CTRI/2022/01/039082 [Registered on: 03/01/2022] Trial Registered Prospectively
Last Modified On:
14/03/2023
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
To compare the blood levels of liposomal Doxorubicin (Sun Pharma) with Doxil® (Pegylated
Liposomal doxorubicin)) in patients with platinum resistant recurrence or relapse mullerian carcinoma (epithelial ovarian cancer, primary fallopian tube cancer, peritoneal cancer)
Scientific Title of Study
A multicenter, open label, randomized, balanced, two-treatment, two-period, two-sequence, single dose, cross-over bioequivalence study of Doxorubicin hydrochloride liposome injection 2mg per mL (50 mg per m2 dose) of Sun Pharmaceutical Industries Ltd., India with that of DOXIL® (Doxorubicin hydrochloride liposome injection) 2mg per mL (50 mg per m2 dose) of Janssen Pharmaceutical, Tokyo, Japan in patients with platinum resistant recurrence or relapse mullerian carcinoma (epithelial ovarian cancer, primary fallopian tube cancer, peritoneal cancer) under fed (standardized light meal) condition
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CBCC/2020/034, Version 2.0, 29-Jul-2021
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sanjay Paragi
Designation
Senior Manager
Affiliation
Sun Pharmaceutical Industries Limited
Address
Clinical Pharmacology and Pharmacokinetics
Sun Pharmaceutical Industries Limited Tandalja, Vadodara
Gujarat, INDIA.
Vadodara GUJARAT 390012 India
Phone
91-9979879171
Fax
Email
sanjay.paragi@sunpharma.com
Details of Contact Person Scientific Query
Name
Dr Sanjay Paragi
Designation
Senior Manager
Affiliation
Sun Pharmaceutical Industries Limited
Address
Clinical Pharmacology and Pharmacokinetics
Sun Pharmaceutical Industries Limited Tandalja, Vadodara
Gujarat, INDIA.
Vadodara GUJARAT 390012 India
Phone
91-9979879171
Fax
Email
sanjay.paragi@sunpharma.com
Details of Contact Person Public Query
Name
Ms Simrit Reyar
Designation
Head - Quality Control (QC) and Monitoring (Senior General Manager)
Affiliation
Sun Pharmaceutical Industries Limited
Address
Sun House, Western express Highway, Goregaon (E) Mumbai
Mumbai MAHARASHTRA 400063 India
Phone
91-9810799354
Fax
Email
Simrit.reyar@sunpharma.com
Source of Monetary or Material Support
Sun Pharmaceutical Industries Limited, Plot No. 20, Second Floor, R&D-III, Sarhaul, Sector-18, Udyog Vihar
Industrial Area, Gurugram – 122015, Haryana, India
Primary Sponsor
Name
Sun Pharmaceutical Industries Limited
Address
Plot 20, Second Floor, R&D-III, Sarhaul, Sector 18, Udyog Vihar Industrial Area, Gurugram 122015, Haryana, India.
Opd-9,Aadhar Hospital Institute, Tosham Road,Near South bypass Crossing, Hisar,Haryana 125005, India Hisar HARYANA
9896539142
Drlovenish@gmail.com
Dr Kandappan Velavan
Erode Cancer Centre
Ground Floor, OPD 1, 1/393, Velevam Nagar, Near Chintamani Petrol Bunk Perundurai Road,
Thindal Medu, Thindal Erode- 638012, Tamilnadu, India. Erode TAMIL NADU
984233422
kvels@rediffmail.com
Dr PN Rajasekaran
Government Rajaji Hospital
Ground Floor, Government Rajaji Hospital, Alwarpuram, Madurai, Tamil Nadu, India 625020 Madurai TAMIL NADU
9380360432
pnnrrr@gmail.com
Dr K Pradeep Bhaskar
HCG Cancer Centre
HCG Cancer Centre, APIIC Health city,Plot No 10,Survey No 13P,,Chinnagadili,Arilova,Visakhapatanam-530040, AP,India Visakhapatnam ANDHRA PRADESH
8406907980
prabhaleo2003@gmail.com
Dr KL Priyadarshini
HCG city cancer centre
Conultation room 2, HCG city cancer centre, 33-25-33 CH Venkata, Gopala Krishnaiah St, Suryaraopeta, Vijayawada, Andhra Pradesh 520002, India Guntur ANDHRA PRADESH
9966030988
Priyadarshini006@gmail.com
Dr Rajnish Nagarkar
HCG Manavata cancer centre
Gorund floor OPD, HCG Manavata cancer centre behind shivang auto Mumbai Naka, Nashik-422002 Maharashtra,India Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr Niraj Bhatt
Kailash Cancer Hospital & Research centre
First Floor, Kailash Cancer Hospital & Research centre, Muniseva Ashram Goraj-391760, Waghodia, Vadodara, Gujarat, India Vadodara GUJARAT
9925581480
Niraj.bhatt@greenashram.org
Dr D Raghunadharao
KIMS- ICON Hospital
Room No. 32, 3rd floor, KIMS- ICON Hospital, #32-11-02, Sheela Nagar, BHPV Post, Vishakhapatnam-530012, Andhra Pradesh, India. Visakhapatnam ANDHRA PRADESH
9246571537
rdigumarti@gmail.com
Dr Prakash S S
KRH Mysore Medical College & Research Institute
Department of General surgery,KRH Mysore Medical College & Research Institute, Irwin Road, Mysore, Karnataka-570001, India Mysore KARNATAKA
9901000559
prakashyesyes@yahoo.com
Dr Balaji Shewalkar
Marathwada Regional Cancer Centre & Research Institute
Marathwada Regional Cancer Centre & Research Institute, Near Jama masjid, Aamkhas maidan road,Aurangabad, Maharashrta, 431001 Aurangabad MAHARASHTRA
9850632639
bshewalkar.pi@gmail.com
Dr Ananda Selvakumar
Meenakshi Mission Hospital & Research Centre
OPD 1, Meenakshi Mission Hospital & Research Centre ,Lake area, Melur Road, Madurai,Tamil Nadu-625107 Madurai TAMIL NADU
9894333759
drask81@yahoo.co.in
Dr Dhruv Mehta
Nirmal Hospital
Clinical research room, Nirmal Hospital PVT LTD, Ring road, Surat-365002, India Surat GUJARAT
9727053929
dr.dhruv.mehta14@gmail.com
Dr Anil Kumar
Oncoville Cancer Hospital & Research Centre
OPD 1,Oncoville Cancer Hospital & Research Centre ,No 4, 80ft Road, 7th Block Nagarbhavi 2nd stage,Bangaluru-560072, India Bangalore KARNATAKA
9739808502
dranil.onco@gmail.com
Dr Rakesh Neve
PDEAs Ayurved Rugnalaya and Sterling Multispeciality Hospital,
GF-109, PDEAs Ayurved Rugnalaya and Sterling Multispecality Hospital, Sector No. 27, Behind Sweet Junction, Pradhikaran, Nigdi,Pune -411044 Pune MAHARASHTRA
9881143140
rakesh.neve23@gmail.com
Dr Aniket Thoke
Sanjeevani CBCC USA Cancer Hospital
GF-101, Sanjeevani CBCC USA Cancer Hospital, in front of Jain Mandir , Dawada Colony, Pachpedi Naka, Raipur, Chattisgarh 492001 Raigarh CHHATTISGARH
9752929741
drthoke@gmail.com
Dr Vaibhav Chaudhary
Shalinitai Meghe Hospital and Research Center
Department of medicine, Shalinitai Meghe Hospital and Research Center,Wanadongri, Hingna Road, Nagpur-441110, Maharshtra,India Nagpur MAHARASHTRA
9833621049
dr.vaibhav155@gmail.com
Dr Yamini Patel
SSG Hospital
Oncology department OPD,SSG Hospital, Jail Rd, Indira Avenue, Vadodara, Gujarat-390000, India Vadodara GUJARAT
Institutional Ethics Committee Madurai Medical College and Govt Rajaji hospital
Approved
Institutional Ethics Committee, Meenakshi Mission Hospital & Research Centre,Madurai
Approved
Institutional Ethics Committee,SSG Hospital, Vadodara for Human Research Medical College
Approved
Institutional Ethics Committee- HCG Curie CCC
Approved
Institutional Ethics Committee- Oncoville Cancer Hospital & Research Centre
Approved
Institutional Ethics Committee HCG Cancer Centre
Approved
Manavata Clinical Research Institute Ethics Committee
Approved
Nirmal Hospital Ethics Committee, Surat
Approved
SMHRC Ethics Committee Shalinitai Meghe Hospital and Research
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
Comparator Agent
Reference Product
DOXIL® (Doxorubicin hydrochloride liposome injection) 2mg/mL (50 mg/m2 dose) of Janssen Pharmaceutical, Tokyo
Intervention
Test Product
Doxorubicin hydrochloride liposome injection 2mg/mL (50 mg/m2 dose) of Sun Pharmaceutical Industries Ltd., India
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Female
Details
1. Patient willing and able to provide voluntary informed consent prior to commencement of any study-related activities and the ability to follow the protocol requirements
2. Female patients between 18 and 75 years of age, both inclusive and having body mass index greater or equal to 17.00 calculated as weight in kg/height in m2.
3. Patients with histologically confirmed mullerian carcinoma (i.e., epithelial ovarian cancer, primary fallopian tube cancer, peritoneal cancer) which is platinum-resistant, recurrence or in relapse state.
4. Patient is able and clinically indicated to receive the recommended minimum of 2 cycles of liposomal doxorubicin HCl.
5. Patients having Eastern Cooperative Oncology Group performance status of lesser or equal to 2 at the time of screening
6. Life expectancy greater than 6 months based on the clinical evaluation by the investigator at the time of screening.
7. Patients with acceptable hematology status
a) Hemoglobin greater or equal to 9.0 g/dL
b) Absolute neutrophil count (ANC) greater or equal to 1500 cells/μL
c) Platelet count greater or equal to 75,000 cells/μL
d) White blood cell counts (/ mm 3): 3,000 or more and less than 10,000
8. Acceptable liver function:
a) Alanine aminotransferase (ALT) lesser or equal to 2.5 X ULN
b) Aspartate aminotransferase (AST) lesser or equal to 2.5 X ULN
c) Total Bilirubin less than 1.2 mg/dL
d) Alkaline phosphatase lesser or equal to 3.0 X ULN (lesser or equal to 5 × ULN for bone metastasis)
9. Patients with creatinine clearance greater or equal to 60 mL perminute
10. Patients with left ventricular ejection fraction greater or equal to 50 percent by an echocardiogram during screening.
11. Patients with a negative serum pregnancy test at screening and negative urine pregnancy test on Day 0 (only for females with child bearing potential)
12. Women of childbearing potential, (defined as women physiologically capable of becoming pregnant, unless, they must agree to use an effective method of contraception during dosing and up to six months after the last dose of study drug of the investigational product) practicing acceptable method of contraception.
Acceptable methods of contraception are:
a) Intrauterine device or intrauterine system
b) A 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 patient)
d) Female sterilization (surgical bilateral oophorectomy) or tubal ligation or
hysterectomy for at least 6 weeks or post-menopausal for at least one-year prior
to study participation
e) Total abstinence, partial abstinence is not acceptable.
13. Patients with no history of addiction to any recreational drug or drug dependence or alcohol addiction
ExclusionCriteria
Details
1. Patients with known hypersensitivity or contraindication including anaphylaxis to conventional or liposomal formulations of doxorubicin, anthracycline therapy, peanut or soya or to any of their components
2. Patients with prior doxorubicin exposure that would result in a total lifetime exposure of more than 450 mg/m2 (prior use of other anthracyclines or anthracenodiones should be included in calculations of total cumulative dosage)
3. Patients who have received previous chemotherapy and radiation therapy within 4 weeks of dosing of Investigational Product
4. Patients with impaired cardiac function including any of the following conditions within 6 months prior to screening:
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
5. Patients who have received any prior mediastinal irradiation as cardiac toxicity may occur at even lower doses (400mg/m2)
6. Patients who have received trastuzumab within 24 weeks prior to dosing of investigational product and who require as part of treatment during the study
7. Patients taking inducers and inhibitors of CYP3A4, CYP2D6 or P-gp
8. Pregnant or lactating women
9. Patients with uncontrolled metabolic disorders including diabetes mellitus (HbA1c ≥ 9 %) at screening
10. Patients with active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, Pneumocystis carinii, or other microorganism if under treatment with myelotoxic drugs
11. Patients with known central nervous system metastasis
12. Patients with major surgical procedure (including periodontal) within 28 days of the first dose of Investigational Product
13. Patients with surgical or other non-healing wounds
14. Patients with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV), syphilis.
15. Patients with history of other malignancies in the last 5 years (except in situ cancer or basal or squamous cell skin cancer)
16. Patients who have not recovered to Grade 0 or 1 toxicities from previous anticancer treatments or previous investigational agents. Exceptions are alopecia (any grade is acceptable), Hemoglobin greater or equal to 9.0 g/dL and fatigue (Grade 2 is acceptable) {Per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], V5.0}.
17. Patients with any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the patient to participate in the study including but not limited to cirrhosis or psychiatric illness/social situations that would limit adherence to study requirements.
18. Patients who have participated in any clinical study within 90 days before the first dose of Investigational Product
19. Patient who have donated blood and/or loss of greater or equal to 350 mL (1 unit) of blood within 90 days before the first dose of Investigational Product
20. Patients with pre-existing motor or sensory neurotoxicity of a severity greater or equal to grade 2 by NCI criteria.
21. Patients with a history of other clinically significant concomitant diseases including gastrointestinal, pulmonary, endocrine, immunologic, dermatologic, neurologic, psychological, musculoskeletal, cardiac, liver or renal disease, bleeding tendency.
22. Patient with uncontrolled hypertension (systolic blood pressure [BP] higher than 180 or diastolic BP higher than 100 mm Hg) with or without antihypertensive treatment
23. Patient with a history of cerebrovascular accident (CVA) within 6 months or venous thrombosis within 12 weeks (Patients with a previous history of venous thrombosis on a stable dose of anticoagulation are allowed)
24. Patients with confirmed novel coronavirus infection (COVID-19).
25. Patients who smokes or chew tobacco products
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
To assess the bioequivalence between Test product (Doxorubicin hydrochloride liposome injection 2mg/mL) and Reference product DOXIL® (Doxorubicin hydrochloride liposome injection 2mg/mL) in patients with platinum resistant recurrence or relapse mullerian carcinoma (epithelial ovarian cancer, primary fallopian tube cancer, peritoneal cancer) under fed (standardized light meal) condition
Pre dose(0.0 hrs_ within 1 hrs prior to dosing. 0.250, 0.500, 0.750 hrs after start of infusion, Immediately after end of infusion, 0.083, 0.250,0.500, 1.000,3.000,5.000,8.000, 24.000, 48.000, 96.000 , 168.000, 240.000 ,336.000 hrs after end of infusion
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events and to ensure the safety of patients after investigational product administration
Not applicable
Target Sample Size
Total Sample Size="64" Sample Size from India="64" 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)?
Response - NO
Brief Summary
A multicenter, open label, randomized, balanced, two-treatment, two-period, two-sequence, single dose, cross-over bioequivalence study of Doxorubicin hydrochloride liposome injection 2mg/mL (50 mg/m2 dose) of Sun Pharmaceutical Industries Ltd., India with that of DOXIL® (Doxorubicin hydrochloride liposome injection) 2mg/mL (50 mg/m2 dose) of Janssen Pharmaceutical, Tokyo, Japan in patients with platinum resistant recurrence or relapse mullerian carcinoma (epithelial ovarian cancer, primary fallopian tube cancer, peritoneal cancer) under fed (standardized light meal) condition.
Primary objective of the study is to assess the bioequivalence between Test product (Doxorubicin hydrochloride liposome injection 2mg/mL) and Reference product DOXIL® (Doxorubicin hydrochloride liposome injection 2mg/mL) in patients with platinum resistant recurrence or relapse mullerian carcinoma (epithelial ovarian cancer, primary fallopian tube cancer, peritoneal cancer) under fed (standardized light meal) condition