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 (EMBARC-RF)

This study has been terminated.
(Lack of Recruitment)
Sponsor:
Information provided by (Responsible Party):
Bioniche Life Sciences Inc.
ClinicalTrials.gov Identifier:
NCT01200992
First received: September 12, 2010
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Bladder Neoplasm
Intravesical Drug Administration
Neoplasm Recurrence, Local
Transitional Cell, Carcinoma
Carcinoma in Situ
Mycobacterium
Biological: EN3348
Biological: Mitomycin C
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bioniche Life Sciences Inc.:

Primary Outcome Measures:
  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment: 84
Study Start Date: November 2010
Study Completion Date: December 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EN3348
8 mg mixed with sterile water for injection for a total volume of 50mL
Biological: EN3348
Induction: 6 weekly instillations. Maintenance: Monthly instillations to Month 12
Active Comparator: Mitomycin C
40 mg powder will be reconstituted with sterile water for injection to a total volume of 40 mL
Biological: Mitomycin C
Induction: 6 weekly instillations. Maintenance: Monthly instillations to Month 12

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01200992

  Show 72 Study Locations
Sponsors and Collaborators
Bioniche Life Sciences Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Bioniche Life Sciences Inc.
ClinicalTrials.gov Identifier: NCT01200992     History of Changes
Other Study ID Numbers: EN3348-303
Study First Received: September 12, 2010
Last Updated: December 18, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency
India: Central Drugs Standard Control Organization
Ukraine: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Germany: Federal Institute for Drugs and Medical Devices
Australia: Department of Health and Ageing Therapeutic Goods Administration
New Zealand: Ministry of Health

Keywords provided by Bioniche Life Sciences Inc.:
Urinary Bladder Neoplasms
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Mycobacterial cell wall DNA complex

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Neoplasms
Carcinoma
Carcinoma in Situ
Mycobacterium Infections
Neoplasm Recurrence, Local
Recurrence
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Neoplastic Processes
Pathologic Processes
Disease Attributes
Mitomycins
Mitomycin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Alkylating Agents

ClinicalTrials.gov processed this record on July 24, 2014