Efficacy and Safety Evaluation of EN3348 (Mycobacterial Cell Wall-DNA Complex [MCC]) as Compared With Mitomycin C in the Intravesical Treatment of Subjects With BCG Recurrent/Refractory Non-muscle Invasive Bladder Cancer

NCT ID: NCT01200992

Last Updated: 2017-08-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 84 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2013-12-31

Brief Summary

This is a phase 3 randomized, active-controlled, open-label, multicenter study that will be conducted in approximately 120 investigational sites worldwide. Subjects with either recurrent or refractory NMIBC (Ta high grade, T1 low or high grade, CIS) will be eligible for participation in this study.

Refractory disease is defined as evidence of persistent high grade bladder cancer (Ta HG, T1, and/or CIS) at least 6 months from the start of a full induction course of BCG with or without maintenance/re-treatment at 3 months.

Recurrent disease is defined as reappearance of disease after achieving a tumor-free status by 6 months following a full induction course of BCG with or without maintenance/re-treatment at 3 months. Subjects with recurrent disease must have recurred within 18 months following the last dose of BCG.

Approximately 450 subjects will be randomized. The primary objective of this study is to evaluate the efficacy of intravesical EN3348 as compared with mitomycin C in the treatment of subjects with recurrent or refractory NMIBC. The secondary objective is to evaluate the safety of EN3348 as compared with mitomycin C in the treatment of subjects with BCG recurrent or refractory NMIBC. This study will consist of 4 phases: Screening, Induction, Maintenance and Follow-Up and will be conducted over 3 years.

Conditions

Bladder Neoplasm; Neoplasm Recurrence, Local; Transitional Cell, Carcinoma; Carcinoma in Situ; Mycobacterium

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

EN3348

8 mg mixed with sterile water for injection for a total volume of 50mL

Group Type: EXPERIMENTAL

EN3348

Intervention Type: BIOLOGICAL

Induction: 6 weekly instillations. Maintenance: Monthly instillations to Month 12

Mitomycin C

40 mg powder will be reconstituted with sterile water for injection to a total volume of 40 mL

Group Type: ACTIVE_COMPARATOR

Mitomycin C

Intervention Type: BIOLOGICAL

Induction: 6 weekly instillations. Maintenance: Monthly instillations to Month 12

Interventions

EN3348

Induction: 6 weekly instillations. Maintenance: Monthly instillations to Month 12

Intervention Type: BIOLOGICAL

Mitomycin C

Induction: 6 weekly instillations. Maintenance: Monthly instillations to Month 12

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Is 18 years of age and older at time of consent signing
• Have either BCG recurrent or refractory NMIBC:

• Refractory disease is defined as evidence of persistent high grade bladder cancer (Ta HG, T1 and/or CIS) at least 6 months from the start of a full induction course of BCG with or without maintenance/re-treatment at 3 months
• Recurrent disease is defined as reappearance of disease after achieving a tumor-free status by 6 months following a full induction course of BCG with or without maintenance/re-treatment at 3 months. Subjects with recurrent disease must have recurred within 18 months following the last dose of BCG

• A full induction course of BCG is defined as at least 5 out of 6 total expected instillations of BCG within a period of 2 months, regardless of dose strength
• Have histologically confirmed NMIBC (according to 2004 WHO classification) within 8 weeks prior to randomization

• High grade Ta papillary lesion(s)
• High or low grade T1 papillary lesion(s)(biopsy sample must include evidence of muscularis propria)
• CIS, with or without Ta or T1 papillary tumor(s) of any grade
• Have had all visible papillary and resectable CIS lesion(s) removed by TURBT within 8 weeks prior to randomization
• Available for the duration of the study including follow-up (approximately 36 months)
• Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of 2 or less
• Have no evidence of urothelial carcinoma involving the upper urinary tract or the urethra (confirmed by extravesical work up, which may include radiological imaging and/or biopsy) within 6 months of randomization:

• If previous work up occurred more than 6 months from randomization, extravesical work up must be repeated prior to randomization in order to determine eligibility
• Subjects (male and female) of child-bearing potential (including female subjects who are post-menopausal for less than 1 year) must be willing to practice effective contraception (as defined by the Investigator) during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment
• Is able to understand and give written informed consent

Exclusion Criteria

• Current or previous history of muscle invasive bladder tumors
• Current or previous history of lymph node positive and/or metastatic bladder cancer
• Current evidence of pure squamous cell carcinoma, pure adenocarcinoma or pure undifferentiated carcinoma of the bladder
• Currently receiving systemic cancer therapy (cytotoxic/cytostatic or immunotherapy)
• Currently receiving treatment with a prohibited therapy
• Current or prior history of systemic lupus erythematosus
• Systemic immunotherapy within 6 months of randomization
• Treatment with an investigational agent within 30 days or 5 half lives from randomization, whichever is longer
• Prior treatment with an intravesical chemotherapeutic agent within 3 months of randomization except for single perioperative dose of chemotherapy immediately post-TURBT
• Prior treatment with EN3348 (MCC) or any other mycobacterial cell wall composition or formulation
• Refractory to mitomycin C (failure to achieve tumor-free status following minimum of a 6 week induction course of mitomycin C)
• Contraindication to mitomycin C
• Untreated urinary tract or bladder infection
• ANC <1000/µL and hemoglobin <10 g/dL
• Known cardiovascular disease such as myocardial infarction within the past 3 months, unstable angina pectoris, congestive heart failure (NYHA Class III or IV) or uncontrolled cardiac arrhythmia
• Female subjects who are pregnant or lactating
• Congenital or acquired immune deficiency
• Have current or history of documented or suspected malignancy of any organ system (diagnosed, treated or untreated) within the past 5 years (with the exception of localized transitional cell carcinoma of the ureter treated with ureterectomy or nephroureterectomy, adequately treated basal cell or squamous cell carcinoma of the skin or asymptomatic non-metastatic prostate cancer either previously successfully treated or currently under active surveillance or receiving hormone therapy only)
• Bladder contracture or history of an inability to retain the instillate for a minimum of 1 hour, even with premedication
• Inability to 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bioniche Life Sciences Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Alaska Clinical Research Center, LLC

Anchorage, Alaska, United States

BCG Oncology, PC

Phoenix, Arizona, United States

Arizona Urologic Specialists

Tucson, Arizona, United States

Urology Specialists of Southern California - Burbank

Burbank, California, United States

Urology Specialist of Southern California - Encino

Encino, California, United States

American Institute of Research

Los Angeles, California, United States

San Diego Clinical Trials

San Diego, California, United States

West Coast Clinical Research

Tarzana, California, United States

Urology Specialists of Southern California - Torrance

Torrance, California, United States

The Urology Center of Colorado

Denver, Colorado, United States

Genitourinary Surgical Consultants, PC

Denver, Colorado, United States

Urology Associates

Englewood, Colorado, United States

University of Connecticut Health Center

Farmington, Connecticut, United States

Grove Hill Medical Center

New Britain, Connecticut, United States

Florida Urological Associates, PA

Coral Springs, Florida, United States

Urological Research Network

Hialeah, Florida, United States

Urology Health Team, PLLC

Ocala, Florida, United States

Advanced Research Institute, Inc.

Trinity, Florida, United States

Northwestern Medicine

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Deaconess Clinic, Inc.

Evansville, Indiana, United States

Northeast Indiana Research, LLC

Fort Wayne, Indiana, United States

Kansas City Urology Care, P.A.

Overland Park, Kansas, United States

University of Maryland

Baltimore, Maryland, United States

Chesapeake Urology Research Associates

Baltimore, Maryland, United States

Corbin Clinical Resources

Cumberland, Maryland, United States

Chesapeake Urology Research Associates

Glen Burnie, Maryland, United States

Myron I. Murdock, MD, LLC

Greenbelt, Maryland, United States

Chesapeake Urology Research Associates

Towson, Maryland, United States

Bay State Urologists

Watertown, Massachusetts, United States

Michigan Institute of Urology

Troy, Michigan, United States

Delaware Valley Urology, LLC Burlington

Mount Laurel, New Jersey, United States

Delaware Valley Urology

Voorhees Township, New Jersey, United States

The Capital Region Medical Research Foundation, Inc.

Albany, New York, United States

Accumed Research Associates

Garden City, New York, United States

Columbia University Medical Center

New York, New York, United States

Premier Medical Group of the Hudson Valley

Poughkeepsie, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

TriState Urologic Services PSC, Inc.

Cincinnati, Ohio, United States

Columbus Urology

Columbus, Ohio, United States

Signal Point Clinical Research Center, LLC

Middletown, Ohio, United States

Unison Clinical Research

Toledo, Ohio, United States

Parkhurst Research Organization, LLC

Bethany, Oklahoma, United States

Urologic Consultants of SE PA

Bala-Cynwyd, Pennsylvania, United States

Urology Health Specialists, LLC

Bryn Mawr, Pennsylvania, United States

Ilumina Clinical Associates

Indiana, Pennsylvania, United States

Triangle Urological Group

Pittsburgh, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Mount Nittany Physician Group

State College, Pennsylvania, United States

Pharma Resource

East Providence, Rhode Island, United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Urology Associates of North Texas

Arlington, Texas, United States

Urology Clinics of North Texas, PA

Dallas, Texas, United States

Urology Associates of South Texas

McAllen, Texas, United States

Virginia Urology

Richmond, Virginia, United States

Southern Interior Medical Research, Inc.

Kelowna, British Columbia, Canada

Pacific Urologic Research

Victoria, British Columbia, Canada

London Health Sciences Centre

London, Ontario, Canada

Mor Urology Inc.

Newmarket, Ontario, Canada

Office of Dr. Bernard Goldfarb

North Bay, Ontario, Canada

The Fe/Male Health Centres

Oakville, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Princess Margaret Hospital - University Health Network

Toronto, Ontario, Canada

Centre Hospitalier Universitaire de Quebec- L'Hotel-Dieu de Quebec

Québec, Quebec, Canada

GUT (Society of Urologic Innovative Therapies), GbR

Kirchheim unter Teck, , Germany

Universitair Medisch Centrum St Radboud, Department of Urology

Nijmegen, , Netherlands

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Oddział Urologii, Samodzielny Publiczny Szpital Kliniczny Nr 4 w Lublinie [Department of Urology, Independent Public Teaching Hospital #4 in Lublin]

Lublin, , Poland

Maria Sklodowska-Curie Institute of Oncology

Warsaw, , Poland

Wojewódzki Szpital Specjalistyczny we Wrocławiu

Wroclaw, , Poland

Nottingham Urology Centre, NHS Trust

Nottingham, , United Kingdom

Countries

United States; Canada; Germany; Netherlands; Poland; United Kingdom

Other Identifiers

EN3348-303

Identifier Type: -

Identifier Source: org_study_id