Clinical trial NCT00406068: Mycobacterial Cell Wall-DNA Complex in Treatment of BCG-refractory Patients With Non-muscle Invasive Bladder Cancer
Official title: Open-label, Multi-center Study of the Efficacy and Safety of MCC in the Treatment of Patients With Non-muscle Invasive (Superficial) Bladder Cancer at High Risk of Progression and Who Are Refractory to BCG
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Bladder Neoplasms
Keywords: Bladder neoplasm
Intravesical drug administration
Neoplasm recurrence, local
Transitional cell, carcinoma
Carcinoma in situ
Mycobacterium
Lead sponsor: Bioniche Life Sciences Inc.
Sponsor class: INDUSTRY
First posted: 2006-12-04
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: One year disease-free survival rate
timeFrame: Prospective
Secondary outcomes:
measure: The 3, 6 and 24 month disease-free survival rate
timeFrame: Prospective
measure: Duration of disease-free survival in all patients
timeFrame: Prospective
measure: Time to progression to muscle invasive disease
timeFrame: Prospective
measure: Overall survival in all patients
timeFrame: Prospective
measure: Rate of overall drug-related adverse events leading to two consecutive treatment delays of one week each or to the discontinuation of treatment.
timeFrame: Prospective
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: BCG Oncology
state: Arizona
city: San Diego
country: United States
facility: San Diego Clinical Trials
state: California
city: New Britain
country: United States
facility: Connecticut Urological Research at Grove Hill
state: Connecticut
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Orlando
country: United States
facility: Winter Park Urology Associates P.A.
state: Florida
city: Chicago
country: United States
facility: The University of Chicago Hospitals
state: Illinois
city: Evansville
country: United States
facility: Welborn Clinic
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Towson
country: United States
facility: Chesapeake Urology Research Associates
state: Maryland
city: Las Vegas
country: United States
facility: Sheldon J Freedman, MD, Ltd
state: Nevada
city: Voorhees
country: United States
facility: Delaware Valley Urology, LLC-Voorhees
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Centre
state: New York
city: Poughkeepsie
country: United States
facility: Hudson Valley Urology
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Pittsburgh
country: United States
facility: Triangle Urology Group
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Urology Clinics of North Texas, P.A.
state: Texas
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Urology San Antonio Research, PA
state: Texas
city: Norfolk
country: United States
facility: Sentara Medical Group - Urology of Virginia, PC
state: Virginia
city: Surrey
country: Canada
facility: Andreou Research
state: British Columbia
city: Victoria
country: Canada
facility: Can-Med Clinical Research
state: British Columbia
city: Victoria
country: Canada
facility: Dr. Steinhoff Clinical Research
state: British Columbia
city: Kingston
country: Canada
facility: Centre for Applied Urological Research
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network / Princess Margaret Hospital
state: Ontario
city: Toronto
country: Canada
facility: The Male Health Center
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Quebec City
country: Canada
facility: Centre de Recherche du CHUQ
state: Quebec
Study officials:
affiliation: Centre for Applied Urological Research, Kingston General Hospital/Queen's University
name: Alvaro Morales, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Morales A, Herr H, Steinberg G, Given R, Cohen Z, Amrhein J, Kamat AM. Efficacy and safety of MCNA in patients with nonmuscle invasive bladder cancer at high risk for recurrence and progression after failed treatment with bacillus Calmette-Guerin. J Urol. 2015 Apr;193(4):1135-43. doi: 10.1016/j.juro.2014.09.109. Epub 2014 Oct 5.