CTRI/2015/10/006241 [Registered on: 06/10/2015] Trial Registered Prospectively
Last Modified On:
28/12/2018
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Bioequivalence study of
Doxorubicin Hydrochloride (Pegylated liposomal concentrate for solution for infusion 20 mg/10mL (2 mg/ml) in advanced ovarian cancer.
Scientific Title of Study
A multicenter, open label, randomized, two-treatment, two-period,two-sequence, single dose, cross-over bioequivalence study of
Doxorubicin Hydrochloride (Pegylated liposomal concentrate for solution for infusion 20 mg/10mL (2 mg/ml) of Dr. Reddy’s Laboratories Ltd, India, with that of Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal) concentrate for
solution for infusion (20 mg/10mL)] of Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium in advanced
ovarian cancer or metastatic breast cancer patients under fed condition.
Trial Acronym
15-VIN-616
Secondary IDs if Any
Secondary ID
Identifier
15-VIN-616 Version 01 05 Aug 2015
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Ashoka Kumar Singh
Designation
Head Of the Department - Clinical Operations
Affiliation
Veeda Clinical Research Pvt. Ltd
Address
Shivalik Plaza-A, Near IIM, Ambawadi, Ahmedabad.
Ahmadabad GUJARAT 380015 India
Phone
079-30013000
Fax
Email
ashoka.singh@veedacr.com
Details of Contact Person Scientific Query
Name
Dr Ashoka Kumar Singh
Designation
Head Of the Department - Clinical Operations
Affiliation
Veeda Clinical Research Pvt. Ltd
Address
Shivalik Plaza-A, Near IIM, Ambawadi, Ahmedabad.
Ahmadabad GUJARAT 380015 India
Phone
079-30013000
Fax
Email
ashoka.singh@veedacr.com
Details of Contact Person Public Query
Name
Dr Ashoka Kumar Singh
Designation
Head Of the Department - Clinical Operations
Affiliation
Veeda Clinical Research Pvt. Ltd
Address
Shivalik Plaza-A, Near IIM, Ambawadi, Ahmedabad.
Ahmadabad GUJARAT 380015 India
Phone
079-30013000
Fax
Email
ashoka.singh@veedacr.com
Source of Monetary or Material Support
Dr. Reddy’s Laboratories, India.
Primary Sponsor
Name
Dr Reddys Laboratories Limited
Address
Integrated Product Development, Bachupally, Quthubullapur Mandal, Survey No:42, 45 and 46, R R Dist- 500 090,Telangana, India.
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
Veeda Clinical Research Pvt Ltd
Shivalik Plaza, Near I.I.M., Ambawadi, Ahmedabad–380 015, India
Countries of Recruitment
India
Sites of Study
No of Sites = 17
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Patel Ghanshyam Nanubhai
Apple Hospital
Department of Oncology, Apple Hospital, Udhna Darwaja, Ring Road, Surat 395002, Gujarat Surat GUJARAT
9376913131
gnonco@gmail.com
Dr Koushik Chatterjee
B. P. Poddar Hospital & Medical Research Ltd.
Department of Gynecologic Oncology, B. P. Poddar Hospital & Medical Research Ltd.,
71/1, Humayun Kabir Sarani, Block-G
New Alipore, Kolkatta - 700053, West Bengal Kolkata WEST BENGAL
9874357580
drkoushik.chatterjee@gmail.com
Dr Jaiprakash Baraskar
Baraskar Hospital and Research Centre
Department of Oncology, Baraskar Hospital and Research Centre, 276, Crystal Plaza, Central Bazar Road Ramdaspeth, Nagpur-440010, Maharashtra Nagpur MAHARASHTRA
9422108822
jpcancercare@yahoo.co.in
Dr Ranajit Kumar Mandal
Chittaranjan National Cancer Institute
Department of Gynecologic Oncology, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkatta 700026, West Bengal Kolkata WEST BENGAL
9831002078
kranajitmandal@yahoo.co.in
Dr Gururaj Deshpande
City Cancer Centre
Department of Oncology, City Cancer Centre,33-25-33, Ch. Venkata Krishnayya Street,
Suryarao pet, Vijayawada-520002
Andhra Pradesh Krishna ANDHRA PRADESH
9603548495
drgururajdeshpande@gmail.com
Dr Rajnish Vasant Nagarkar
Curie Manavata Cancer Centre
Department of Oncology, Curie Manavata Cancer Centre, Opp: Mahamarg Bus Stand, Mumbai Naka, Nashik–422 004, Maharashtra. Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr Arun Seshachalam
Dr. GVN Cancer Institute (a Unit of GVN Hospital)
Department of Oncology, Dr. GVN Cancer Institute (a Unit of GVN Hospital), No.46, Singarathope, Trichirappalli-620008, Tamilnadu Tiruchirappalli TAMIL NADU
9786220191
arunonco@gmail.com
Dr K Velavan
Erode Cancer Centre
Department of Oncology, Erode Cancer Centre, Velavan Nagar, (Near Chinthamani Petrol Bunk), Perundurai Road,
Erode – 638012, Tamilnadu. Erode TAMIL NADU
9842334222
kvels@rediffmail.com
Dr Shibashish Bhattacharyya
Health Point Multispeciality Hospital
Department of Oncology, Health Point Multispeciality Hospital, 21,Prannath Pandit Street,(Opposite Lansdown Padmapukur), Kolkata-700025, West Bengal Kolkata WEST BENGAL
9051837235
shibashishbhattacharya@ymail.com
Dr Kartikeya Jain
Kailash Cancer Hospital & Research Centre
Department of Oncology, Kailash Cancer Hospital & Research Centre, Muni Seva Ashram, Goraj – 391760, Vaghodia, Vadodara, Gujarat Ahmadabad GUJARAT
9427432642
kartikeya.jain@greenashram.org
Dr Neve Rakesh Suresh
Maharashtra Medical Foundation Joshi Hospital
Department of Oncology, Maharashtra Medical Foundation Joshi Hospital, 778, Opposite Kamala Nehru Park, Pune-411004, Maharashtra. Pune MAHARASHTRA
9225510913
drrakeshn@gmail.com
Dr Sushil Mandhaniya
Mandhaniya Cancer Hospital & Research Institute
Department of Oncology, Mandhaniya Cancer Hospital & Research Institute,
A-101, First Floor, Neeti Gaurav Complex,
20 Central Bazar Road,
Adjacent to Hotel Centre Point, Nagpur – 440010, Maharashtra Nagpur MAHARASHTRA
9673812221
sushilnagpur001@yahoo.co.in
Dr Sangeeta Jiwatani
Mangal Anand Hospital
Department of Gynecology and Oncology, Mangal Anand Hospital, 48 , Swastik Park, Sion - Trombay Road,
Chembur, Mumbai – 400071,
Maharashtra Mumbai MAHARASHTRA
9494295023
sangeetajiwatani@hotmail.com
Dr Rajesh Makadia
Shree Giriraj Multispeciality Hospital
Department of Gynecologic Oncology, Shree Giriraj Multispeciality Hospital, 150 Feet Ring Road,
27- Navjot Park Main Road,
Amin Marg Cross Road,
Rajkot- 360005, Gujarat Rajkot GUJARAT
9824255668
makadiarajesh@rocketmail.com
Dr Shobha Krishnappa
Srinivasam Cancer Care Hospitals India Pvt. Ltd.,
Department of Oncology, Srinivasam Cancer Care Hospitals India Pvt. Ltd., No. 236/1, Vijayashree layout, Arekere, Bannarghatta Main Road, Bangalore-560076, Karnataka. Bangalore KARNATAKA
9448055949
drshoba2010@gmail.com
Dr Shamsuddin Virani
Unique Hospital-Multispecialty & Research Institute
Department of Gynecology and Oncology, Unique Hospital-Multispecialty & Research Institute, Opp. Kiran Motor, Nr. Canal, Civil Hospital Char Rasta- Sosyo Circle Lane, Off ring road, Surat - 395002, Gujarat Surat GUJARAT
9879855522
drsjvirani@gmail.com
Dr M Prabhagar
VGM Cancer Care (A unit of VGM Hospital),
Department of Oncology, VGM Cancer Care (A unit of VGM Hospital), #2100, Trichy Road, Rajalakshmi Mills Stop, Coimbatore - 641005, Tamilnadu Coimbatore TAMIL NADU
(1) ICD-10 Condition: C569||Malignant neoplasm of unspecifiedovary, (2) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Caelyx® 2mg/mL
[Doxorubicin Hydrochloride (Pegylated Liposomal) concentrate for solution for infusion (20 mg/10mL)].
(Period I): Subjects will receive 50mg/m2 dose of Doxorubicin Hydrochloride (Pegylated liposomal concentrate for solution for infusion (either test or reference product) on the first day of the chemotherapy cycle under fed condition.
(Period II): Subjects will receive 50mg/m2 dose of Doxorubicin Hydrochloride (Pegylated liposomal) concentrate for solution for infusion (either test or reference product) on the first day of the next chemotherapy cycle under fed condition.
Intervention
Doxorubicin Hydrochloride (Pegylated liposomal) concentrate for solution for infusion 20 mg/10mL (2 mg/ml)
(Period I): Subjects will receive 50mg/m2 dose of Doxorubicin Hydrochloride (Pegylated liposomal concentrate for solution for infusion (either test or reference product) on the first day of the chemotherapy cycle under fed condition. (Period II): Subjects will receive 50mg/m2 dose of Doxorubicin Hydrochloride (Pegylated liposomal) concentrate for solution for infusion (either test or reference product) on the first day of the next chemotherapy cycle under fed condition
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Female
Details
1. Females of Indian Nationality, between 18-65 years of age (both inclusive).
2. Ability to understand and provide written informed consent prior to participation in the study.
3. Patients with advanced ovarian cancer requiring Doxorubicin and who have failed a first-line platinum-based chemotherapy regimen. Or As monotherapy for patients with metastatic breast cancer.
4. Cardiac function (left ventricular ejection fraction [LVEF] ≥50%.
5. Patient should have recovered from any toxic effects of previous chemotherapy as judged by the Investigator.
6. Patients with life expectancy of at least 3 months.
7. Able to comply with study requirement in opinion of Principal Investigator.
8. Adequate Hematopoietic, Renal and Liver function defined as the following:
Bone marrow function:
ANC ≥ 1500/mm3
Platelet count ≥ 100,000/mm3
Haemoglobin ≥ 9.0 g/dl
Renal function:
S. Creatinine < 1.5 x upper limit of normal ULN)
Hepatic function:
AST and ALT ≤ 2.5 × ULN (≤ 4 × ULN for liver metastasis)
Alkaline phosphatase < 2 x ULN (≤ 5 × ULN for bone metastasis).
Total Bilirubin ≤ 1.5 × ULN
9. Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of minor surgery; at least 4 weeks must have elapsed from the time of major surgery.
10. Sexually active women, unless surgically sterile (at least 6 months prior to Study drug administration) or postmenopausal for at least 12
consecutive months, must have negative pregnancy test at screening as well as prior to check-in and must agree to 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 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.
ExclusionCriteria
Details
1. Patients who are pregnant or breast feeding.
2. Patients with an ECOG (Eastern Cooperative Oncology group)Performance Status Score > 3.
3. If total cumulative dose of Doxorubicin HCl approaches 450 mg/m2
4. Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, P.carinii or other microorganism if under treatment with myelotoxic drugs.
5. Any other clinically significant liver or kidney disorders other than mentioned in the selection criteria.
6. Impaired cardiac function including any of the following conditions within past 6 months:
a. Unstable angina
b. QTc prolongation or other significant ECG abnormalities.
c. Coronary artery bypass graft surgery.
d. Symptomatic peripheral vascular disease.
e. Myocardial infarction
f. NYHA class II-IV heart failure
g. Severe uncontrolled ventricular arrhythmias
h. Clinically significant pericardial disease
i. Electrocardiographic evidence of acute ischemic or active conduction system abnormalities.
j. Patients with evidence of abnormal cardiac conduction (e.g., bundle branch block or heart block) are eligible if their disease has been stable for the past six months.
k. Severe uncontrolled arrhythmias.
7. History of hypersensitivity reactions attributed to a conventional formulation of Doxorubicin Hydrochloride or the components of Caelyx®.
8. Use of any recreational drugs or history of drug addiction.
9. Known brain metastasis.
10. Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by NCI criteria.
11. Other serious illness or medical condition that would prohibit the understanding and giving of informed consent.
12. A positive hepatitis screen including hepatitis B surface antigen, HCV and HAV antibodies.
13. A positive test result for HIV antibody and/or syphilis.
14. The receipt of an investigational product, or participation in a drug research study within a period of 90 days prior to the first dose of
investigational Product.
15. Any other condition that, in the investigator judgment, might increase the risk to the patient or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
16. Abnormal baseline findings considered by the investigator to indicate conditions that might affect study endpoints.
17. Current or relevant previous history of serious, severe or unstable (acute or progressive) physical or psychiatric illness, any medical disorder that may require treatment or make the patient unlikely to fully complete the
study, or any condition that presents undue risk from the study medication or procedures.
18. History of donation of blood/loss of blood (without replenishment) (1 unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product in the study.
19. Uncontrolled hypertension (systolic blood pressure [BP] >180 or diastolic BP >100mm Hg) or uncontrolled cardiac arrhythmias (Patients with hypertension controlled by antihypertensive therapies are eligible).
20. History of cerebrovascular accident (CVA), MI within 6 months or venous thrombosis within 12 weeks. (Patients with previous history of venous thrombosis on a stable dose of anticoagulation are allowed).
21. Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
22. 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.
23. Patients who have taken any potent CYP3A4 inhibitors/inducers ≤ 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.
Method of Generating Random Sequence
Method of Concealment
Blinding/Masking
Primary Outcome
Outcome
TimePoints
To assess the bioequivalence of the Test Produc (Doxorubicin Hydrochloride (Pegylated liposomal)concentrate for solution for
infusion 20 mg/10mL (2mg/mL)) relative to that of Reference Product (Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal)
concentrate for solution for infusion (20 mg/10mL)]) in advanced ovarian cancer patients who have failed a first-line platinum based chemotherapy regimen or patients with metastatic breast cancer.
To assess the bioequivalence of the Test Produc (Doxorubicin Hydrochloride (Pegylated liposomal)concentrate for solution for
infusion 20 mg/10mL (2mg/mL)) relative to that of Reference Product (Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal)
concentrate for solution for infusion (20 mg/10mL)]) in advanced ovarian cancer patients who have failed a first-line platinum based chemotherapy regimen or patients with metastatic breast cancer.
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events and to ensure the safety of the patients.
NA
Target Sample Size
Total Sample Size="50" Sample Size from India="50" Final Enrollment numbers achieved (Total)= "65" Final Enrollment numbers achieved (India)="65"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is a multicenter, open label, randomized, two-treatment, two-period, two-sequence, single dose, cross-over bioequivalence study of Doxorubicin Hydrochloride (Pegylated liposomal) concentrate for solution for infusion 20 mg/10mL (2 mg/ml) of Dr. Reddy’s Laboratories Ltd, India, with that of Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal) concentrate for solution for infusion (20 mg/10mL)] of Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium in advanced ovarian cancer or metastatic breast cancer patients under fed condition.
In Period-I Subjects will receive 50mg/m2 dose of Doxorubicin Hydrochloride (Pegylated liposomal) concentrate for solution for infusion (either test or reference product) on the first day of the chemotherapy cycle under fed condition. In Period-II Subjects will receive 50mg/m2 dose of Doxorubicin Hydrochloride (Pegylated liposomal) concentrate for solution for infusion (either test or reference product) on the first day of the next chemotherapy cycle under fed condition. The dose of Doxorubicin Hydrochloride for individual subject will be calculated according to body surface area (Calculated by Dubois formula).
A total of 21 blood samples will be collected during each period. The pre infusion blood sample of 6 mL (00.0) will be collected within one hour prior to start of infusion. The post-dose blood samples of 6 mL each will be drawn at 0.25, 0.50, 0.75, 1.00 (i.e. at end of infusion), 1.25, 1.50, 2.00, 3.00, 4.00, 6.00, 12.00, 24.00, 48.00, 72.00, 120.00, 168.00, 216.00, 264.00, 312.00 and 360.00 hours after start time of intravenous Infusion.