CTRI/2020/08/027445 [Registered on: 28/08/2020] Trial Registered Prospectively
Last Modified On:
22/08/2022
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 concentrate for solution for infusion 20 mg/10 ml in patients with advanced ovarian cancer and/or metastatic breast cancer.
Scientific Title of Study
A multicenter, open label, balanced, 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 and/or metastatic breast cancer patients under fed condition.
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sumit Arora
Designation
Vice President Clinical Operations
Affiliation
Veeda Clinical Research Pvt, Ltd.
Address
Veeda Clinical Research Pvt. Ltd Shivalik Plaza, Near I.I.M.
Ambawadi Ahmedabad, Gujarat 380 015 India
Ahmadabad GUJARAT 380015 India
Phone
7930013000
Fax
7930013010
Email
Sumit.arora@veedacr.com
Details of Contact Person Scientific Query
Name
Dr Ravi Alamchandani
Designation
Dy. General Manager
Affiliation
Veeda Clinical Research Pvt, Ltd.
Address
Veeda Clinical Research Pvt. Ltd Shivalik Plaza, Near I.I.M.
Ambawadi Ahmedabad, Gujarat 380 015 India
Ahmadabad GUJARAT 380015 India
Phone
7930013000
Fax
7930013010
Email
Ravi.A1950@veedacr.com
Details of Contact Person Public Query
Name
Dr Ravi Alamchandani
Designation
Dy. General Manager
Affiliation
Veeda Clinical Research Pvt, Ltd.
Address
Veeda Clinical Research Pvt. Ltd Shivalik Plaza, Near I.I.M.
Ambawadi Ahmedabad, Gujarat 380 015 India
Ahmadabad GUJARAT 380015 India
Phone
7930013000
Fax
7930013010
Email
Ravi.A1950@veedacr.com
Source of Monetary or Material Support
Dr. Reddy s Laboratories Ltd.
Integrated Product Development,
Bachupally, Quthubullapur Mandal,
Survey No 42, 45 and 46,
R R Dist 500 090 Telangana India
Primary Sponsor
Name
DrReddys Laboratories
Address
Dr. Reddy s Laboratories Ltd.
Integrated Product Development,
Bachupally, Quthubullapur Mandal,
Survey No 42, 45 and 46,
R R Dist 500 090 Telangana India
Dhadiwal Hospital In Coaliation with Shreeji HealthCare
opp. New CBS, Trimbak Road, Nashik 422002, Maharashtra Nashik MAHARASHTRA
9595160424
mukeshchandre@gmail.com
Dr Subeera Khan
Government Medical College & Hospital
Hanuman Nagar, Ajni Rd, Medical Chowk, Ajni, Nagpur-440003, Maharashtra, India. Nagpur MAHARASHTRA
9096073358
subeera.k@gmail.com
Dr L P Bhaskar Bhuvan
HCG Cancer Centre
HCG Cancer Centre (A unit of Health Care Global Enterprises Ltd), Plot No. 10, Survey No. 13P, APIIC Health City, Arilova, Chinnagadili, Mudosarlova Road Visakhapatnam - 530040, Andhra Pradesh, India Visakhapatnam ANDHRA PRADESH
Opp Mahamarg Bus Stand, Mumbai Naka, Nashik - 422002, Maharashtra Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr Kartikeya Jain
Himalaya Cancer Hospital & Research Institute
Himalaya Cancer Hospital & Research Institute, Opp Railway Station, Vinod Baugh, Jetalpur Road, Alkapuri, Vadodara - 390020, Gujarat Dohad GUJARAT
9427432642
divahoclinic@gmail.com
Dr Prakash SS
K R Hospital,
Dept. of Surgical Oncology, Clinical Research Room,
Next to NSB 12, 2nd Floor, New Surgical Block,
K.R. Hospital,
Mysore Medical College & Research Institute, Mysore-570001, Karnataka Mysore KARNATAKA
Institutional Ethics Committee Government Medical college
Approved
Institutional Ethics committee HCG Cancer hospital Vizag
Approved
Institutional Ethics Committee Mysore medical college & research institute
Approved
Institutional Ethics Commmittee, KLE University
Approved
Kingsway Ethics Committee
Approved
Kiran Hospital Ethics Committee
Approved
Kolhapur Cancer Centre Institutional Ethics Committee
Approved
Manavata Clinical Research Institute Ethics Committee
Approved
Medstar Speciality Hospital Ethics Committee
Approved
MNJ Institute of Oncology & Regional Cancer Centre Ethics Committee
Approved
MNJ Institute of Oncology & Regional Cancer Centre Ethics Committee
Approved
Noble Hospital Institutional Ethics commttiee
Approved
Shree Institutional Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site, (2) ICD-10 Condition: C569||Malignant neoplasm of unspecifiedovary,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal) concentrate for solution for infusion (20 mg/10mL)] of Janssen-Cilag International NV
Single dose of Doxorubicin Hydrochloride as per randomization schedule
Intervention
Doxorubicin Hydrochloride (Pegylated liposomal) concentrate for solution for infusion 20 mg/10mLof Dr. Reddys Laboratories Ltd
Single dose of Doxorubicin Hydrochloride as per randomization schedule
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Female
Details
1. Females of age between 18-65 years (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. ECOG (Eastern Cooperative Oncology group) performance status of ≤ 2.
6. Patient should have recovered from any toxic effects of previous chemotherapy as judged by the Investigator.
7. Patients with life expectancy of at least 3 months.
8. Able to comply with study requirement in opinion of Principal Investigator.
9. Adequate Hematopoietic, Renal and Liver function defined as the following:
Body system Parameters
Bone marrow function ANC more than or equal to 1500/mm3
Platelet count more than or equal to 100,000/mm3
Haemoglobin ≥ 9.0 g/dl
Renal function Serum Creatinine ≤1.5 × upper limit of normal (ULN)
Hepatic function AST and ALT ≤3 × ULN (≤5 × ULN for liver metastasis)
Alkaline phosphatase ≤2.5 × ULN (≤5 × ULN for bone metastasis and ≤4 × ULN for liver metastasis).
Total Bilirubin ≤1.5 × ULN
10. 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.
11. Sexually active women, unless surgically sterile (with documented evidence of hysterectomy / bilateral salpingectomy / bilateral oophorectomy 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’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.
ExclusionCriteria
Details
1. Patients who are pregnant or breast feeding.
2. Prior doxorubicin exposure that would result in a total lifetime exposure of more than 450 mg/m2
3. Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, P.carinii or other microorganism if under treatment with myelotoxic drugs.
4. Any other clinically significant liver or kidney disorders other than mentioned in the selection criteria.
5. Impaired cardiac function including any of the following conditions within past 6 months:
a. Unstable angina
b. QTc prolongation (QTc > 470 millisecond) 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.
6. History of hypersensitivity reactions attributed to a conventional formulation of Doxorubicin Hydrochloride or the components of Doxorubicin Hydrochloride Liposome (Pegylated Liposomal).
7. Use of any recreational drugs or history of drug addiction.
8. Known brain metastasis.
9. Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by NCI criteria.
10. Other serious illness or medical condition that would prohibit the understanding and giving of informed consent.
11. A positive hepatitis screen including hepatitis B surface antigen, HCV and HAV antibodies.
12. A positive test result for HIV, antibody and/or syphilis (VDRL).
13. 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.
14. 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.
15. Abnormal baseline findings considered by the investigator to indicate conditions that might affect study endpoints.
16. 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.
17. 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.
18. Uncontrolled hypertension (systolic blood pressure [BP] >160 or diastolic BP >100mm Hg) or uncontrolled cardiac arrhythmias (Patients with hypertension controlled by antihypertensive therapies are eligible).
19. 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).
20. Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
21. 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.
22. 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 and pomelo-containing food or fluids.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Other
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To access the bioequivalence of the test product Doxorubicin Hydrochloride (Pegylated liposomal) concentrate for solution for infusion 20 mg/10mL (2 mg/ml) of Dr. Reddy’s Laboratories Ltd, Indiawith 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 and/or metastatic breast cancer patients
A total of 25 blood samples will be collected during each period. The predose sample of 5mL (0.00 hr) will be collected within 5 min. prior to dosing and blood samples of 5 mL each will be drawn at 0.33, 0.66, 1.00 (i.e. at end
of infusion), 1.25, 1.50, 2.00, 3.00, 4.00, 5.00, 6.00, 7.00, 8.00, 9.00, 10.00,
12.00, 16.00, 24.00(Day 2), 48.00(Day 3), 72.00(Day 4), 120.00(Day 6),168.00(Day 8),216.00(Day 10),288.00(Day 13) and 360.00(Day 16)hrs after start time of intravenous Infusion.
Secondary Outcome
Outcome
TimePoints
• To monitor the safety of the patients, who are exposed to the Investigational Medicinal Product
Physical examination,vital signs,ECG,laboratory evaluations and adverse event monitoring
Target Sample Size
Total Sample Size="70" Sample Size from India="70" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="124"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - YES
What data in particular will be shared? Response - All of the individual participant data collected during the trial, after de-identification.
What additional supporting information will be shared? Response (Others) -
Who will be able to view these files? Response - Anyone
For what types of analyses will this data be available? Response - Any purpose.
By what mechanism will data be made available? Response (Others) -
For how long will this data be available start date provided 01-01-2019 and end date provided 01-12-2021? Response (Others) -
Any URL or additional information regarding plan/policy for sharing IPD? Additional Information - NIL
Brief Summary
This study is Bioequivalence study
of Doxorubicin Hydrochloride (Pegylated liposomal) concentrate for solution for
infusion 20 mg/10mL (2mg/ml) of Dr. Reddy’s Laboratories Ltd, India, with that
of Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal)
concentrate for solution for infusion (20mg/10mL)] of Janssen-Cilag
International NV Turnhoutseweg 30 B-2340 Beerse Belgium in advanced ovarian
cancer and/or metastatic breast cancer patients under fed condition.
Treatments
will be allocated to subject by carrying out randomization using statistical
techniques. Blood samples will be collected prior to and after start of intravenous infusion on Day 1
(Period I), Day 29 (Period II).