CTRI/2020/05/025245 [Registered on: 19/05/2020] Trial Registered Prospectively
Last Modified On:
12/05/2020
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Crossover Trial
Public Title of Study
Bioequivalence study of doxorubicin hydrochloride liposome injection 2mg/mL in ovarian cancer subjects under fasting conditions.
Scientific Title of Study
An open label, multi-center, randomized, two-treatment, two-period, two-sequence, two-way cross-over, single dose bioequivalence study of doxorubicin hydrochloride liposome injection 2mg/mL for intravenous infusion 50mg/m2 of shanghai jingfeng pharmaceuticals group co., ltd., china with DOXOrubicin hydrochloride liposome injection 2mg/mL for intravenous infusion 50mg/m2 of sun pharmaceuticals ind. ltd. in ovarian cancer subjects whose disease has progressed or recurred after platinum-based chemotherapy and who are already receiving or scheduled to start therapy on doxorubicin hydrochloride (liposomal) under fasting conditions.
Trial Acronym
CBCC/2019/019, Version 2.0 dated 09/Mar/2020.
Secondary IDs if Any
Secondary ID
Identifier
CBCC/2019/019, Version 2.0 dated 09/Mar/2020
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sandeep Singh
Designation
Director Operations
Affiliation
CBCC Global Research LLP
Address
Clinical Operations Department, Room Number 2, East Wing, Second Floor Skoda House, Opposite L. J Campus, S. G. Highway, Sarkhej, Ahmedabad – 382210, India.
Ahmadabad GUJARAT 382210 India
Phone
9637555304
Fax
9726434204
Email
sandeep.singh@cbccusa.com
Details of Contact Person Scientific Query
Name
Dr Sandeep Singh
Designation
Director Operations
Affiliation
CBCC Global Research LLP
Address
Clinical Operations Department, Room Number 2, East Wing, Second Floor Skoda House, Opposite L. J Campus, S. G. Highway, Sarkhej, Ahmedabad – 382210, India.
GUJARAT 382210 India
Phone
9637555304
Fax
9726434204
Email
sandeep.singh@cbccusa.com
Details of Contact Person Public Query
Name
Dr Sandeep Singh
Designation
Director Operations
Affiliation
CBCC Global Research LLP
Address
Clinical Operations Department, Room Number 2, East Wing, Second Floor Skoda House, Opposite L. J Campus, S. G. Highway, Sarkhej, Ahmedabad – 382210, India.
GUJARAT 382210 India
Phone
9637555304
Fax
9726434204
Email
sandeep.singh@cbccusa.com
Source of Monetary or Material Support
Shanghai Jingfeng Pharmaceuticals Group Co., Ltd., China
Primary Sponsor
Name
Shanghai Jingfeng Pharmaceuticals Group Co Ltd China
Address
50 Luoxin Rd., Baoshan District Shanghai 201908, China
3rd Floor, Clinical Research Department, Chinchwad Station Rd, Sudarshan Nagar, Pune, Maharashtra-411033, India. Pune MAHARASHTRA
8828017488
rnwategaonkar@gmail.com
Dr Prakash Kuppa
MNJ Institute of Oncology & Regional Cancer Center
3rd Floor, Red Hills, Hyderabad-500004, Telangana, India. Hyderabad TELANGANA
9849167371
drprakashmnj@gmail.com
Dr Chinmay Kumar Basu
Netaji Subhash Chandra Bose Cancer Hospital
2nd Floor, 3081, Nayabad Main Rd, New Garia, Pancha Sayar, Kolkata,-700094, West Bengal, India. Kolkata WEST BENGAL
9830114880
nscbcri2017@gmail.com
Dr Ghanashyam Biswas
Sparsh Hospital and Critical Care
Ground Floor, A/407, Back Side of Kalyan Jewellers, Saheed Nagar, Bhubaneswar -751007, Odisha, India. Bhadrak ORISSA
9937500878
drgbiswas@gmail.com
Details of Ethics Committee
No of Ethics Committees= 5
Name of Committee
Approval Status
Ethics Committee, N S C B C Research Institute
Submittted/Under Review
Lokmanya Medical Research Centre
Submittted/Under Review
Manavata Clinical Research Institute Ethics Committee
Approved
MNJ Institute of Oncology and Regional Cancer Centre
Submittted/Under Review
Sparsh Hospital and Critical Care
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C569||Malignant neoplasm of unspecifiedovary,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Doxorubicin hydrochloride liposome injection 2mg/mL for intravenous infusion 50mg/m2 of shanghai jingfeng pharmaceuticals group co., ltd., china.
The investigational product will be administered to each subject on Day 1 (Period 01) and Day 29 (Period 02) at a dose of 50mg/m2 as intravenous infusion via infusion pump over 60 minutes period (±5 minutes) as per the randomization schedule.
Comparator Agent
DOXOrubicin hydrochloride liposome injection 2mg/mL for intravenous infusion 50mg/m2 of sun pharmaceuticals India ltd.
The investigational product will be administered to each subject on Day 1 (Period 01) and Day 29 (Period 02) at a dose of 50mg/m2 as intravenous infusion via infusion pump over 60 minutes period (±5 minutes) as per the randomization schedule
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Female
Details
1. Willing and able to provide voluntary informed consent and to follow the protocol requirements
2. Female subjects between 18 and 75 years of age, both inclusive and having Body mass index BMI more than or equal to 17.00 calculated as weight in kg Per height in m2
3. Histopathologically confirmed ovarian cancer
4. Documented progressive or recurrent disease after treatment with platinum based chemotherapy
5. Able and clinically indicated to receive the recommended minimum 2 cycles of liposomal doxorubicin HCl
6. Eastern Cooperative Oncology Group ECOG performance status of less than or equal to 2
7. Life expectancy of more than 180 days at the time of enrollment
8. Acceptable hematology status
a. Hemoglobin more than or equal to 9 g Per dL
b. Absolute neutrophil count ANC more than or equal to 1500 cells Per Microlitre
c. Platelet count more than or equal to 1,00,000 cells Per Microlitre
9. Acceptable liver function
a. Alanine aminotransferase (ALT) less than or equal to 2X upper limit of normal ULN
b. Aspartate aminotransferase (AST) less than or equal to 2X ULN
c. Bilirubin less than 1.2 mg Per dL
d. Alkaline phosphatase less than or equal to 2.0 X ULN
10. Subjects with creatinine clearance more than or equal to 60 mL per minute.
11. Cardiac ejection fraction more than or equal to 50 percent by echocardiogram ECHO within 14 days prior to first dose of Investigational Product
12. Subjects with negative serum pregnancy test at screening and negative urine pregnancy test at Day 0
13. Women of child bearing potential, defined as women physiologically capable of becoming pregnant, unless they are using effective method of contraception during dosing of the investigational product practicing two acceptable methods of contraception
Acceptable methods of contraception are
A. Intrauterine device IUD or intrauterine system IUD or IUS
B. Double barrier method of contraception (Condom and occlusive cap or condom and spermicidal agent)
C. Male sterilization at least 6 months prior to the screening, should be the sole male partner for that subject
D. Female sterilization surgical bilateral oophorectomy) or tubal ligation at least 6 weeks prior to study participation
E. Total abstinence, partial abstinence is not acceptable
14. No history of addiction to any recreational drug or drug dependence or alcohol addiction
ExclusionCriteria
Details
1. Known hypersensitivity or contraindication including anaphylaxis to conventional or liposomal formulations of doxorubicin, anthracycline therapy or to any of their components.
2. Subjects with prior doxorubicin exposure that would result in a total lifetime exposure of 550mg/m2 or more after four cycles of treatment
3. Received previous chemotherapy less than 4 weeks prior to dosing of Investigational Product.
4. Recent (6 month) history of myocardial infarction or severe arrhythmias prior to dosing of Investigational Product.
5. Received any prior mediastinal irradiation (as cardiac toxicity may occur at cumulative doses lower than 400mg/m2).
6. Receipt of trastuzumab within 24 weeks prior to dosing of Investigational Product and during the study.
7. Receipt of cyclophosphamide, calcium channel blockers, and other potential cardiotoxic drugs for 2 weeks prior to dosing of Investigational Product, and during the study.
8. Subjects taking inducers and inhibitors of CYP3A4, CYP2D6 or P-gp
9. Pregnant or lactating women.
10. History or presence of any uncontrolled debilitating systemic disease (e.g. cardiovascular disease, hypertension, diabetes mellitus etc.)
11. Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, Pneumocystis carinii, or other microorganism if under treatment with myelotoxic drugs.
12. Known central nervous system metastasis.
13. Major surgical procedure (including periodontal) within 28 days of first dose of Investigational Product.
14. Surgical or other non-healing wounds.
15. Subjects with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV).
16. History of other malignancies in the last 5 years. (except in situ cancer or basal or squamous cell skin cancer)
17. Has not recovered to Grade 0 or 1 toxicity from previous anticancer treatments or previous investigational agents. Exceptions are alopecia (any grade is acceptable), Hemoglobin more than or equal to 9.0 g/dL, fatigue (Grade 2 is acceptable), and peripheral neuropathy (stable Grade 2 is acceptable) (Per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], V5.0).
18. Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the subject to participate in the study including but not limited to cirrhosis or psychiatric illness/social situations that would limit adherence to study requirements.
19. Participation in any clinical study within 90 days before the first dose of Investigational Product.
20. Donation and/or loss of more than or equal to 350 ml (1 unit) of blood within 90 days before the first dose of Investigational Product.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To assess the bioequivalence of doxorubicin hydrochloride liposome injection 2mg/mL of shanghai jingfeng pharmaceuticals group co., ltd., china with DOXOrubicin hydrochloride liposome injection 2mg/mL for intravenous infusion of sun pharmaceuticals ind. ltd. in ovarian cancer subjects whose disease has progressed or recurred after platinum-based chemotherapy and who are already receiving or scheduled to start therapy on doxorubicin hydrochloride (liposomal) under fasting conditions.
A total of 19 PK blood samples will be collected in each period of the study. The sample will be collected on day 0, 1, 2, 3, 5, 8, 11 and 15 in period 01 and on day 28, 29, 30, 31, 33, 36, 39 and 43 in period 02 and during end of study.
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events and to ensure the safety of subjects.
Safety assessment will be carried out during screening, on day 0, 1, 2, 3, 5, 8, 11 and 15 in period 01 and on day 28, 29, 30, 31, 33, 36, 39 and 43 in period 02 and during end of study.
Target Sample Size
Total Sample Size="22" Sample Size from India="22" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
N/A
Date of First Enrollment (India)
08/06/2020
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="0" Months="9" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
NIL
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
The study is An open label,
multi-center, randomized, two-treatment, two-period, two-sequence, two-way
cross-over, single dose bioequivalence study of doxorubicin hydrochloride
liposome injection 2mg/mL for intravenous infusion 50mg/m2 of shanghai jingfeng
pharmaceuticals group co., ltd., china with DOXOrubicin hydrochloride liposome
injection 2mg/mL for intravenous infusion 50mg/m2 of sun pharmaceuticals ind.
ltd. in ovarian cancer subjects whose disease has progressed or recurred after
platinum-based chemotherapy and who are already receiving or scheduled to start
therapy on doxorubicin hydrochloride (liposomal) under fasting conditions.
The primary Objective of study is to assess the
bioequivalence of doxorubicin hydrochloride liposome injection 2mg/mL of
shanghai jingfeng pharmaceuticals group co., ltd., china with DOXOrubicin
hydrochloride liposome injection 2mg/mL for intravenous infusion of sun
pharmaceuticals ind. ltd. in ovarian cancer subjects whose disease has
progressed or recurred after platinum-based chemotherapy and who are already
receiving or scheduled to start therapy on doxorubicin hydrochloride
(liposomal) under fasting conditions
The 90% confidence interval of the relative mean (Geometric mean) of the
test to reference formulation for Ln-transformed Cmax, AUC0-t and AUC0-inf
should be within 80.00% to 125.00% for Free doxorubicin and liposome
encapsulated doxorubicin to establish bioequivalence