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CTRI Number  CTRI/2017/12/010926 [Registered on: 20/12/2017] Trial Registered Retrospectively
Last Modified On: 21/11/2019
Post Graduate Thesis  No 
Type of Trial  BA/BE 
Type of Study    
Study Design  Randomized, Crossover Trial 
Public Title of Study   Clinical Bioequivalence Study of Doxorubicin Hydrochloride Liposome Injection (IV) 2 mg/ml (50mg/m2) in Ovarian Cancer Patients whose disease has progressed or recurred after platinum-based chemotherapy under fasting conditions 
Scientific Title of Study   A Multicentric, Open-label, Randomized, Two Treatment, Two Sequence, Cross Over, Clinical Bioequivalence Study of Doxorubicin Hydrochloride Liposome Injection (IV) 2 mg/ml (50mg/m2) of Auromedics Pharma LLC, USA (Test) With Doxorubicin Hydrochloride Liposome Injection (IV) 2 mg/ml (50mg/m2) of Sun Pharmaceutical Industries, Inc, USA (Reference) in Ovarian Cancer Patients whose disease has progressed or recurred after platinum-based chemotherapy under fasting conditions 
Trial Acronym  CR150-16 
Secondary IDs if Any  
Secondary ID  Identifier 
CR150-16, Version 1.0 Amendment-03 Dated 03.11.2017  DCGI 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Subhra Lahiri 
Designation  Associate Vice President 
Affiliation  AXIS Clinicals Ltd 
Address  1-121/1
Miyapur
Hyderabad
ANDHRA PRADESH
500049
India 
Phone  914040408064  
Fax  914040408060  
Email  Subhra.L@axisclinicals.com  
 
Details of Contact Person
Scientific Query  
Name  Dr Subhra Lahiri 
Designation  Associate Vice President 
Affiliation  AXIS Clinicals Ltd 
Address  1-121/1
Miyapur
Hyderabad
ANDHRA PRADESH
500049
India 
Phone  914040408064  
Fax  914040408060  
Email  Subhra.L@axisclinicals.com  
 
Details of Contact Person
Public Query  
Name  Dr Subhra Lahiri 
Designation  Associate Vice President 
Affiliation  AXIS Clinicals Ltd 
Address  1-121/1
Miyapur
Hyderabad
ANDHRA PRADESH
500049
India 
Phone  914040408064  
Fax  914040408060  
Email  Subhra.L@axisclinicals.com  
 
Source of Monetary or Material Support  
APL Research Center Aurobindo Pharma Limited Survey No -313, Bachupally Village, Qutubullapur Mandal, Hyderabad  
 
Primary Sponsor  
Name  APL Research Center 
Address  Aurobindo Pharma Limited Survey No -313, Bachupally Village, Qutubullapur Mandal, Hyderabad -500 090, India Telphone number 914023040262, Fax Number 914023012932  
Type of Sponsor  Pharmaceutical industry-Indian 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study
Modification(s)  
No of Sites = 15  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Poulome Mukherjee  Cachar Cancer Hospital and Research Centre  Meherpur, Silchar-788015
Cachar
ASSAM 		 8281392489
03842240608
poulome.mukherjee@cacharcancerhospital.org 
Dr Gopichand M  City Cancer Centre  33-25-33 CH Venkatakrishnayya street Suryaraopet, vijaywada-520002
Krishna
ANDHRA PRADESH 		 988526059

mgopichand@yahoo.com 
Dr K Velavan  Erode Cancer Centre  1/393 Velavan Nagar Perundurai road Thindal Erode -638012
Erode
TAMIL NADU 		 9842334222

kvels@rediffmail.com 
Dr C Sairam  Global Hospitals  6-1-1070/1 to 4 lakadikapul Hyderabad-500004
Hyderabad
ANDHRA PRADESH 		 9849032198

drcsairam@gmail.com 
Dr G Raja  Hindu Mission Hospital  No:103 GST road west Tambaram Chennai-600045
Chennai
TAMIL NADU 		 9841107677

rajaresearch17@gmail.com 
Dr Sathya M  K R Hospital-MMCRI   Irwin Road Mysore-570001
Dakshina Kannada
KARNATAKA 		 9901040001

sathya_678@hotmail.com 
Dr Rohan Bhise  KLE s Dr Prabhakar Kore Hospital & MRC  NH 4A Belgaum Nehru nagar Belagavi 590010
Belgaum
KARNATAKA 		 9844345999

rohanbhise30@gmail.com 
Dr Ranganatha Rao Srikanth  MNJ Institute of Oncology and regional cancer Centre  Red Hills Hyderabad-500004
Hyderabad
ANDHRA PRADESH 		 9849009958
04023314063
srikanthsapthagiri@yahoo.com 
Dr M Prabagar  N G Hospital Pvt Ltd  577 Trichy Road Singanallur Coimbatore 641005
Coimbatore
TAMIL NADU 		 9443681554

prabagardr@gmail.com 
Dr P N Sathiya Moorthy  Noble Hospital  No.04 - Audiappa street Purasaiwakkamchennai-600084
Chennai
TAMIL NADU 		 9444221535

sathiyamoorthypn@gmail.com 
Dr Rachan Shetty  Omega Hospital  Mahaveer Circle kankanady Mangalore-575002
Dakshina Kannada
KARNATAKA 		 9008753317

drrachanshetty.medoncology@gmail.com 
Dr Aniket Thoke  Sanjeevani CBCC USA Cancer Hospital  Infront of Jain Mandir, Dawada Colony, Pachpedi Naka 492001
Raipur
CHHATTISGARH 		 9752925741
07714013120
drthoke@gmail.com 
Dr Shailesh A Bondarde  Shatabdi Super speciality Hospital  Suyojit City Center Opp Mahamarg Bus Stand Mumbai Naka Nashik – 422005
Nashik
MAHARASHTRA 		 9822012427

shaileshbondarde1971@gmail.com 
Dr Rajeev A G  The Radiant Institute  A-1 Block Vijayanagar 3rd Stage, Mysore-570017
Mysore
KARNATAKA 		 9844345999

drrajeevag@gmail.com 
Dr Ankit Patel  Unique Hospital-Multispecialty and research Institute  Opp. Kiran Motor Char Rasta-Sosyo circle lane Off. Ring road Surat-395002
Surat
GUJARAT 		 9825404202

drankitoncologist@gmail.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 15  
Name of Committee  Approval Status 
Cachar Cancer Hospital and Research Centre Institutional Review Board  Approved 
Ethics Committee Unique Hospital  Approved 
Institution Ethics Committe NG Hospital Pvt Ltd  Approved 
Institutional Ethics Committee City Cancer centre   Approved 
Institutional Ethics Committee Erode cancer centre   Approved 
Institutional Ethics Committee Gleneagles Global Hospitals   Approved 
Institutional Ethics Committee Hindu Mission Hospital   Approved 
Institutional Ethics Committee KLE university Nehru   Approved 
Institutional Ethics committee MNJ Institute of Onclogy and Regional Cancer Centre  Approved 
Institutional Ethics Committee Mysore medical college and research Institute   Approved 
Institutional Ethics Committee Noble Hospital   Approved 
Institutional Ethics Committee The Radiant Institute  Approved 
Omega Ethical Committee  Approved 
Sanjeevani Cancer Hospital Institutional Ethics Committee  Approved 
Shatabdi Hospital ethics Committee   Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Ovarian Cancer Patients whose disease has progressed or recurred after platinum based chemotherapy under fasting conditions,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Doxorubicin Hydrochloride Liposome Injection (IV) 2 mg/ml (50mg/m2) of Auromedics Pharma LLC, USA  The study will consist of two periods. Eligible patients will be dosed with Doxorubicin HCl liposome injection (either Test or Reference product based on Randomization schedule) on Day 1 and day 29 
Comparator Agent  Doxorubicin Hydrochloride Liposome Injection (IV) 2 mg/ml (50mg/m2) of Sun Pharmaceutical Industries, Inc, USA  The study will consist of two periods. Eligible patients will be dosed with Doxorubicin HCl liposome injection (either Test or Reference product based on Randomization schedule) on Day 1 and day 29 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  75.00 Year(s)
Gender  Female 
Details  1. Patients must be above 18 and below 75 years of age
2. Life expectancy of greater than or equal to 12 weeks.
3. Histologically or cytologically confirmed diagnosis of epithelial ovarian carcinoma (FIGO Stage II to IV) and who are already receiving or scheduled to start therapy with the Liposomal Doxorubicin.
4. One or 2 previous chemotherapy regimens for advanced ovarian cancer. At least one of these regimens must have contained a platinum agent.
5. Patients who are either platinum-resistant (relapse less than 6 months after completing a platinum-containing regimen) or platinum sensitive (relapse above or equal to 6 months after platinum-containing regimen) are eligible.
6. Cytological or imaging confirmation of ovarian cancer recurrence after platinum therapy.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
8. Normal left ventricular ejection fraction (LVEF greater than 50%) according to institutional standards. Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of a minor surgery (with the exception of port-a-cath placement); at least 4 weeks must have elapsed from the time of a major surgery.
9. Laboratory values as follows:
• Absolute neutrophil count (ANC) greter than or equal to 1500/µL.
• Hemoglobin (Hb)greater than or equal to 9g/dL. Patients may not have received RBC transfusions within 7 days of screening assessment.
• Platelets greated than or equal to 100,000/ µL.
• AST or ALT must be less than 2.5 x ULN (concomitant elevations in bilirubin and AST/ALT greater than 1.0 x ULN are not permitted).
• Total bilirubin less than 1.2 x the institutional ULN (if Gilberts syndrome, direct bilirubin less than or equal to 1.2 x ULN).
• International normalized ratio (INR) less than or equal to 1.2 and activated partial thromboplastin time (aPTT) less than or equal to 1.2 x the ULN (except for patients receiving anti-coagulation therapy).
• Creatinine greater than or equal 1.5 x ULN.
10. Patients and/ or LAR must be able to understand the investigational nature of this study and give written informed consent prior to study entry.
11. Women of childbearing potential must agree to use adequate contraception prior to study entry, for the duration of study participation and for 180 days following completion of therapy. Women of childbearing potential must have a negative serum pregnancy test within 20 days prior to initiation of treatment.
12. Females must use acceptable and effective methods of contraception such as the following:
• Tubal sterilization (tubal ligation performed more than one month before Study Day 1; transcervical tubal occlusion procedure performed more than six months before Study Day 1)
• Intrauterine Device (IUD)
• Progestin Implant (i.e. Implanon or its equivalent)
• Progestin injection or progestin oral contraceptive pill + one barrier method (cervical cap, diaphragm, contraceptive sponge, or vaginal spermicide + a male or female condom)
• Two barrier methods used together (cervical cap, diaphragm, contraceptive sponge, or vaginal spermicide + a male or female condom)
• Absolute sexual abstinence (no sexual intercourse or genital contact with a male partner)
13. Post-menopausal women must be amenorrheic for at least 12 months be considered of non-childbearing potential.
 
 
ExclusionCriteria 
Details  1. Patients who have a history of hypersensitivity reactions to a conventional formulation of doxorubicin hydrochloride or the components.
2. Prior doxorubicin exposure that would result in a total lifetime exposure of 550 mg/m2 or more after four cycles of treatment.
3. Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, P. carinii or other microorganism if under treatment with myelotoxic drugs.
4. Patients with brain metastases.
5. Patients with known endobronchial lesions and/or lesions infiltrating major pulmonary vessels.
6. Patients with significantly impaired hepatic OR renal function
7. Patients with hemoptysis within 6 weeks of first dose of study drug.
8. Patients who are pregnant or breast feeding.
9. Impaired cardiac function including any of the following conditions within the past 6 months:
• NYHA Class II, III or IV heart failure.
• QTc prolongation or other significant ECG abnormalities.
• Myocardial infarction or unstable angina.
• Coronary artery bypass graft surgery.
• Symptomatic peripheral vascular disease.
• History of sustained ventricular tachycardia.
10. Patients who have taken any potent CYP3A4 inhibitors within or equal to 14 days prior to enrollment including but not limited to:
ketoconazole, itraconazole, troleandomycin, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, amprenavir, nefazodone, fluvoxamine, diltiazem, verapamil, mibefradil, cimetidine, cyclosporine, and grapefruit juice.
11. Uncontrolled hypertension [systolic blood pressure (BP)greater than 180 or diastolic BP greater than 100mm Hg] or uncontrolled cardiac arrhythmias (Patients with hypertension controlled by antihypertensive therapies are eligible.)
12. History of cerebrovascular accident (CVA), or venous thrombosis within 12 weeks (Patients with previous history of venous thrombosis on a stable dose of anticoagulation are allowed).
13. Concurrent severe, intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit safety and compliance with study requirements.
14. Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter drug absorption (e.g., active inflammatory bowel disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or significant small bowel resection).
15. Mental condition that would prevent patient comprehension of the nature of, and risk associated with the study.
16. Use of any non-approved or investigational agent within or equal to 30 days prior to Randomization. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
17. Past or current history of neoplasm other than the entry diagnosis with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other cancers cured by local therapy alone and a disease free survival ≥ 5 years.
18. A positive hepatitis screen including hepatitis B surface antigen, HCV and HIV antibodies.
19. Donation / loss of blood (without replenishment) (1 unit or 350 mL) within 90 days prior to receiving the first dose of study medicine.
20. Patients experience Hand foot syndrome, hematologic toxicities and Stomatitis or any other adverse drug reactions, abnormal laboratory parameters and abnormal vital signs that require dose modifications.
21. Females of child bearing potential unwilling to use acceptable contraception throughout the trial and for 6 months after the last dose of study drug
 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Cmax: Maximum measured plasma concentration over the time span specified.
AUC0-t: The area under the plasma concentration versus time curve, from time 0 to the last measurable concentration, as calculated by the linear trapezoidal method.
AUC0-∞: The area under the plasma concentration versus time curve from time 0 to time infinity. AUC0-∞ is calculated as the sum of the AUC0-t plus the ratio of the last measurable plasma concentration (Ct) to the elimination rate constant Kel.
 		 Day 1, predose and at .25, .50, .75, 1 hour (±5 mins) and at 1.17,1.25,1.5, 2,2.5,3,5,7,9,13,25 hrs post dose. Ambulatory samples at 49 (Day 3), 97 (5), 169 (8), 241 (11), and 337 (15), 504 hours (Day 21)
Day 29: pre-dose (0) and at .25, .50, .75, 1 hour (±5 mins) and at 1.17,1.25,1.5, 2,2.5,3,5,7,9,13,25 hrs post dose. Ambulatory samples at 49 (Day 31), 97 (33), 169 (36), 241 (39),337 ( 43), 504 hours (Day 49)

 
 
Secondary Outcome  
Outcome  TimePoints 
Safety and tolerability as assessed by reported adverse events, laboratory and clinical investigations  All visits 
Tmax
Kel
T1/2
AUC% extrapolation 		 As per primary outcome 
 
Target Sample Size   Total Sample Size="60"
Sample Size from India="60" 
Final Enrollment numbers achieved (Total)= "0"
Final Enrollment numbers achieved (India)="71" 
Phase of Trial   N/A 
Date of First Enrollment (India)
Modification(s)  		 23/01/2018 
Date of Study Completion (India) 03/09/2018 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Date Missing 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Not Applicable 
Recruitment Status of Trial (India)  Completed 
Publication Details   Not applicable 
Individual Participant Data (IPD) Sharing Statement

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

Brief Summary  

This is a multicentre study and the primary objective of this study is To determine clinical bioequivalence (compare the rate and extent of absorption) of Doxorubicin Hydrochloride Liposome Injection (IV) 2 mg/mL (50 mg/m2) of Auromedics Pharma LLC, USA (Test) with Doxorubicin Hydrochloride Liposome Injection (IV) 2 mg/mL (50mg/m2) of Sun Pharmaceutical Industries, Inc, USA (Reference) in Ovarian Cancer Patients whose disease has progressed or recurred after platinum-based chemotherapy under fasting conditions.

The secondary objective of this study is to assess safety and tolerability of Doxorubicin Hydrochloride Liposome Injection (IV) 2 mg/mL (50 mg/m2)  as assessed by reported adverse events, laboratory and clinical investigations and vital signs. 
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