ot applicable

Conditions: BCG Recurrent or Refractory Non-Muscle Invasive Bladder Cancer
MedDRA version: 14.0Level: LLTClassification code 10022877Term: Invasive bladder cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2011-003496-11-NL

Lead Sponsor: Endo Pharmaceuticals Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 450

Inclusion Criteria

1. Males and females who are 18 years of age or older at time of consent signing
2. Have either BCG recurrent or refractory NMIBC:
a. Refractory disease is defined as evidence of persistent high grade bladder cancer (TaHG, 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
b. 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.
3. Have histologically confirmed NMIBC (according to 2004 WHO classification) within 8 weeks prior to randomization:
a. High grade Ta papillary lesion(s)
b. High or low grade T1 papillary lesion(s) (biopsy sample must include evidence of muscularis propria)
c. CIS, with or without Ta or T1 papillary tumor(s) of any grade
4. Have had all visible papillary and resectable CIS lesion(s) removed by TURBT within 8 weeks prior to randomization
5. Available for the duration of the study including follow-up (approximately 36 months)
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of 2 or less
7. 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 prior to randomization:
a. If previous work up occurred more than 6 months prior to randomization, extravesical work up must be repeated prior to randomization in order to determine eligibility
8. 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) while on treatment and be willing and able to continue contraception for 30 days after their last dose of study treatment
9. Is able to understand and give written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 180
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 270

Exclusion Criteria

1. Current or previous history of muscle invasive bladder tumors
2. Current or previous history of positive lymph nodes and/or metastatic bladder cancer
3. Current evidence of pure squamous cell carcinoma, pure adenocarcinoma or pure undifferentiated carcinoma of the bladder
4. Currently receiving systemic anti-cancer therapy (cytotoxic/cytostatic or immunotherapy)
5. Currently receiving treatment with a prohibited therapy (refer to section 10.2.1, Prohibited Medications)
6. Current or prior history of systemic lupus erythematosus
7. Systemic immunotherapy within 6 months of randomization (refer to section 10.2.1, Prohibited Medications)
8. Treatment with an investigational agent within 30 days or 5 half-lives from randomization, whichever is longer
9. Prior treatment with an intravesical chemotherapeutic agent within 3 months of randomization, with the exception of a single perioperative dose of chemotherapy immediately post-TURBT (not considered treatment)
10. Prior treatment with EN3348 (MCC) or any other mycobacterial cell wall composition or formulation
11. Refractory to mitomycin C (failure to achieve tumor-free status following minimum of a 6-week induction course of mitomycin C) at any time in the subject’s disease history
12. Contraindication to mitomycin C
13. Untreated urinary tract or bladder infection
14. ANC <1000/µL and hemoglobin <10 g/dL
15. Known cardiovascular disease such as myocardial infarction within the past 3 months, unstable angina pectoris, congestive heart failure (New York Heart Association [NYHA] Class III or IV) or uncontrolled cardiac arrhythmia
16. Female subjects who are pregnant or lactating
17. Congenital or acquired immune deficiency
18. 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)
19. Bladder contracture or history of an inability to retain the instillate for a minimum of 1 hour, even with premedication
20. Inability to tolerate intravesical administration or intravesical surgical manipulation (cystoscopy or biopsy)
21. Clinically significant active infections
22. 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