Mycobacterial Cell Wall-DNA Complex in Treatment of BCG-refractory Patients With Non-muscle Invasive Bladder Cancer
- Conditions
- Bladder Neoplasms
- Interventions
- Drug: Mycobacterial cell wall-DNA complex
- Registration Number
- NCT00406068
- Lead Sponsor
- Bioniche Life Sciences Inc.
- Brief Summary
The purpose of this study is to determine the efficacy and safety of intravesical Mycobacterial Cell Wall-DNA Complex (MCC) in patients with non-muscle invasive transitional cell carcinoma (papillary tumors and/or carcinoma in situ) of the urinary bladder at high risk of progression who are refractory to therapy with bacillus Calmette-Guerin (BCG).
- Detailed Description
The study will be divided into 3 phases: Induction, Maintenance, and Follow-up.
The Induction Phase will cover a period of 6 weeks. During this time, patients will receive 6 weekly intravesical instillations of 8 mg MCC. The patients will be evaluated at month 3, at which time the patients will enter the Maintenance Phase. The Maintenance Phase will last from month 3 to month 24, and during this time, patients will receive weekly MCC instillations for three weeks at months 3, 6, 12, 18, and 24 and evaluations will be performed at months 3, 6, 9, 12, 15, 18, 21 and 24.
At month 3, the patient will be evaluated to assure that the disease is not progressing. Cytology, cystoscopy and biopsies will be performed to obtain adequate staging (if residual tumor persists). If the patient is disease-free, maintenance therapy will be initiated. Patients with non-muscle invasive tumors at month 3 will, at the discretion of the investigator, receive either a second 6-week induction course or a 3-week maintenance course. Patients who show progression to muscle invasive disease will be referred to other treatments.
At month 6 and thereafter at each evaluation visit, patients will be evaluated and managed according to the following results:
* Patients who are disease-free will continue on maintenance treatment.
* Patients who are not disease-free (evidence of papillary lesions, CIS or muscle invasive disease) will be withdrawn from further study treatment and will be referred to other therapies at the discretion of the investigator.
The final 36 months of the study is the Follow-up Phase. Evaluations will be performed at months 30, 36, 42, 48, 54 and 60.
Efficacy evaluations will include standard cystoscopy, biopsies and urine cytology. During the Maintenance Phase, standard cystoscopies will be performed at months 3, 6, 9, 12, 15, 18, 21 and 24 for the surveillance of bladder tumors. During the months that instillations will be performed, cystoscopies will be conducted only once at each of these months. During the Follow-up Phase, cystoscopies will be performed at months 30, 36, 42, 48, 54 and 60.
Mandatory bladder biopsies will be done for all patients at month 6.
During the course of the study, biopsies will be taken only if evident or suspicious lesions are seen during cystoscopy or in case of negative cystoscopy but positive cytology.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 129
- Patients refractory to BCG therapy;
- Patients with histologically confirmed diagnosis of high grade lesions;
- Diagnosis of high grade lesion must be within 56 days prior to beginning of study treatment;
- Have had all visible papillary lesion(s) resected by TURBT within 56 days prior to beginning of study treatment;
- Available for the whole duration of the study including follow-up (60 months);
- Life expectancy of > 5 years;
- Patients with an ECOG performance status grade of 2 or less;
- Absence of urothelial carcinoma involving the upper urinary tract or prostatic urethra within 12 months from beginning of study treatment;
- Able to understand and give written informed consent;
- In the investigator's judgment, the patient is able to participate in the study.
- Current or previous history of muscle invasive tumors;
- Current or previous history of lymph node or distant metastases from bladder cancer;
- Current systemic cancer therapy;
- Current or prior pelvic external beam radiotherapy;
- Pelvic brachytherapy within 2 years of study entry;
- Prior treatment with MCC;
- Patients with existing urinary tract infection or recurrent severe bacterial cystitis;
- Clinically significant and unexplained elevations of liver or renal function tests;
- White blood cell count below 3 x109/L (3,000/mm3) or platelet count below 100 x 109/L(100,000/mm3);
- Severe cardiovascular disease;
- Women who are pregnant or lactating;
- Congenital or acquired immune deficiency;
- With history of malignancy of any organ system, treated or untreated, within the past 5 years (with the exception of adequately treated basal cell or squamous cell carcinoma of the skin, stage T1 prostate cancer, carcinoma in situ of the cervix or colon polyps);
- Previous investigational treatment within 3 months from beginning of study treatment;
- Patients who cannot hold the instillation for one hour;
- Patients who cannot tolerate intravesical administration or intravesical surgical manipulation (cystoscopy or biopsy);
- Clinically significant active infections;
- Any medical or psychiatric condition which, in the opinion of the investigator, would preclude the participant from adhering to the protocol or completing the trial per protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Mycobacterial cell wall-DNA complex Mycobacterial cell wall-DNA complex Mycobacterial cell wall-DNA complex
- Primary Outcome Measures
Name Time Method One year disease-free survival rate Prospective
- Secondary Outcome Measures
Name Time Method Duration of disease-free survival in all patients Prospective Time to progression to muscle invasive disease Prospective Overall survival in all patients Prospective Rate of overall drug-related adverse events leading to two consecutive treatment delays of one week each or to the discontinuation of treatment. Prospective The 3, 6 and 24 month disease-free survival rate Prospective
Trial Locations
- Locations (31)
Andreou Research
🇨🇦Surrey, British Columbia, Canada
Can-Med Clinical Research
🇨🇦Victoria, British Columbia, Canada
Dr. Steinhoff Clinical Research
🇨🇦Victoria, British Columbia, Canada
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
The University of Chicago Hospitals
🇺🇸Chicago, Illinois, United States
Sheldon J Freedman, MD, Ltd
🇺🇸Las Vegas, Nevada, United States
Chesapeake Urology Research Associates
🇺🇸Towson, Maryland, United States
Triangle Urology Group
🇺🇸Pittsburgh, Pennsylvania, United States
Memorial Sloan Kettering Cancer Centre
🇺🇸New York, New York, United States
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Centre Hospitalier de l'Universite de Montreal
🇨🇦Montreal, Quebec, Canada
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Centre de Recherche du CHUQ
🇨🇦Quebec City, Quebec, Canada
San Diego Clinical Trials
🇺🇸San Diego, California, United States
BCG Oncology
🇺🇸Phoenix, Arizona, United States
Connecticut Urological Research at Grove Hill
🇺🇸New Britain, Connecticut, United States
University of Miami School of Medicine
🇺🇸Miami, Florida, United States
Winter Park Urology Associates P.A.
🇺🇸Orlando, Florida, United States
Welborn Clinic
🇺🇸Evansville, Indiana, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Urology Clinics of North Texas, P.A.
🇺🇸Dallas, Texas, United States
M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Hudson Valley Urology
🇺🇸Poughkeepsie, New York, United States
Sentara Medical Group - Urology of Virginia, PC
🇺🇸Norfolk, Virginia, United States
Delaware Valley Urology, LLC-Voorhees
🇺🇸Voorhees, New Jersey, United States
Centre for Applied Urological Research
🇨🇦Kingston, Ontario, Canada
Urology San Antonio Research, PA
🇺🇸San Antonio, Texas, United States
University Health Network / Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
The Male Health Center
🇨🇦Toronto, Ontario, Canada