CTRI/2022/12/048463 [Registered on: 26/12/2022] Trial Registered Prospectively
Last Modified On:
22/02/2024
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 20 mg/10 mL (2 mg/mL) in ovarian cancer subjects whose disease has progressed or recurred after platinum-based chemotherapy under standard diet (non-high-fat) conditions Subjects.
Scientific Title of Study
A randomized, open-label, balanced, multi-center, two-treatment, two-period, two-sequence, two-way crossover, single-dose, bioequivalence study of Doxorubicin Hydrochloride Liposome Injection 20 mg/10 mL (2 mg/mL) manufactured by Alembic Pharmaceuticals Limited, India with Doxorubicin Hydrochloride Liposome Injection 20 mg/10 mL (2 mg/mL) manufactured by Sun Pharmaceutical Ind. Ltd., India administered through intravenous infusion in ovarian cancer subjects whose disease has progressed or recurred after platinum-based chemotherapy under standard diet (non-high-fat) conditions.
Institutional Ethics Committee Government Medical College Aurangabad
Approved
Institutional Ethics Committee Government Medical College, Nagpur
Approved
Institutional Ethics Committee HCG Curie CCC
Approved
Institutional ethics committee Erode Cancer Centre
Approved
Institutional Ethics Committee For Human Research Medical College, Baroda
Approved
Institutional Ethics Committee HCG Cancer Centre
Approved
Institutional Ethics Committee Of OCH And RC
Approved
Institutional Ethics Committee, KLE University
Approved
KCC Institutional Ethics Committee
Approved
Manavata Clinical Research Institute Ethics Committee
Approved
Mumbai Oncocare Centre IEC
Approved
Narsimha Saraswati Medical Foundation
Approved
Nirmal hospital ethics committee
Approved
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 20 mg per 10 mL (2 mg per mL) Alembic Pharmaceuticals Limited
Dosage: 20 mg per 10 mL (2 mg per mL),
Route of Administration: Intravenous infusion,
Duration of Therapy: 28 Days, Frequency: Once in 28 days
Comparator Agent
Sun Pharmaceutical Ind, Ltd.
Doxorubicin Hydrochloride Liposome Injection 20 mg per 10 mL (2 mg per mL)
Dosage: 20 mg per 10 mL (2 mg per mL)
Route of Administration: Intravenous infusion
Duration of Therapy: 28 Days
Frequency: Once in 28 days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
Subjects will be considered eligible for the study based on the following criteria.
1. Willing and able to provide voluntary informed consent and to follow the protocol requirements.
2. Subject or caregiver able to communicate effectively with study personnel or investigator.
3. Female subjects between 18 and 75 years of age, both inclusive and having Body mass index (BMI) greater than or equal to 17.00 calculated as weight in kg per height in m2.
4. Histopathologically or cytologically confirmed ovarian cancer.
5. Documented progressive or recurrent disease after treatment with platinum based chemotherapy and who are already receiving or scheduled to start therapy on doxorubicin hydrochloride (liposomal).
6. Able and clinically indicated to receive the recommended minimum 2 cycles of liposomal doxorubicin HCl.
7. Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2.
8. Life expectancy of greater than 180 days at the time of enrollment.
9. Acceptable hematology status:
a. Hemoglobin greater than or equal to 9.0 g per dL
b. Absolute neutrophil count (ANC) greater than or equal to 1500 cells per micro L
c. Platelet count greater than or equal to 1, 00,000 cells per micro L
10. Acceptable liver function:
a. Alanine aminotransferase less than or equal to 2.0 X ULN
b. Aspartate aminotransferase less than or equal to 2.0 X ULN
c. Bilirubin less than 1.2 mg per dL
d. Alkaline phosphatase less than or equal to 2.0 X ULN (less than or equal to 5 × ULN for bone metastasis)
11. Subjects with Creatinine clearance greater than or equal to 60 mL per minute
12. Subject with left ventricular ejection fraction greater than or equal to 50 percent by an echocardiogram (ECHO) during screening.
13. Subjects with negative serum pregnancy test at screening and negative urine pregnancy test at Day 0.
14. 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 acceptable methods of contraception during the study and for 6 months after treatment discontinuation.
Acceptable methods of contraception are
a. Intrauterine device or intrauterine system
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
15. No history of addiction to any recreational drug or drug dependence or alcohol addiction
ExclusionCriteria
Details
Subjects will be excluded from the study based on the following criteria:
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 550 mg/m2 or more after four cycles of treatment. Failure or Intolerance to Doxorubicin hydrochloride that causes severe cardiotoxicity.
Note: Following conversion factor will be used to calculate total cumulative dose of doxorubicin.
Anthracycline agent Conversion factor
Doxorubicin 1
Epirubicin 0.5
Daunorubicin 0.5
Idarubicin 2.0
Mitoxantrone 2.2
3. Subject with impaired cardiac function including any of the following conditions within 6 months prior to screening:
a. Unstable angina
b. QTc prolongation (QTc of >470 msec (calculated by Bazett formula)) 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
4. Received any prior mediastinal irradiation (as cardiac toxicity may occur at cumulative doses lower than 400 mg/m2).
5. Receipt of any potential cardiotoxic drugs less than 2 weeks prior to dosing of Investigational Product.
6. Subjects taking or scheduled to receive strong inducers and inhibitors of CYP3A4, CYP2D6 or P-gp
7. Pregnant or lactating women.
8. History or presence of any uncontrolled systemic disease (e.g. cardiovascular disease, hypertension, diabetes mellitus etc.).
9. Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, Pneumocystis carinii, or other microorganism if under treatment with myelotoxic drugs.
10. Known central nervous system metastasis.
11. Major surgical procedure (including periodontal) within 28 days of first dose of Investigational Product.
12. Subjects with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV).
13. History of other malignancies in the last 5 years (except in situ cancer or basal or squamous cell skin cancer)
14. 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 greater 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).
15. 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.
16. Participation in any clinical study within 90 days before the first dose of Investigational Product.
17. Has consumed any alcohol or alcoholic products within 48 hours prior to IP administration on Day 1.
18. Has consumed any xanthine containing food or beverages (tea, coffee, chocolates or cola drinks), tobacco, tobacco containing products (like pan, pan masala, gutkha), beedi, cigarette within 24 hours prior to IP administration on Day 1.
19. Has consumed grapefruit or grapefruit products, pomelo-containing food or fluids and recreational drugs within 1 week prior to IP administration on Day 1.
20. Loss of greater than or equal to 350 ml of blood within 90 days before the first dose of Investigational Product.
21. Subject with confirmed novel coronavirus infection (COVID-19).
22. Subject who have taken vaccination for COVID-19 within 14 days before the day of first dosing.
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 20 mg/10 mL (2 mg/mL) manufactured by Alembic Pharmaceuticals Limited, India with Doxorubicin Hydrochloride Liposome Injection 20 mg/10 mL (2 mg/mL) manufactured by Sun Pharmaceutical Ind. Ltd., India administered through intravenous infusion in ovarian cancer subjects whose disease has progressed or recurred after platinum-based chemotherapy under standard diet (non-high-fat) conditions
A total of Twenty four (24) blood samples of 04.0 mL each will be collected for PK analysis in each period of the study. A total of 48 blood samples will be collected during the study.
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events and to ensure the safety of subjects
A total of twenty four (24) blood samples of 04.0 mL each will be collected for PK analysis in each period of the study. A total of 48 blood samples will be collected during the study.
Target Sample Size
Total Sample Size="68" Sample Size from India="68" Final Enrollment numbers achieved (Total)= "68" Final Enrollment numbers achieved (India)="68"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is randomized,
open-label, balanced, multi-center, two-treatment, two-period, two-sequence, two-way
crossover, single-dose, bioequivalence study of Doxorubicin Hydrochloride
Liposome Injection 20 mg/10 mL (2 mg/mL) manufactured by Alembic
Pharmaceuticals Limited, India with Doxorubicin Hydrochloride Liposome
Injection 20 mg/10 mL (2 mg/mL) manufactured by Sun Pharmaceutical Ind. Ltd.,
India administered through intravenous infusion in ovarian cancer subjects
whose disease has progressed or recurred after platinum-based chemotherapy
under standard diet (non-high-fat) conditions.