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

NCT01200992 | Terminated Phase 3 Results DMC

• 1 other identifier: EN3348-303
• Study Type: interventional
• Target: 84
• Locations: 6 countries
• Sites: 72

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

Keywords

Urinary Bladder Neoplasms; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urinary Bladder Diseases; Urologic Diseases; Mycobacterial cell wall DNA complex; Intravesical drug administration

Outcome Measures

Primary Outcomes (1)

• Comparison of Event-free Survival of Intravesical EN3348 With Mitomycin C.

  Primary efficacy endpoint will be event-free survival - the interval from randomization to an event. An event is defined as tumor recurrence, tumor progression to muscle invasive bladder cancer or death, whichever occurs first. Tumor recurrence or progression must be documented by bladder biopsy.

  1 year

Secondary Outcomes (1)

• Comparison of Safety of EN3348 With Mitomycin C [Adverse Events (Other Than Serious Adverse Events) With Frequency Threshold of 5% or Greater].

  Through study early termination, approximately 23 months from first subject enrolled.

Study Arms (2)

EN3348

EXPERIMENTAL

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

Biological: EN3348

Mitomycin C

ACTIVE COMPARATOR

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

Biological: Mitomycin C

Interventions

EN3348 BIOLOGICAL

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

EN3348

Mitomycin C BIOLOGICAL

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

Mitomycin C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bioniche Life Sciences Inc.: lead

Study Sites (72)

Alaska Clinical Research Center, LLC

Anchorage, Alaska, 99508, United States

Location

BCG Oncology, PC

Phoenix, Arizona, 85032, United States

Location

Arizona Urologic Specialists

Tucson, Arizona, 85712, United States

Location

Urology Specialists of Southern California - Burbank

Burbank, California, 91505, United States

Location

Urology Specialist of Southern California - Encino

Encino, California, 91436, United States

Location

American Institute of Research

Los Angeles, California, 90017, United States

Location

San Diego Clinical Trials

San Diego, California, 92120, United States

Location

West Coast Clinical Research

Tarzana, California, 91356, United States

Location

Urology Specialists of Southern California - Torrance

Torrance, California, 90505, United States

Location

The Urology Center of Colorado

Denver, Colorado, 80211, United States

Location

Genitourinary Surgical Consultants, PC

Denver, Colorado, 80220, United States

Location

Urology Associates

Englewood, Colorado, 80113, United States

Location

University of Connecticut Health Center

Farmington, Connecticut, 06030, United States

Location

Grove Hill Medical Center

New Britain, Connecticut, 06052, United States

Location

Florida Urological Associates, PA

Coral Springs, Florida, 33071, United States

Location

Urological Research Network

Hialeah, Florida, 33016, United States

Location

Urology Health Team, PLLC

Ocala, Florida, 34474, United States

Location

Advanced Research Institute, Inc.

Trinity, Florida, 34655, United States

Location

Northwestern Medicine

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Deaconess Clinic, Inc.

Evansville, Indiana, 47713, United States

Location

Northeast Indiana Research, LLC

Fort Wayne, Indiana, 46825, United States

Location

Kansas City Urology Care, P.A.

Overland Park, Kansas, 66211, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Chesapeake Urology Research Associates

Baltimore, Maryland, 21237, United States

Location

Corbin Clinical Resources

Cumberland, Maryland, 21502, United States

Location

Chesapeake Urology Research Associates

Glen Burnie, Maryland, 21061, United States

Location

Myron I. Murdock, MD, LLC

Greenbelt, Maryland, 20770, United States

Location

Chesapeake Urology Research Associates

Towson, Maryland, 21204, United States

Location

Bay State Urologists

Watertown, Massachusetts, 02472, United States

Location

Michigan Institute of Urology

Troy, Michigan, 48084, United States

Location

Delaware Valley Urology, LLC Burlington

Mount Laurel, New Jersey, 08054, United States

Location

Delaware Valley Urology

Voorhees Township, New Jersey, 08043, United States

Location

The Capital Region Medical Research Foundation, Inc.

Albany, New York, 12208, United States

Location

Accumed Research Associates

Garden City, New York, 11530, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Premier Medical Group of the Hudson Valley

Poughkeepsie, New York, 12601, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

TriState Urologic Services PSC, Inc.

Cincinnati, Ohio, 45212, United States

Location

Columbus Urology

Columbus, Ohio, 43220, United States

Location

Signal Point Clinical Research Center, LLC

Middletown, Ohio, 45042, United States

Location

Unison Clinical Research

Toledo, Ohio, 43615, United States

Location

Parkhurst Research Organization, LLC

Bethany, Oklahoma, 73008, United States

Location

Urologic Consultants of SE PA

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Urology Health Specialists, LLC

Bryn Mawr, Pennsylvania, 19010, United States

Location

Ilumina Clinical Associates

Indiana, Pennsylvania, 15701, United States

Location

Triangle Urological Group

Pittsburgh, Pennsylvania, 15212, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

Mount Nittany Physician Group

State College, Pennsylvania, 16801, United States

Location

Pharma Resource

East Providence, Rhode Island, 02915, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Urology Associates of North Texas

Arlington, Texas, 76017, United States

Location

Urology Clinics of North Texas, PA

Dallas, Texas, 75231, United States

Location

Urology Associates of South Texas

McAllen, Texas, 78503, United States

Location

Virginia Urology

Richmond, Virginia, 23235, United States

Location

Southern Interior Medical Research, Inc.

Kelowna, British Columbia, V1Y 2H4, Canada

Location

Pacific Urologic Research

Victoria, British Columbia, V8V 3N1, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Mor Urology Inc.

Newmarket, Ontario, L3X 1W1, Canada

Location

Office of Dr. Bernard Goldfarb

North Bay, Ontario, P1B 7K8, Canada

Location

The Fe/Male Health Centres

Oakville, Ontario, L6H 3P1, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Hospital - University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

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

Québec, Quebec, G1R 3S1, Canada

Location

GUT (Society of Urologic Innovative Therapies), GbR

Kirchheim unter Teck, 73230, Germany

Location

Universitair Medisch Centrum St Radboud, Department of Urology

Nijmegen, 6525, Netherlands

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

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

Lublin, 20-954, Poland

Location

Maria Sklodowska-Curie Institute of Oncology

Warsaw, 20-781, Poland

Location

Wojewódzki Szpital Specjalistyczny we Wrocławiu

Wroclaw, 51-124, Poland

Location

Nottingham Urology Centre, NHS Trust

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Neoplasm Recurrence, Local; Carcinoma, Transitional Cell; Carcinoma in Situ; Mycobacterium Infections; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urinary Bladder Diseases; Urologic Diseases

Interventions

Mitomycin

Condition Hierarchy (Ancestors)

Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Aline Hagerimana, MD, Senior Director Clinical Affairs
• Organization: Prometic Biosciences Inc.

a.hagerimana@prometic.com

(514) 781-0115

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2010
• First Posted: September 14, 2010
• Study Start: November 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: December 1, 2013
• Last Updated: August 24, 2017
• Results First Posted: September 11, 2014

Record last verified: 2017-08

Locations

GB (1); DE (1); US (56); NL (1); PL (4); CA (9)