CTRI/2018/07/014835 [Registered on: 12/07/2018] Trial Registered Prospectively
Last Modified On:
19/06/2019
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A Study of Doxorubicin Hydrochloride Liposome Injection in Subjects with Ovarian Cancer.
Scientific Title of Study
A Randomized, Open Label, Two Arm, Single Dose, Crossover, Bioequivalence Study of Ayana Pharma’s Doxorubicin Hydrochloride Liposome Injection (LC-101) (Investigational Product) and the US Reference Standard Doxorubicin
Hydrochloride Liposome Injection (SUN Pharma), in Subjects with Ovarian Cancer.
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Prashant Modi
Designation
General Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Department of Project Management & Regulatory Affairs, Lambda House, Plot No. 38, Survey No. 388 Near Silver Oak Club,
S. G. Highway, Gota Ahmadabad GUJARAT 382481 India
Phone
07940202375
Fax
07940202021
Email
prashantmodi@lambda-cro.com
Details of Contact Person Scientific Query
Name
Dr Ravi Alamchandani
Designation
Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Department of CTM Medical Services, Lambda House, Plot no. 38, Survey No. 388 Near Silver Oak Club,
S. G. Highway, Gota Ahmadabad GUJARAT 382481 India
Phone
07940202358
Fax
07940202021
Email
ravialamchandani@lambda-cro.com
Details of Contact Person Public Query
Name
Mr Prashant Modi
Designation
General Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Department of Project Management & Regulatory Affairs, Lambda House, Plot no. 38, Survey No. 388, Near Silver Oak Club,
S. G. Highway, Gota Ahmadabad GUJARAT 382481 India
Phone
07940202375
Fax
07940202021
Email
prashantmodi@lambda-cro.com
Source of Monetary or Material Support
Ayana Pharma Ltd, Hadassah Ein Kerem Campus
Minrav Building, Biotechnology Park POB 12133
Jerusalem 91120, Israel
Primary Sponsor
Name
Ayana Pharma Ltd
Address
Hadassah Ein Kerem Campus Minrav Building, Biotechnology Park POB 12133 Jerusalem 91120, Israel
No.1, Department of Clinical Research, Ramachandra Nagar, Porur- 600116 Chennai TAMIL NADU
9841092071
jovimartin4@gmail.com
Dr Rajeev L K
Sri Venkateshwara Hospital
#86, Department of Clinical Research, Room no. NA, Hosur Main Road-560068 Bangalore KARNATAKA
9880585797
lkrajeev@gmail.com
Dr Ankit Patel
Unique Hospital - Multispeciality and Research Institute
Opp. Kiran Motor, Department of Clinical Research, Room no. NA, Nr. Canal, Civil Hospital Char Rasta- Sosyo Circle Lane, Off. Ring Road-395002 Surat GUJARAT
7574808810
ankit_ahm1985@yahoo.com
Dr K B Akila
VGM Hospital
Institute of Gastroenterology
VGM Health Care Pvt Ltd,
No. 2100, Department of Clinical Research, 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 Liposome Injection
(LC-101) of Ayana Pharma Ltd
Dose: 2 mg/mL (50 mg/meter square dose); Frequency:
Single Dose; Mode of
Administration: Intravenous;
Duration of treatment: 60 minutes
Comparator Agent
Doxorubicin Hydrochloride Liposome Injection of Sun Pharma Global
Dose: 2 mg/mL (50 mg/meter square dose); Frequency: Single Dose; Mode of Administration: Intravenous; Duration of treatment: 60 minutes
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Female
Details
1. Adult female subjects between 18 to 65 years of age (both inclusive) at the time of screening visit.
2. Subjects with histologically or cytological proven ovarian cancer, whose disease has
progressed or recurred after platinum-based chemotherapy and scheduled to start therapy with or who are already receiving an approved dose of 50 mg per meter square Doxorubicin Hydrochloride Liposome Injection product.
3. Subjects expected to be able to receive both doses of Doxorubicin Hydrochloride Liposome
Injection.
4. Subjects eligible for receiving a dose of 50 mg per meter square of Doxorubicin Hydrochloride Liposome Injection.
5. Subjects with Performance less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) performance scale
6. Cardiac function (LVEF) greater than or equal to 50 percentage.
7. Adequate renal, hepatic and bone marrow function without blood product or hematopoietic
growth factor support.
8. Subjects able to understand the investigational nature of this study.
9. Availability of subject for the entire study period and willingness to adhere to protocol
requirements.
10. For subjects of child-bearing potential, serum beta HCG pregnancy test at screening and urine pregnancy test prior to dosing must be negative and subjects agree to use an acceptable and effective approved method of contraception
11. Subjects of non-childbearing potential who are either surgically sterile (hysterectomy,
bilateral oophorectomy, or bilateral tubal ligation) or greater than 1 year postmenopausal with follicle stimulating hormone in the postmenopausal range
12. Signed written informed consent.
ExclusionCriteria
Details
1. Subjects with history or presence of significant:
o Allergy or significant history of hypersensitivity or idiosyncratic reactions to a conventional formulation of Doxorubicin Hydrochloride and/or any components of
Doxorubicin Hydrochloride liposome injection.
o Clinically significant pulmonary, hepatic, renal, bone marrow, gastrointestinal,
endocrine, immunologic, dermatologic, musculoskeletal, neurological or psychiatric
disease.
o Impaired cardiac function
2. Alcohol dependence, alcohol abuse or drug abuse or addiction with any recreational drug
within the past one year.
3. Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, p. carinii or other microorganism (bacterial, viral or fungal).
4. Clinically significant illness (except ovarian cancer) within four weeks prior to dosing.
5. Prior radiation therapy to mediastinum
6. Concomitant use of other cytotoxic or cytostatic drugs or of radiotherapy within four
weeks prior to dosing
7. Subject under treatment of myelotoxic drugs, other than doxorubicin (liposomal).
8. Use of prescription or non-prescription herbal and dietary supplements, within 7 days prior to dosing.
9. Subjects with other known active malignancies requiring treatment within 3 years (except for ovarian and/or skin cancer).
10. Subjects with known brain metastasis and/or subjects considered for radiotherapy treatment.
11. Positive result to any of the following: HIV-1/2, hepatitis A, B and C; syphilis.
12. Use of CYP3A4 enzyme-modifying drugs in the previous 30 days prior to dosing and during the study
13. Subjects who have:
o Systolic blood pressure less than 90 mmHg or more than 160 mmHg
o Diastolic blood pressure less than 60 mmHg or more than 95 mmHg
o Pulse rate below 55 per min. or above 100 per min
14. Subjects with abnormal laboratory parameters
15. Subject is currently enrolled in, or has not yet completed a period of at least 30 days since ending other investigational device or drug trial(s).
16. Subjects who are legally detained in an official institute.
17. Subjects with prior doxorubicin exposure that would result in a total lifetime exposure of 550 mg per meter square or more after four cycles of treatment.
18. Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (e.g., compromise the well-being) of the subject or that could prevent, limit, or confound the protocol-specified assessments
19. Females of childbearing potential unwilling to use acceptable contraception (as identified in the protocol) throughout the trial and for 6 months after the last dose of study drug.
20. Pregnant or breast-feeding subjects.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Assessment of the bioequivalence and the safety of LC-101 (TEST Product) in comparison to the US Reference standard (REFERENCE product) in subjects with ovarian
cancer.
Throughout 14 days after both dosing.
Secondary Outcome
Outcome
TimePoints
NA
NA
Target Sample Size
Total Sample Size="42" Sample Size from India="42" Final Enrollment numbers achieved (Total)= "52" Final Enrollment numbers achieved (India)="52"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This study is a randomized, open label, two arm, single dose, crossover bioequivalence study. Study drug administration will be conducted on the days when the subjects are scheduled to receive their usual therapy so that treatment regimen is not altered. This study will be conducted in female subjects aged 18 to 65 years diagnosed 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 Hydrochloride Liposome Injection product. Doxorubicin hydrochloride liposome injection consists of doxorubicin hydrochloride, encapsulated in pegylated liposomes for intravenous administration. This study has an adaptive 2-stage design. A sufficient number of subjects with ovarian cancer shall be recruited to have approximately 42 evaluable subjects completing all follow up procedures. The expected duration of study participation for each subject is approximately 42 days from day of enrollment (day of dosing). An interim analysis of free and encapsulated doxorubicin will be performed at the end of Stage 1. If the bioequivalence of encapsulated and free doxorubicin has been established, then the study will be stopped. Otherwise, the study may continue into Stage 2 with additional number of ovarian cancer subjects. A final evaluation of bioequivalence based on free and encapsulated doxorubicin will be performed at the end of Stage 2 and will include all enrolled subjects completing the study.