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

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

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).

Study Overview

• Status: Completed
• Conditions: Bladder Neoplasms
• Intervention / Treatment: Drug: Mycobacterial cell wall-DNA complex

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• Patients who are not disease-free (evidence of papillary lesions, CIS or muscle invasive disease) will be withdrawn from further study treatment and will be referred to other therapies at the discretion of the investigator.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 Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 1N1
      • Andreou Research
    • Victoria, British Columbia, Canada, V8V 3N1
      • Dr. Steinhoff Clinical Research
    • Victoria, British Columbia, Canada, V8T 5G1
      • Can-Med Clinical Research
  • Ontario
    • Kingston, Ontario, Canada, K7L 3J7
      • Centre for Applied Urological Research
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • UNIVERSITY HEALTH NETWORK / PRINCESS MARGARET HOSPITAL
    • Toronto, Ontario, Canada, M6A 3B5
      • The Male Health Center
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Montreal, Quebec, Canada, H2X 3J4
      • Centre Hospitalier de l'Universite de Montreal
    • Quebec City, Quebec, Canada, G1R 2J6
      • Centre de recherche du CHUQ
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • BCG Oncology
  • California
    • San Diego, California, United States, 92120
      • San Diego Clinical Trials
  • Connecticut
    • New Britain, Connecticut, United States, 06052
      • Connecticut Urological Research at Grove Hill
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
    • Orlando, Florida, United States, 32803
      • Winter Park Urology Associates P.A.
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Hospitals
  • Indiana
    • Evansville, Indiana, United States, 47713
      • Welborn Clinic
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins University
    • Towson, Maryland, United States, 21204
      • Chesapeake Urology Research Associates
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Sheldon J Freedman, MD, Ltd
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Delaware Valley Urology, LLC-Voorhees
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Centre
    • Poughkeepsie, New York, United States, 12601
      • Hudson Valley Urology
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Triangle Urology Group
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75231
      • Urology Clinics of North Texas, P.A.
    • Houston, Texas, United States, 77030
      • M.D. Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • Urology San Antonio Research, PA
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Sentara Medical Group - Urology of Virginia, PC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
One year disease-free survival rate	Prospective

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Bioniche Life Sciences Inc.
• Investigators: Principal Investigator: Alvaro Morales, MD, Centre for Applied Urological Research, Kingston General Hospital/Queen's University

Publications and helpful links

General Publications

• 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.

Helpful Links

• Publication that includes results for this study.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (ACTUAL): July 1, 2011
• Study Completion (ACTUAL): July 1, 2011

Study Registration Dates

• First Submitted: December 1, 2006
• First Submitted That Met QC Criteria: December 1, 2006
• First Posted (ESTIMATE): December 4, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): July 28, 2016
• Last Update Submitted That Met QC Criteria: July 26, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Carcinoma in situ; Bladder neoplasm; Intravesical drug administration; Neoplasm recurrence, local; Transitional cell, carcinoma; Mycobacterium
• Additional Relevant MeSH Terms: Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Neoplasms; Urinary Bladder Neoplasms
• Other Study ID Numbers: HIS-0611-0602