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CTRI Number  CTRI/2013/07/003829 [Registered on: 23/07/2013] Trial Registered Prospectively
Last Modified On: 02/03/2017
Post Graduate Thesis  No 
Type of Trial  BA/BE 
Type of Study    
Study Design  Randomized, Crossover Trial 
Public Title of Study   Comparative study of Doxorubicin HCL Liposome Inj(2mg/mL)(10mL) with Doxil®,20mg in 10mL(2mg/mL)Manf.for:Janssen Products, LP Horsham,PA 19044 administer in female patient with progressed/recurred ovarian cancer after platinum based chemo under fed condition 
Scientific Title of Study   A multicenter, open label, randomized, balanced, two treatment, two period, two sequence, two way crossover, single dose, bioequivalence study of Doxorubicin Hydrochloride Liposome Injection (2mg/mL) (10mL) of Onco Therapies Limited, Bangalore, India with Doxil®Doxorubicin HCl liposome injection, 20mg in 10mL (2 mg/mL) Manufactured by: Ben Venue Laboratories, Inc., Bedford, OH 44146 Manufactured for: Janssen Products, LP Horsham, PA 19044 administered in female patients with ovarian cancer whose disease has progressed or recurred after platinum based chemotherapy under fed condition. 
Trial Acronym   
Secondary IDs if Any  
Secondary ID  Identifier 
12-VIN-274 Version 01 dated 9th July 2012  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Brijesh Wadekar  
Designation  Head of Department  
Affiliation  Veeda Clinical Research Pvt. Ltd.  
Address  Veeda Clinical Research Pvt. Ltd.Insignia, Sindhu Bhavan Road,
Bodakdev Road, S.G.highway. Ahmedabad
Ahmadabad
GUJARAT
380059
India 
Phone  07930013000  
Fax  07930013010  
Email  brijesh.wadekar@veedacr.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Brijesh Wadekar  
Designation  Head of Department  
Affiliation  Veeda Clinical Research Pvt. Ltd.  
Address  Veeda Clinical Research Pvt. Ltd.Insignia, Sindhu Bhavan Road,
Bodakdev Road, S.G.highway. Ahmedabad
Ahmadabad
GUJARAT
380059
India 
Phone  07930013000  
Fax  07930013010  
Email  brijesh.wadekar@veedacr.com  
 
Details of Contact Person
Public Query
 
Name  Dr Brijesh Wadekar  
Designation  Head of Department  
Affiliation  Veeda Clinical Research Pvt. Ltd.  
Address  Veeda Clinical Research Pvt. Ltd.Insignia, Sindhu Bhavan Road,
Bodakdev Road, S.G.highway. Ahmedabad
Ahmadabad
GUJARAT
380059
India 
Phone  07930013000  
Fax  07930013010  
Email  brijesh.wadekar@veedacr.com  
 
Source of Monetary or Material Support  
Onco Therapies Limited.  
 
Primary Sponsor  
Name  Onco Therapies Limited  
Address  Bilekahalli, Bannerghatta Road Bangalore 560076, India  
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 15  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr A V S Suresh  BIBI General Hospital & Cancer center   16-3-991/1/c, Govt Printing press road, Malakpet, Hyderabad, 500024
Hyderabad
ANDHRA PRADESH 
9246243024

sureshattili@yahoo.com 
Dr Smita Gupte  Cancer Clinic  Cancer Clinic, 208 Shreewardhan Complex, Wardha Road, Ramdaspeth AND Cancer Clinic and Nursing Home, block 4B, Hyatt Medicare, Dr. N.B.Khare Marg, Dhantoli
Nagpur
MAHARASHTRA 
09373107176

cancerclinic9@gmail.com 
Dr Ajay mehta  Central India Cancer Research Institute  11, Shankr Nagar, West High Court, Nagpur, 440010 Maharastra
Nagpur
MAHARASHTRA 
09823190192

ajayonco@hotmail.com 
DrGopichand  City Cancer centre  33-25-33, Venkta Krishnayya street suryaraopet, Vijaywada-520002
Krishna
ANDHRA PRADESH 
9642611888

mgopichand@yahoo.com 
Dr Rajinesh Nagarkar  Curie Manavata cancer centre  Opp:Mhamarg Bus Stand,Mumabi,Nasik, Maharastara-422002,INDIA
Nashik
MAHARASHTRA 
09823258862

drraj@manavatacancercentre.com 
Dr K N Srinivasan  Dr. G Vishwanathan Speciality Hospital  No. 27, Babu Road, Trichy-620008
Tiruchirappalli
TAMIL NADU 
9443337230

kns68@yahoo.com 
Dr K velavan  Erode Cancer center Velavan Nagaar  Thindal (PO),Peruindurai Road,Erode-12
Erode
TAMIL NADU 
09629760276

velavandoctor@gmail.com 
Dr Niraj Bhatt  Kailash cancer hospital and Research centre,  kailash cancer hospital and Research centure,Muni seva asharm,Goraj-391760,Ta.Waghodia,Dist. Vadodara
Vadodara
GUJARAT 
09687623125

medonc12@gmail.com 
Dr SP Shrivastav  Life Research center  Life Research center,401-Param Doctor House,station lal darwaja road,Surat-395003
Surat
GUJARAT 
0261-224862

crconcolrc@yahoo.com 
Dr K S Kirushnakumar  Meenakshi mission hospital and research center  Meenakshi mission hospital and research center,Lake area,Merul road,Madurai,Tamilnadu,625107
Madurai
TAMIL NADU 
0452-2586353

drkskk@yahoo.com 
Dr Yatish Kumar  N R R Hospital  Hessaragatta Main Road, Near Chikanbanvara Railways Station, Bangalore,
Bangalore
KARNATAKA 
9986873824

dryathish@hotmail.com 
Dr Rakesh Neve  Nandadeep Multispeciality Hospital  119511,FC Road,Shivaji Nagar, Pune 41105
Pune
MAHARASHTRA 
9881143140

drdipalin@gmail.com 
DrMinish Jain  Noble Hospital Pvt ltd.  153, Magarpatta city road, Hadapsar, Pune 411013 Maharastra
Pune
MAHARASHTRA 
09823133390

minishjain009@gmail.com 
Dr S S Nirni  Omega Hospital,  Road No 12, Banjara Hill, HCA Colony Road, Hyderabad, AndhraPradesh
Hyderabad
ANDHRA PRADESH 
040-23551034

nirni2002@rediffmail.com 
Dr Pradeep Shah  Shreyas Medical Clinic and Hospital  2 Premal Apartment Raopura, Near GPO, Vadodara, Gujarat-390001
Vadodara
GUJARAT 
9714974409

pradeeprshah@msn.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 15  
Name of Committee  Approval Status 
Axon Institutional Ethics Committee/Hyderabad/Dr.S.S.Nirni  Approved 
BIBI Institutional Ethics Committee/Hyderabad/Dr. AVS Suresh  Submittted/Under Review 
Central India Cancer Research Institute/Nagpur/Dr. Ajay Mehta  Submittted/Under Review 
Ethical Review Board, Meenakshi Mission Hospital & Research Centre/Madurai/Dr.Kirushnakumar  Approved 
Hospital Ethics committee/Trichy/Dr.K.Sirinivasan  Submittted/Under Review 
Independent Ethics committee, Manav health Foundation/Vadodara/Dr. Pradeep Shah  Submittted/Under Review 
Institutional Ethics Committee Erode Cancer Centre/Erode/Dr. Velavan  Submittted/Under Review 
Institutional Ethics Committee, City Cancer centre/Vijaywada/Dr.Gopichand  Approved 
Institutional Ethics Committee, NRR Hospital, Bangalore/Bangalore/Dr.Yatishkumar  Approved 
Kailash cancer and Medical centre Institutional Ethics Committee/Vadodara/Dr.Niraj Bhatt  Approved 
Manavata Clinical Research Institute Professional Ethics Committee/Nasik/Dr.Rajnish Nagarkar  Submittted/Under Review 
Nagpur Independent Ethics Committee/Nagpur/Dr. Smita Gupte  Approved 
Nandadeep Hospital Independent Ethics Committee/Pune/Dr.Rakesh Neve  Submittted/Under Review 
Nobel Hospital Institutional Ethics Committee/pune/Dr.Minish Jain  Approved 
Research Independent Ethics Committee, Surat /surat/Dr.S.P.Shrivastav  Submittted/Under Review 
 
Regulatory Clearance Status from DCGI  
Status 
No Objection Certificate 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Ovarian Cancer ,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Doxil®Doxorubicin HCl liposome injection, 20mg in 10mL (2 mg/mL).Dose of 50 mg/meter square will be administered once in every 4 weeks by Intra Venous Infusion.   Manufactured by: Ben Venue Laboratories, Inc., Bedford, OH 44146 Manufactured for: Janssen Products, LP Horsham, PA 19044 
Intervention  Doxorubicin Hydrochloride Liposome Injection. Dose of 50 mg/meter square will be administered once in every 4 weeks by Intra Venous Infusion for four to six cycles.  Onco Therapies Limited, Bangalore, India 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  75.00 Year(s)
Gender  Female 
Details  1.Female 18 to 75 years of age (both inclusive) and having a Body Mass Index (BMI) at least 17 calculated as weight in kg / (height in meter)square.
2.Patients with Ovarian Cancer whose disease has progressed or recurred after Platinum-based Chemotherapy and requiring Doxorubicin HCl liposomal injection 50 mg/meter square dose as monotherapy.
3.Patient should have recovered from any toxic effects of previous chemotherapy as judged by the Investigator.
4.Patients with life expectancy of at least 3 months.
5.ECOG performance status ≤2
6.Patients can be on stable concomitant medication, as long as drugs and their dose have not been changed for the last 3 months prior to first day of dosing.
7.Adequate Hemopoeitic, Renal and Liver function
Body system Parameters
Bone marrow function ANC ≥ 1500/mm3,
Platelet count ≥ 100,000/mm3
Haemoglobin ≥ 9.0 g/dl
Renal function Serum Creatinine < 1.5 times ULN
Hepatic function AST and ALT < 2.5 times ULN
Alkaline phosphatase < 2 times ULN
Bilirubin < 2.5 times ULN
8.Sexually active women, unless surgically sterile (at least 6 months prior to Study drug administration) or postmenopausal for at least 12 consecutive months, must use an effective method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives [any hormonal method in conjunction with a secondary method], intrauterine device, female condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of condom with spermicide by sexual partner or sterile [at least 6 months prior to Study drug administration] sexual partner) for at least 4 weeks prior to study drug administration, during study and up to 30 days after the last dose of study drug. Cessation of birth control after this point should be discussed with a responsible physician.
It is investigator’s responsibility to ensure that above points regarding an effective method of avoiding pregnancy are discussed with patient in detail and patient agreed for this and it is documented in source document. The investigator should ensure that the patient is using an effective method of avoiding pregnancy as per protocol.
9.Subject or his/her legal representative has signed the informed consent.
10.Patients should preferably be on monotherapy. However, cancer patients receiving concomitant drug(s) are allowed to participate, provided:
a.The concomitant medication with dosing regimen is the same for both study period and clearly documented and clearly stated in the protocol.
b.The concurrent medications do not interfere with the assay for measuring the drug in plasma.  
 
ExclusionCriteria 
Details  1.History of allergy or hypersensitivity to Doxorubicin HCl Liposome Injection or any related compound at any dose.
2.Positive pregnancy test at screening (Serum) and prior to dosing (Urine) in each period.
3.Patient who’s total cumulative dose of doxorubicin HCl approaches 550 mg/meter square
4.Patient having active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, P. carinii or other microorganism if under treatment with myelotoxic drugs.
5.Abnormal baseline findings considered by the investigator to indicate conditions that might affect study endpoints.
6.Any clinically significant concomitant disease
7.Alcohol or drug abuse or drug dependence within the preceding year
8.The receipt of an investigational product or participation to another clinical trial within 60 days prior to first day of dosing. of investigational Product (Elimination half-life of the study drug should be taken into consideration for inclusion of the patient in the study).
9.Pregnant or breastfeeding female
10.Patients with a prior history of coronary artery disease or any of the following cardiac conditions:
a.Unstable angina
b.Myocardial infarction within the past 6 months
c.NYHA (New York State Heart Association) class II-IV heart failure
d.Severe uncontrolled ventricular arrhythmias
e.Clinically significant pericardial disease
f.Electrocardiographic evidence of acute ischemic or active conduction system abnormalities.
g.Any other cardiac illness that could lead to a safety risk to the patient in case of enrolment in the study
11.Patients with clinically significant liver or renal disease as judged by the investigator.
12.Known brain metastasis
13.Presence of active infections
14.Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by NCI CTCAE criteria.
15.Patients with hepatic impairment and severe renal impairment
16.A positive hepatitis screen including hepatitis B surface antigen, HCV or HAV (IgM) antibodies
17.Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product for the current study.
18.Known, existing uncontrolled coagulopathy
19.Physiological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
20.Patients must not have taken any potent CYP3A4 inhibitors including but not limited to: ketoconazole, itraconazole, troleandomycin, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, amprenavir, nefazodone, fluvoxamine, diltiazem, verapamil, mibefradil, cimetidine and cyclosporine within 30 days prior to day of first dosing and/or use of drug metabolism enzymes such as phenytoin, cabamazepin, phenobarbital, etc…during the study and within 30 days prior to day of first dosing.
21.Patients with another primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention.
22.Any other condition that, in the investigator’s judgment, might increase the risk to the patient or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study. 
 
Method of Generating Random Sequence   Other 
Method of Concealment   An Open list of random numbers 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Compare and evaluate the single dose,comparative bioavailability study of Doxorubicin HCL Liposome Injection (2 mg/mL)(10mL)of Onco Therapies Limited, Bangalore, India with Doxil®Doxorubicin HCl liposome injection,20mg in 10mL(2 mg/mL) Manufactured by: Ben Venue Lab, Inc., Bedford, OH 44146 Manufactured for: Janssen Products, LP Horsham, PA 19044 administered in female patients with ovarian cancer whose disease has progressed or recurred after platinum based chemotherapy under fed condition.  Total 18 blood samples collected during each period. Pre-infusion blood sample of 3.5 mL(00.00)will be collected within 1 hr prior to dosing. post-dose blood samples of 3.5 mL each will be drawn at During IV infusion:Blood samples(1 x 3.5 ml)will be collected at0.250,0.500,0.750 and 1 hr after start of IV. After completion of the IV
Post-dose blood samples(1 x 3.5 ml)collected at0.083,0.25 ,0.500,1.00,3.00,5.00,8.00,24.00,48.00,96.00,168.00,240.00,336.00hr after completion of the IV. 
 
Secondary Outcome  
Outcome  TimePoints 
To monitor the adverse events and to ensure the safety of Patient  N/A 
 
Target Sample Size   Total Sample Size="48"
Sample Size from India="48" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   N/A 
Date of First Enrollment (India)   01/08/2013 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Not Applicable 
Recruitment Status of Trial (India)  Other (Terminated) 
Publication Details    
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary
Modification(s)  

This study is a multicenter, open label, randomized, balanced, two treatment, two period, two sequence, two way crossover, single dose, bioequivalence study of Doxorubicin Hydrochloride  Liposome Injection  (2mg/mL) (10mL)  of Onco Therapies Limited, Bangalore, India with  Doxil®Doxorubicin HCl liposome injection, 20mg in 10mL (2 mg/mL)  Manufactured by: Ben Venue Laboratories, Inc., Bedford, OH 44146 manufactures forJanssen  Products, LP Horsham, PA 19044 administered in female patients with ovarian cancer whose disease has progressed or recurred after platinum based chemotherapy under fed condition

Treatments will be allocated to patient by carrying out randomization using statistical techniques. Total number of subjects will be enrolled in to the study in order to complete the study with 48 subjects

The dose of doxorubicin HCl for individual patient will be calculated according to body surface area and same dose will be administered in both the periods.There will be a washout period of 28 days, between two successive dosing (two successive periods). 

Patients will be randomized to receive intravenous infusion of either test or reference product of doxorubicin hydrochloride injection 2mg/mL (10mL) by IV infusion after dilution over 60 minutes period as per randomization schedule.

Total expected duration of the study will be of at least 43 days from the first day of IMP administration in period I till the end of study sample collection in period II. 

All the Adverse events and serious adverse events will be recorded from the signing of the  Informed consent form till 30 days after the last dose of study drug administration. 

The study was not initiated and no subjects were enrolled hence to update and close the CTRI from the sponsors end the study status was updated to terminated. 

 
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