CTRI/2017/07/009118 [Registered on: 27/07/2017] Trial Registered Prospectively
Last Modified On:
23/11/2018
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A comparative study of Doxorubicin Hydrochloride in ovarian and/or breast cancer patients.
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) of Dr. Reddy’s Laboratories Ltd, India, with that of Caelyx® [Doxorubicin Hydrochloride (Pegylated Liposomal)] of Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium in advanced ovarian cancer and/or metastatic breast cancer patients under fed condition
Trial Acronym
NA
Secondary IDs if Any
Secondary ID
Identifier
0076-17, Version 1.0 Dated 13 Feb 2017
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Ashutosh Chaudhary
Designation
Project Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda Therapeutic Research Ltd., Lambda House, Survey No.388, Near Silver Oak Club, S.G. Highway, Gota, Ahmedabad–382481, Gujarat. India
Ahmadabad GUJARAT 382481 India
Phone
07940202396
Fax
07940202021
Email
ashutoshchaudhary@lambda-cro.com
Details of Contact Person Scientific Query
Name
Dr Ravi Alamchandani
Designation
Assistant Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda Therapeutic Research Ltd., Lambda House, Survey No.388, Near Silver Oak Club, S.G. Highway, Gota, Ahmedabad–382481, Gujarat. India
Ahmadabad GUJARAT 382481 India
Phone
07940202358
Fax
07940202021
Email
ravialamchandani@lambda-cro.com
Details of Contact Person Public Query
Name
Dr Ravi Alamchandani
Designation
Assistant Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda Therapeutic Research Ltd., Lambda House, Survey No.388, Near Silver Oak Club, S.G. Highway, Gota, Ahmedabad–382481, Gujarat. India
Ahmadabad GUJARAT 382481 India
Phone
07940202358
Fax
07940202021
Email
ravialamchandani@lambda-cro.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
Dr Reddys Laboratories Ltd
Address
Integrated Product Development, Bachupally,
Quthubullapur Mandal,
Survey No: 42, 45 and 46,
R R Dist- 500 090,
Telangana., India.
Unique Hospital- Multispeciality & Research Institute
Dept of Clinical Research, Room No. NA, Opp. Kiran Motor Canal road, , Civil Hospital Char Rasta-Sosyo circle Lane, Off-ring road- 395002 Surat GUJARAT
9909918887
tanveermaksud@gmail.com
Dr K B Akila
VGM Hospital
Dept of oncology, Institute of Gastroenterology (VGM Health Care Pvt. Ltd.) No: 2100, Trichy road, Rajalakshmi mills Stop- 641005 Coimbatore TAMIL NADU
(1) ICD-10 Condition: C569||Malignant neoplasm of unspecifiedovary,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Doxorubicin Hydrochloride (Pegylated liposomal) concentrate for solution for
infusion 20 mg/10mL (2 mg/ml) by Dr. Reddy’s Laboratories Ltd, India
Dose: Single dose of 50 mg/m2 from 20 mg/10mL (2 mg/ml) vials;
Frequency: Once in every 28 days (1 Cycle); Mode of administration: IV infusion;
Duration: 28 days
Comparator Agent
Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated liposomal) concentrate for
solution for infusion (20
mg/10mL)] by Janssen-Cilag International NV, Belgium
Dose: Single dose of 50 mg/m2 from 20 mg/10mL vials; Frequency: Once in every 28 days (1 Cycle); Mode of administration: IV infusion; Duration: 28 days
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. Able to understand the investigational nature of this study and
give written informed consent prior to the participation in the
trial.
3. Subject with advanced ovarian cancer requiring Doxorubicin
and who have failed a first-line platinum-based chemotherapy
regimen (Disease progression / reoccurrence after platinum
based chemotherapy).
Or
As monotherapy for subjects with metastatic breast cancer
4. Cardiac function (left ventricular ejection fraction [LVEF]
≥50%.
5. Subject should have recovered from any toxic effects of
previous chemotherapy as judged by the Investigator.
6. Subject with life expectancy of at least 3 months.
7. Able to comply with study requirement in opinion of Principal
Investigator.
bin ≤ 1.5 × ULN
8. 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.
9. 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’s responsibility to ensure that above points regarding an effective method of avoiding pregnancy are discussed with subject in detail and subject agreed for this and it is documented in source document. The investigator should ensure that the subject is using an effective method of avoiding pregnancy as per protocol.
ExclusionCriteria
Details
1. Subjects who are pregnant or breast feeding.
2. Subjects with an ECOG (Eastern Cooperative Oncology group) Performance Status Score > 3.
3. Subject who had received prior treatment with any liposomal doxorubicin injection.
4. If total cumulative dose of Doxorubicin HCl approaches 450 mg/m2.
5. Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, P.carinii or other microorganism if under treatment with myelotoxic drugs.
6. Any other clinically significant liver or kidney disorders other than mentioned in the selection criteria.
7. 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. Subjects 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.
8. History of hypersensitivity reactions attributed to a conventional formulation of Doxorubicin Hydrochloride or the components
of Doxorubicin Hydrochloride Liposome (Pegylated Liposomal).
9. Use of any recreational drugs or history of drug addiction.
10. Known brain metastasis.
11. Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by NCI criteria.
12. Other serious illness or medical condition that would prohibit the understanding and giving of informed consent.
13. A positive hepatitis screen including hepatitis B surface antigen, HCV and HAV antibodies.
14. A positive test result for HIV antibody and/or syphilis (VDRL).
15. 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.
16. Any other condition that, in the investigator’s judgment, might
increase the risk to the subject or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
17. Abnormal baseline findings considered by the investigator to indicate conditions that might affect study endpoints.
18. 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 subject unlikely to fully complete the study, or any condition that presents undue risk from the study medication or procedures.
19. 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.
20. Uncontrolled hypertension (systolic blood pressure [BP] >160 or diastolic BP >100mm Hg) or uncontrolled cardiac arrhythmias (Subjects with hypertension controlled by antihypertensive therapies are eligible).
21. History of cerebrovascular accident (CVA), MI within 6 months or venous thrombosis within 12 weeks. (Subjects with previous history of venous thrombosis on a stable dose of anticoagulation are allowed).
22. Mental condition that would prevent subject comprehension of the nature of, and risk associated with, the study.
23. 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.
24. Subjects 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, grapefruit juice and pomelo-containing food or fluids.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To assess the bioequivalence of the Test Product relative to that of Reference Product in advanced ovarian
cancer and/or metastatic breast cancer patients under fed conditions
Day 1 and Day 29
Secondary Outcome
Outcome
TimePoints
To monitor the safety of the patients, who are exposed to the Investigational Medicinal Product
Day 1, Day 28 and Day 57.
Target Sample Size
Total Sample Size="70" Sample Size from India="70" Final Enrollment numbers achieved (Total)= "85" Final Enrollment numbers achieved (India)="85"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
Doxorubicin Hydrochloride Liposome (Pegylated liposomal) injection is a cytotoxic drug. This Bioequivalence study is proposed to be carried out in patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy or patients of metastatic breast cancer. Primary Objective of the study is to assess the bioequivalence of the test product relative to that of reference product. Secondary Objective of the study is to monitor the safety of the patients, who are exposed to the Investigational Medicinal Product. Two consecutive treatment cycles will be used for the two treatment periods and there will be a crossover between the two periods. Patients will be randomized to receive either test or reference product as per randomization schedule. There will be a washout period of at least 28 days between two successive dosing.