CTRI/2018/01/011550 [Registered on: 24/01/2018] Trial Registered Prospectively
Last Modified On:
21/11/2018
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 Liposome Injection 20 mg/10 mL (2 mg/mL) in patients with a cancer of female organs that produce eggs
Scientific Title of Study
A Multicentre, Open Label, Balanced, Randomized, Two-Treatment, Two-Period, Two-Sequence, Single Dose, Cross-Over, Bioequivalence Study of Doxorubicin Hydrochloride Liposome Injection 20 mg/10 mL (2 mg/mL) in comparison with Reference Doxorubicin Hydrochloride Liposome Injection 20 mg/10 mL (2 mg/mL) in Patients with Ovarian Cancer
Trial Acronym
NA
Secondary IDs if Any
Secondary ID
Identifier
0112-17, Version 1.0 Dated 14 Nov 17
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)
Name
Mr Harshvardhan Shrivastava
Designation
Project Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Plot no. 38, Survey No. 388 Near Silver Oak Club,
S. G. Highway, Gota Ahmadabad GUJARAT 382481 India
Phone
07940202396
Fax
07940202021
Email
harshvardhan@lambda-cro.com
Details of Contact Person Scientific Query
Name
Dr Ravi Alamchandani
Designation
Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Plot no. 38, Survey No. 388 Near Silver Oak Club,
S. G. Highway, Gota Ahmadabad GUJARAT 382481 India
(1) ICD-10 Condition: C569||Malignant neoplasm of unspecifiedovary,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Doxorubicin Hydrochloride Liposome Injection, 20 mg/ 10 mL (2 mg/mL) of Sun Pharmaceutical Ind. Ltd
Dose: 50 mg/meter square; Frequency: 4 weeks ; Mode of Administration: Intravenous Infusion ; Duration of treatment: Single Dose
Intervention
Doxorubicin Hydrochloride Liposome Injection, 20 mg/10 mL (2 mg/mL), of Intas
pharmaceuticals Ltd.
Dose: 50 mg/meter square; Frequency: 4 weeks
; Mode of
Administration: Intravenous Infusion ;
Duration of treatment: Single Dose
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Female
Details
1. Female patients between 18-75 years of age. (Both Inclusive)
2. Patients must be able to understand the investigational nature of this study and to
give written informed consent prior to the participation in the trial.
3. Patients with confirmed Ovarian Cancer requiring Doxorubicin
4. Patient with Ovarian Cancer whose disease has progressed or recurred after Platinum-based Chemotherapy and who are already receiving or scheduled to start the therapy with Doxorubicin Hydrochloride Liposome Injection, 20 mg/ 10
mL (2 mg/mL).
5. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
6. Cardiac function (left ventricular ejection fraction [LVEF] greater than or equal to 50 percentage.
7. Patient should have recovered from any toxic effects of previous chemotherapy as judged by the Investigator.
8. Patients with life expectancy of at least 3 months.
9. Able to comply with study requirement in the opinion of Investigator.
10. Adequate hematologic status, renal and liver function.
11. Females of reproductive potential must use an acceptable and effective method of avoiding
pregnancy, starting at least four weeks before the first dose of study drug and continuing until at least one month after the last dose of study drug.
12. 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.
ExclusionCriteria
Details
1. Pregnant or breast-feeding female.
2. Prior Doxorubicin exposure that would result in a total lifetime exposure of 550
mg/meter square 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. Significantly impaired hepatic function or kidney function
5. Impaired cardiac function
6. History of hypersensitivity reactions attributed to a conventional formulation of
Doxorubicin Hydrochloride or the components of Doxorubicin Hydrochloride
liposome injection.
7. Use of any recreational drugs (cocaine, amphetamines, barbiturates,
benzodiazepines, cannabinoids and morphine) or history of drug addiction.
8. Known brain metastasis.
9. Pre-existing motor or sensory neurotoxicity of a severity greater than or equal to 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 or HCV
antibodies.
12. Patients tested positive for HIV and/or syphilis.
13. The receipt of an investigational product, or participation in a drug research
study within a period of 30 days prior to the first dose of investigational Product
14. Any other condition/Abnormal baseline 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. Donation / loss of blood (without replenishment) (1 unit or 350 mL) within 90
days prior to receiving the first dose of study medicine.
16. Uncontrolled hypertension or uncontrolled cardiac arrhythmias (Patients with hypertension
controlled by antihypertensive therapies are eligible).
17. History of cerebrovascular accident (CVA), MI within 06 months or venous thrombosis within 12 weeks.
18. Patients who are smokers or tobacco users in any form.
19. Females of reproductive potential unwilling to use acceptable contraception (as defined in the protocol) throughout the trial and for one month after the last dose of study medication.
20. Past or current history of neoplasm other than the Ovarian Cancer and with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix.
21. Patients must not have taken any potent CYP3A4 inhibitors/inducers less than 30 days prior to enrolment 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 pomelocontaining food or fluids.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Assessment of bioequivalence of the sponsor’s test product [Doxorubicin Hydrochloride liposome
injection, 20 mg/10 mL (2 mg/mL) relative to that of reference product [Doxorubicin Hydrochloride
liposome injection, 20 mg/10 mL (2 mg/mL) in ovarian cancer patients.
Period-1
Day 1, 2, 3, 4, 6, 8 10, 12, 14 and 16
Period-2
Day 29, 30, 31, 32, 34, 36, 38, 40, 42 and 44
Secondary Outcome
Outcome
TimePoints
Safety of the patients, who are exposed to the Investigational Medicinal Products
Day 1 of period 1 to end of the study
Target Sample Size
Total Sample Size="66" Sample Size from India="66" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is a multicentre, open label, balanced, randomized, two-treatment, two-period, twosequence, single dose, cross-over, bioequivalence study. Doxorubicin liposomal injection is a cytotoxic drug. It would be unethical to do this study on healthy volunteers. Therefore, the Bioequivalence study is proposed to be carried out in patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy and who are already receiving or scheduled to start therapy with Doxorubicin liposomal injection therapy. Moreover, as per the guidance issued by office of Generic drugs, for Doxorubicin hydrochloride, also suggests Single-dose, two-way crossover in vivo study in the patients of Ovarian Cancer. In Period 1, patients will be dosed with Doxorubicin Hydrochloride liposome injection (either test or reference product as per the randomization schedule) on the first day of the chemotherapy cycle under standard diet condition. Patients will be crossed over to another arm in Period 2 after a wash out period of at least 28 days and will be dosed with Doxorubicin Hydrochloride liposome injection (either test or reference product as per the randomization schedule) on the first day of the chemotherapy cycle under standard diet condition. Total 66 patients will be enrolled in this study. The patients will have to stay for at least three consecutive nights in the facility. There will be a washout period of at least 28 days (window period of 14 days for adverse event management will be allowed between two periods of the study.) between two successive dosing. In case of any adverse event, necessary action will be taken till the event subsides. The study will commence only after a written approval is obtained from the Independent/Institutional Ethics Committee and applicable regulatory authorities.