Mycobacterial Cell Wall-DNA Complex in Treatment of BCG-refractory Patients With Non-muscle Invasive Bladder Cancer

Sponsor

Bioniche Life Sciences Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00406068

Collaborator

(none)

129

Enrollment

Locations

Arm

Duration (Months)

4.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Bladder Neoplasms	Drug: Mycobacterial cell wall-DNA complex	Phase 2/Phase 3

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Patients who are not disease-free (evidence of papillary lesions, CIS or muscle invasive disease) will be withdrawn from further study treatment and will be referred to other therapies at the discretion of the investigator.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.

Study Design

Study Type:

Interventional

Actual Enrollment :

129 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Nov 1, 2006

Actual Primary Completion Date :

Jul 1, 2011

Actual Study Completion Date :

Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mycobacterial cell wall-DNA complex Mycobacterial cell wall-DNA complex	Drug: Mycobacterial cell wall-DNA complex 8 mg MCC, intravesical - Induction Phase (6 weekly intravesical instillations) and Maintenance Phase (3 weekly instillations at months 3, 6, 12, 18 and 24). Other Names: MCC - Urocidin

Arm

Intervention/Treatment

Experimental: Mycobacterial cell wall-DNA complex

Mycobacterial cell wall-DNA complex

Drug: Mycobacterial cell wall-DNA complex

8 mg MCC, intravesical - Induction Phase (6 weekly intravesical instillations) and Maintenance Phase (3 weekly instillations at months 3, 6, 12, 18 and 24).

Other Names:

MCC - Urocidin

Outcome Measures

Primary Outcome Measures

One year disease-free survival rate [Prospective]

Secondary Outcome Measures

The 3, 6 and 24 month disease-free survival rate [Prospective]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	BCG Oncology	Phoenix	Arizona	United States	85032
2	San Diego Clinical Trials	San Diego	California	United States	92120
3	Connecticut Urological Research at Grove Hill	New Britain	Connecticut	United States	06052
4	University of Miami School of Medicine	Miami	Florida	United States	33136
5	Winter Park Urology Associates P.A.	Orlando	Florida	United States	32803
6	The University of Chicago Hospitals	Chicago	Illinois	United States	60637
7	Welborn Clinic	Evansville	Indiana	United States	47713
8	Johns Hopkins University	Baltimore	Maryland	United States	21231
9	Chesapeake Urology Research Associates	Towson	Maryland	United States	21204
10	Sheldon J Freedman, MD, Ltd	Las Vegas	Nevada	United States	89148
11	Delaware Valley Urology, LLC-Voorhees	Voorhees	New Jersey	United States	08043
12	Memorial Sloan Kettering Cancer Centre	New York	New York	United States	10021
13	Hudson Valley Urology	Poughkeepsie	New York	United States	12601
14	University of Rochester Medical Center	Rochester	New York	United States	14642
15	Triangle Urology Group	Pittsburgh	Pennsylvania	United States	15212
16	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
17	Urology Clinics of North Texas, P.A.	Dallas	Texas	United States	75231
18	M.D. Anderson Cancer Center	Houston	Texas	United States	77030
19	Urology San Antonio Research, PA	San Antonio	Texas	United States	78229
20	Sentara Medical Group - Urology of Virginia, PC	Norfolk	Virginia	United States	23502
21	Andreou Research	Surrey	British Columbia	Canada	V3V 1N1
22	Can-Med Clinical Research	Victoria	British Columbia	Canada	V8T 5G1
23	Dr. Steinhoff Clinical Research	Victoria	British Columbia	Canada	V8V 3N1
24	Centre for Applied Urological Research	Kingston	Ontario	Canada	K7L 3J7
25	London Health Sciences Centre	London	Ontario	Canada	N6A 5W9
26	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada	M4N 3M5
27	University Health Network / Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
28	The Male Health Center	Toronto	Ontario	Canada	M6A 3B5
29	Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec	Canada	H2X 3J4
30	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
31	Centre de Recherche du CHUQ	Quebec City	Quebec	Canada	G1R 2J6