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Bladder NeoplasmPhase 3EMBARC-RFNCT01200992

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

A Phase 3 study testing EN3348 and Mitomycin C in people with Bladder Neoplasm and Neoplasm Recurrence, Local, run by Bioniche Life Sciences Inc. at 72 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
EN3348 and Mitomycin C
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
84 participants
Where
72 sitesin 6 countries
Study dates
Nov 2010to Dec 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 16Show fewer
  • 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

Who cannot join

  • 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
Show all 22Show fewer
  • 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

Trial locations and contacts

72 sites in 6 countries.

72 sites in 6 countries

United States56 sites

  • The Capital Region Medical Research Foundation, Inc.

    Albany, New York, 12208

  • Alaska Clinical Research Center, LLC

    Anchorage, Alaska, 99508

  • Urology Associates of North Texas

    Arlington, Texas, 76017

  • Urologic Consultants of SE PA

    Bala-Cynwyd, Pennsylvania, 19004

  • University of Maryland

    Baltimore, Maryland, 21201

  • Chesapeake Urology Research Associates

    Baltimore, Maryland, 21237

  • Parkhurst Research Organization, LLC

    Bethany, Oklahoma, 73008

  • Urology Health Specialists, LLC

    Bryn Mawr, Pennsylvania, 19010

  • Urology Specialists of Southern California - Burbank

    Burbank, California, 91505

  • Northwestern Medicine

    Chicago, Illinois, 60611

  • University of Chicago

    Chicago, Illinois, 60637

  • TriState Urologic Services PSC, Inc.

    Cincinnati, Ohio, 45212

  • Columbus Urology

    Columbus, Ohio, 43220

  • Florida Urological Associates, PA

    Coral Springs, Florida, 33071

  • Corbin Clinical Resources

    Cumberland, Maryland, 21502

  • Urology Clinics of North Texas, PA

    Dallas, Texas, 75231

  • The Urology Center of Colorado

    Denver, Colorado, 80211

  • Genitourinary Surgical Consultants, PC

    Denver, Colorado, 80220

  • Pharma Resource

    East Providence, Rhode Island, 02915

  • Urology Specialist of Southern California - Encino

    Encino, California, 91436

  • Urology Associates

    Englewood, Colorado, 80113

  • Deaconess Clinic, Inc.

    Evansville, Indiana, 47713

  • University of Connecticut Health Center

    Farmington, Connecticut, 06030

  • Northeast Indiana Research, LLC

    Fort Wayne, Indiana, 46825

  • Accumed Research Associates

    Garden City, New York, 11530

  • Chesapeake Urology Research Associates

    Glen Burnie, Maryland, 21061

  • Myron I. Murdock, MD, LLC

    Greenbelt, Maryland, 20770

  • Urological Research Network

    Hialeah, Florida, 33016

  • Ilumina Clinical Associates

    Indiana, Pennsylvania, 15701

  • American Institute of Research

    Los Angeles, California, 90017

  • Urology Associates of South Texas

    McAllen, Texas, 78503

  • Signal Point Clinical Research Center, LLC

    Middletown, Ohio, 45042

  • Delaware Valley Urology, LLC Burlington

    Mount Laurel, New Jersey, 08054

  • Carolina Urologic Research Center

    Myrtle Beach, South Carolina, 29572

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Grove Hill Medical Center

    New Britain, Connecticut, 06052

  • Columbia University Medical Center

    New York, New York, 10032

  • Urology Health Team, PLLC

    Ocala, Florida, 34474

  • Kansas City Urology Care, P.A.

    Overland Park, Kansas, 66211

  • BCG Oncology, PC

    Phoenix, Arizona, 85032

  • Triangle Urological Group

    Pittsburgh, Pennsylvania, 15212

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15232

  • Premier Medical Group of the Hudson Valley

    Poughkeepsie, New York, 12601

  • Virginia Urology

    Richmond, Virginia, 23235

  • San Diego Clinical Trials

    San Diego, California, 92120

  • Mount Nittany Physician Group

    State College, Pennsylvania, 16801

  • West Coast Clinical Research

    Tarzana, California, 91356

  • Montefiore Medical Center

    The Bronx, New York, 10467

  • Unison Clinical Research

    Toledo, Ohio, 43615

  • Urology Specialists of Southern California - Torrance

    Torrance, California, 90505

  • Chesapeake Urology Research Associates

    Towson, Maryland, 21204

  • Advanced Research Institute, Inc.

    Trinity, Florida, 34655

  • Michigan Institute of Urology

    Troy, Michigan, 48084

  • Arizona Urologic Specialists

    Tucson, Arizona, 85712

  • Delaware Valley Urology

    Voorhees Township, New Jersey, 08043

  • Bay State Urologists

    Watertown, Massachusetts, 02472

Other trials in United States

Canada9 sites

  • Southern Interior Medical Research, Inc.

    Kelowna, British Columbia, V1Y 2H4

  • London Health Sciences Centre

    London, Ontario, N6A 5W9

  • Mor Urology Inc.

    Newmarket, Ontario, L3X 1W1

  • Office of Dr. Bernard Goldfarb

    North Bay, Ontario, P1B 7K8

  • The Fe/Male Health Centres

    Oakville, Ontario, L6H 3P1

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

    Québec, Quebec, G1R 3S1

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

  • Princess Margaret Hospital - University Health Network

    Toronto, Ontario, M5G 2M9

  • Pacific Urologic Research

    Victoria, British Columbia, V8V 3N1

Other trials in Canada

Poland4 sites

  • Uniwersyteckie Centrum Kliniczne

    Gdansk, 80-952

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

    Lublin, 20-954

  • Maria Sklodowska-Curie Institute of Oncology

    Warsaw, 20-781

  • Wojewódzki Szpital Specjalistyczny we Wrocławiu

    Wroclaw, 51-124

Other trials in Poland

Germany1 site

  • GUT (Society of Urologic Innovative Therapies), GbR

    Kirchheim unter Teck, 73230

Other trials in Germany

Netherlands1 site

  • Universitair Medisch Centrum St Radboud, Department of Urology

    Nijmegen, 6525

Other trials in Netherlands

United Kingdom1 site

  • Nottingham Urology Centre, NHS Trust

    Nottingham, NG5 1PB

Other trials in United Kingdom

About this study

Official title: A Phase 3, Randomized, Active-Controlled, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of EN3348 (MCC) as Compared With Mitomycin C in the Intravesical Treatment of Subjects With BCG Recurrent or Refractory Non-Muscle Invasive Bladder Cancer

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.

Read more

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.

Being tested
EN3348, Mitomycin C
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
Medical subject headings
Urinary Bladder Neoplasms, Neoplasm Recurrence, Local, Carcinoma, Transitional Cell, Carcinoma in Situ, Mycobacterium Infections, Neoplasms, Urologic Neoplasms, Urogenital Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EN3348Biological

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

  • Mitomycin CBiological

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

Study groups in NCT01200992
Study groupRoleWhat they receive
EN3348Experimental8 mg mixed with sterile water for injection for a total volume of 50mL
Receives: Biological: EN3348
Mitomycin CActive comparator40 mg powder will be reconstituted with sterile water for injection to a total volume of 40 mL
Receives: Biological: Mitomycin C

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 1 year

Secondary outcomes (1)

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

    Safety endpoint displayed includes adverse events (other than serious adverse events) with a frequency threshold of 5% or greater, for each treatment arm. No statistical comparisons have been performed between the 2 treatment arms.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2010 (estimated)
  2. Study startNov 2010
  3. Primary completionApr 2013
  4. Study completionDec 2013

Why it stopped: Lack of Recruitment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
84 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01200992
Sponsor's protocol ID
EN3348-303
Acronym
EMBARC-RF
Status last verified
Aug 2017
First submitted
12 Sep 2010
Last updated
24 Aug 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing EN3348 and Mitomycin C in people with Bladder Neoplasm and Neoplasm Recurrence, Local, run by Bioniche Life Sciences Inc. at 72 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 72 sites in United States, Canada, Poland, Germany, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Comparison of Event-free Survival of Intravesical EN3348 With Mitomycin C. (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01200992.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2017.

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