mar;59(3):430-7. doi: 10.1016/j.eururo.2010.11.031. Epub 2010 Dec 1.