| CTRI Number |
CTRI/2012/07/002821 [Registered on: 23/07/2012] Trial Registered Prospectively |
| Last Modified On: |
11/08/2014 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
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Type of Study
|
Biological |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
A clinical trial to study the effects of EN3348 (MCC) as compared with Mitomycin C in the intravesical treatment of subjects with BCG recurrent or refractory non-muscle invasive bladder cancer |
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Scientific Title of Study
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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 |
| Trial Acronym |
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Secondary IDs if Any
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| Secondary ID |
Identifier |
| EN3348-303 Amendment 1 Version 2 dated 25 february 2011 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
|
| Name |
Manali Rane |
| Designation |
Project Manager |
| Affiliation |
DiagnoSearch Life Sciences Pvt. Ltd. |
| Address |
DiagnoSearch Life Sciences Pvt. Ltd
702, Dosti Pinnacle
E-7, Road 22, Wagle EstateThane – 400604.
Tel#: 022-6777 6300
Thane
MAHARASHTRA
400604
India |
| Phone |
02267776300 |
| Fax |
02267776303 |
| Email |
manali.rane@diagnosearch.com |
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Details of Contact Person
Public Query
|
| Name |
Manali Rane |
| Designation |
Project Manager |
| Affiliation |
DiagnoSearch Life Sciences Pvt. Ltd. |
| Address |
DiagnoSearch Life Sciences Pvt. Ltd
702, Dosti Pinnacle
E-7, Road 22, Wagle EstateThane – 400604.
Tel#: 022-6777 6300
MAHARASHTRA
400604
India |
| Phone |
02267776300 |
| Fax |
02267776303 |
| Email |
manali.rane@diagnosearch.com |
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Source of Monetary or Material Support
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Primary Sponsor
|
| Name |
Endo Pharmaceuticals Inc |
| Address |
Endo Pharmaceuticals Inc.
100 Endo Boulevard
Chadds Ford, PA 19317;
United States of America
Telephone: 610-558-9800
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| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
|
| Name |
Address |
| DiagnoSearch Life Sciences Pvt Ltd |
DiagnoSearch Life Sciences Pvt. Ltd
Unit No. 702, 7th Floor,
Dosti Pinnacle,
Plot No. E-7, Road No. 22,
Wagle Industrial Estate,
Thane – 400 604
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Countries of Recruitment
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Canada
Germany
India
Netherlands
Poland
United Kingdom
United States of America |
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Sites of Study
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| No of Sites = 11 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Harvinder Singh |
Chhatrapati Shahuji Maharaj Medical University |
(Erstwhile King George’s Medical University),
New Surgical Block, General Surgery,
Chowk, Lucknow – 226003
Uttar Pradesh, India
Lucknow
UTTAR PRADESH |
9415028046
pahwakgmu@yahoo.co.in |
| Dr Kim J Mammen |
Christian Medical College & Hospital |
Department of Urology,
Brown Road,
Ludhiana – 141 008,
Punjab, India.
Ludhiana
PUNJAB |
0161-5026999
0161-2609958
kjmammen@gmail.com |
| Dr Rajeev Sood |
Dr. Ram Manohar Lohia Hospital & PGIMER |
Department of Urology,
Room no. 31, OPD Block, Baba Kharag Singh Marg,
New Delhi – 110001, India
New Delhi
DELHI |
011-23404323
011-23360067
drsoodr@yahoo.com |
| Dr Desi Gowda Ramesh |
M S Ramaiah Medical College and Hospitals |
New BEL Road,
MSRIT Post,
Bangalore-560054, Karnataka, India
Bangalore
KARNATAKA |
080-22183065
080-22183276
arunacr1@gmail.com |
| Dr Sunder Lal Tolani |
Monilek Hospital & Research Centre |
Department of Research, Room No 105, Basement,
Sector-4, Jawahar Nagar,
Jaipur-302004, Rajasthan, India
Jaipur
RAJASTHAN |
0141-2651393
0141-2652181
sltolani@gmail.com |
| Dr PVLN Murthy |
Nizams Institute of Medical Sciences |
Dept. of Urology and Renal Transplantation,
Punjagutta, Hyderabad-500082, Andhra Pradesh, India
Hyderabad
ANDHRA PRADESH |
040-23489016
040-23323016
pvlnm@rediffmail.com |
| Dr Sudhir Rawal |
Rajiv Gandhi Cancer Institute and Research Centre |
B Block Basement,
Old Building,Sector 5, Rohini,
New Delhi – 110085, India
New Delhi
DELHI |
011-47022027
011-27054092
dr_rawal@hotmail.com |
| Dr Ganesh Bakshi |
Tata Memorial Hospital |
Homi Bhabha Block, 2nd Floor,
Department of Uro-Oncology,
Dr. Ernest Borges Marg, Parel,Mumbai-400012,
Maharashtra, India
Mumbai
MAHARASHTRA |
022-24177000
022-24146937
gkbakshi1973@gmail.com |
| Dr Jitendra Amlani |
Urocare Hospital |
Vidyanagar Main Road,
Oppo. Gokul Hospital,
Rajkot-360002, Gujarat, India
Rajkot
GUJARAT |
0281-2466990
0281-2467060
jcamlani@yahoo.com |
| Dr Nayan Kumar Mohanty |
V. M. Medical College & Safdarjang Hospital |
, Sri Aurobindo Marg, New Delhi - 110029
New Delhi
DELHI |
01126190954
01126190954
nayankm@yahoo.co.in |
| Dr Kalyan Kumar Sarkar |
Woodlands Multispeciality Hospital Limited |
Department of Urology,
8/5, Alipore road,
Kolkata – 700 027
West Bengal, India.
Kolkata
WEST BENGAL |
91-33-24567075
033-24567090
kksarkar@gmail.com |
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Details of Ethics Committee
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| No of Ethics Committees= 11 |
| Name of Committee |
Approval Status |
| Ethical Committee, V.M. Medical College & Safdarjang Hospital |
Approved |
| Ethical Review Board, M.S. Ramaiah Medical College & Teaching Hospital, Bangalore |
Approved |
| Ethics Committee, Woodlands Multispecialty Hospital Limited, Kolkata |
Approved |
| Human Ethics Committee, Tata Memorial Hospital, Mumbai |
Approved |
| Institutional Ethics Committee , Dr. Ram Manohar Lohia Hospital & PGI MER, New Delhi |
Submittted/Under Review |
| Institutional Ethics Committee, Chhatrapati Shahuji Maharaj Medical University(Erstwhile King Goerges Medical University), Lucknow |
Approved |
| Institutional Ethics Committee, Christian Medical College & Hospital, Ludhiana |
Approved |
| Institutional Ethics Committee, Monilek Hospital & Research Center, Jaipur |
Approved |
| Institutional Review Board, Rajiv Gandhi Cancer Institute & Research Centre, New Delhi |
Approved |
| NIMS Institutional Ethics Committee, Nizam’s Institute of Medical Sciences, Hyderabad |
Approved |
| Wellcare Research Ethics Committee, Urocare Hospital, Rajkot |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
BCG Recurrent Or Refractory Non-Muscle Invasive Bladder Cancer
, |
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
EN3348 |
Name of Active Ingredient: Mycobacterial Cell Wall-DNA Complex
Route: Intravesical administration
Dose: 8mg/instillation
Frequency: Induction Phase: Subjects would receive 1 dose/week for 6 weeks of Maintenance Phase: Subjects will receive 1 dose/month for 10 months
|
| Comparator Agent |
Mitomycin C |
Chemotherapeutic agent
Route: Intravesical administration
Dose: 40mg/instillation
Frequency: Induction Phase: Subjects would receive 1 dose/week for 6 weeks
Maintenance Phase: Subjects will receive 1 dose/month for 10 months
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Inclusion Criteria
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| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
Subjects are eligible for inclusion into the study if the following criteria are met:
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 (Ta HG, T1 and/or CIS) at least 6 months from the start of full induction course of BCG1 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 BCG1 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.
1 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) during the study 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
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| ExclusionCriteria |
| Details |
Subjects meeting the following criteria will be excluded from participation in the study:
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
. 6. Current or prior history of systemic lupus erythematosus
7. Systemic immunotherapy within 6 months of randomization
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, except for single perioperative dose of chemotherapy immediately post-TURBT
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)
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. 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 prostrate 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
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Method of Generating Random Sequence
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Stratified randomization |
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Method of Concealment
|
Centralized |
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Blinding/Masking
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Not Applicable |
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Primary Outcome
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| Outcome |
TimePoints |
| The primary objective of this study is to evaluate the efficacy of EN3348 as compared with mitomycin C in the treatment of subjects with BCG recurrent or refractory NMIBC |
The primary outcome is measured as "event free survival"
Event free survival is measured from the time of randomization till an occurance of an event in a subject.
Event is defined as tumor recurrence, tumor progression to muscle invasive bladder cancer
(MIBC) or death, whichever occurs first. |
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Secondary Outcome
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| Outcome |
TimePoints |
| 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. |
• Event-free survival rate at 1 and 2 years
• Recurrence rate at 1 and 2 years
• Progression rate at 1 and 2 years – number of subjects progressing to muscle invasive
disease (T2 or higher) or metastatic bladder cancer observed outside of bladder
• Time to cystectomy – interval from randomization to cystectomy
• Overall survival |
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Target Sample Size
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Total Sample Size="450"
Sample Size from India="70"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
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Phase 3 |
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Date of First Enrollment (India)
|
01/08/2012 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
09/11/2010 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
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Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Other (Terminated) |
| Recruitment Status of Trial (India) |
Other (Terminated) |
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Publication Details
|
Not applicable |
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Individual Participant Data (IPD) Sharing Statement
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Will individual participant data (IPD) be shared publicly (including data dictionaries)?
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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 BCG 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 failure to achieve tumor-free status by 6 months of initiation of adequate BCG therapy (minimum of 5 weekly doses of BCG (induction) followed by a second course (induction or maintenance) in which subject received a minimum of 2 doses).
Recurrent disease is defined as reappearance of disease after achieving a tumor-free status by 6 months after initiation of adequate BCG therapy. Subjects with recurrent disease must have recurred within 18 months following the last dose of BCG.
Approximately 450 subjects will be randomized. The randomization will be 1:1 and stratified by geographic region (North America, India, Europe), tumor pathology (CIS versus no CIS), prior BCG response (refractory versus recurrent), and prior intravesical (IVe) chemotherapy (yes/no). The study will consists of 4 phases: Screening phase of 6 weeks, induction phase of 6 weeks, maintenance phase of 10 months and follow up phase of up to approximately 24 months. |