CTRI/2020/08/027025 [Registered on: 07/08/2020] 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
To compare the blood levels of liposomal Doxorubicin (Sun Pharma) with Caelyx® (Pegylated Liposomal doxorubicin)) in ovarian cancer or breast cancer patients
Scientific Title of Study
A multicenter, open label, randomized, balanced, two-treatment, three-period, three-sequence, single dose, replicate cross-over bioequivalence study of Doxorubicin Hydrochloride Pegylated Liposome Injection 2mg/mL (50 mg/m2 dose) of Sun Pharmaceutical Industries Ltd., India with that of Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal)] concentrate for solution for infusion of Janssen Pharmaceutica NV, Belgium in stable advanced ovarian cancer patients who have failed a first-line platinum based chemotherapy regimen or stable metastatic breast cancer patients under fed (standardized light meal) condition.
Trial Acronym
NA
Secondary IDs if Any
Secondary ID
Identifier
CBCC/2020/004, Version 1.0 dated 13/Apr/2020
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
Sun Pharmaceutical Industries Limited
Tandalja, Vadodara-390012, Gujarat, INDIA.
Vadodara GUJARAT 390012 India
Phone
9979879171
Fax
2652354897
Email
sanjay.paragi@sunpharma.com
Details of Contact Person Scientific Query
Name
Dr Sanjay Paragi
Designation
Senior Manager
Affiliation
Sun Pharmaceutical Industries Limited
Address
Sun Pharmaceutical Industries Limited
Tandalja, Vadodara-390012, Gujarat, INDIA.
Vadodara GUJARAT 390012 India
Phone
9979879171
Fax
2652354897
Email
sanjay.paragi@sunpharma.com
Details of Contact Person Public Query
Name
Dr Sanjay Paragi
Designation
Senior Manager
Affiliation
Sun Pharmaceutical Industries Limited
Address
Sun Pharmaceutical Industries Limited
Tandalja, Vadodara-390012, Gujarat, INDIA.
Behind Shivang Auto,
Mumbai Naka,
Nashik-422002, Maharashtra, India.
Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr M Pandidurai
Hindu Mission Hospital
No-103, GST Road,
West Tambaram, Chennai,
Tamil Nadu-600045, India.
Chennai TAMIL NADU
8248461542
pandi19@gmail.com
Dr Prakash SS
K R Hospital, Mysore Medical College and Research Institute
Department of General Surgery, K R Hospital, Mysore Medical College and Research Institute, Irwin Road, Mysore-570001, Karnataka, India. Mysore KARNATAKA
9901000589
prakashyesyes@yahoo.com
Dr Guru Prasad Mohanty
Kailash Cancer Hospital and Research Centre
Muni Seva Ashram, Goraj-391760,
Waghodia, Vadodara, Gujarat, India
Vadodara GUJARAT
9427432383
guru.prasad@greenashram.org
Dr D Raghunandan Rao MR
KIMS ICON Hospital
Room No. 35, 3rd Floor, Oncology Department, D. No. 32-11-02, Sheela Nagar, BHPV Post, Visakhapatnam -530012, Andhra Pradesh, India Visakhapatnam ANDHRA PRADESH
9246571537
rdigumarti@gmail.com
Dr Murli Subramanian
Medstar Specialty Hospital
614,17/1/3, Kodigehali Main Road, Sahakarnagar Post, Banglore-560092, Karnataka, India Bangalore KARNATAKA
9945813327
medstarclinicalresearch@gmail.com
Dr Sandhya Rani Nippani
MNJ Institute of Oncology and Regional Cancer Centre
Department of Radiotherapy,
Red Hills, Hyderabad-500004, Telangana, India
Hyderabad TELANGANA
9849352598
sandhyanippani@gmail.com
Dr Jayanti Patel
Nirmal Hospital Pvt Ltd.
Ring Road, Sagrampura,
Surat-395002, Gujarat, India.
Surat GUJARAT
8141397388
pateldrjayanti@gmail.com
Dr Anil Kumar MR
Onco Ville Cancer Hospital and Research Center
#4,80 feet road,&7th block, Nagarbhavi, Bengalore-560072,Karnataka, India Bangalore KARNATAKA
9739808502
dranil.onco@gmail.com
Dr Rakesh Neve
PDEA’ Ayurved Rugnalaya and Sterling Multispecialty Hospital
Room No. 109, Ground Floor, Sector 27, behind sweet junction, Pradhikaran, Nigdi, Pune - 411044, Maharashtra, India Pune MAHARASHTRA
9881143140
rakesh.neve@gmail.com
Dr Aniket Thoke
Sanjeevani CBCC USA Cancer Hospital
In front of Jain Mandir, Dawda colony, Pachpedi Naka, Raipur-492001, Chhattisgarh, India. Raipur CHHATTISGARH
(1) ICD-10 Condition: C796||Secondary malignant neoplasm of ovary, (2) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal)] concentrate for solution for infusion of Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, Belgium.
Dose: 50 mg/m2, Frequency: Once in 28 days, Duration: 3 Period, Mode of Administration: intravenous infusion
Intervention
Doxorubicin Hydrochloride Pegylated Liposome Injection 2mg/mL of Sun Pharmaceutical Industries Ltd., India.
Dose: 50 mg/m2,
Frequency: Once in 28 days,
Duration: 3 Period,
Mode of Administration: intravenous infusion
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 patients between 18 and 75 years of age, both inclusive and having Body mass index BMI greater or equal to 17.00 calculated as weight in kg per height in m2.
3. Histopathologically confirmed ovarian cancer or breast cancer
4. Patients with stable advanced ovarian cancer requiring Doxorubicin and who have failed a first-line platinum-based chemotherapy regimen. Or
5. Patients with stable metastatic breast cancer requiring Doxorubicin as monotherapy
6. Able and clinically indicated to receive the recommended minimum 3 cycles of liposomal doxorubicin HCl.
7. Eastern Cooperative Oncology Group ECOG performance status of less or equal to 2.
8. nLife expectancy of greater to 180 days based on clinical evaluation by the investigator at the time of screening.
9. Acceptable hematology status:
a. Hemoglobin greater or equal to 9.0 g per dL
b. Absolute neutrophil count ANC greater or equal to 1500 cells per µL
c. Platelet count greater or equal to 1,00,000 cells per µL
10. Acceptable liver function:
a. Alanine aminotransferase ALT less or equal to 2.5 x ULN
b. Aspartate aminotransferase AST less or equal to 2.5 x ULN
c. Total Bilirubin less than 1.2 mg per dL
d. Alkaline phosphatase less or equal to 3.0 x ULN less or equal to 5 × ULN for bone metastasis
11. Patients with Creatinine clearance greater or equal to 60 mL per minute
12. Left Ventricular ejection fraction greater or equal to 50 percent by echocardiogram ECHO during screening.
13. Patients 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 must agree to use effective method of contraception during dosing and up to six months after the last dose of study drug 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 patient
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
1. 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. Received previous chemotherapy 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. Received any prior mediastinal irradiation (as cardiac toxicity may occur at cumulative doses lower than 450mg/m2).
6. Receipt of trastuzumab within 24 weeks prior to dosing of Investigational Product and 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 greater or equal to 9 %) at screening.
10. Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, Pneumocystis carinii, or other microorganism if under treatment with myelotoxic drugs.
11. Known central nervous system metastasis
12. Major surgical procedure (including periodontal) within 28 days of first dose of Investigational Product.
13. Surgical or other non-healing wounds.
14. Patients with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV)
15. History of other malignancies in the last 5 years. (except in situ cancer or basal or squamous cell skin cancer)
16. 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 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. 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. Participation in any clinical study within 90 days before the first dose of Investigational Product.
19. Donation 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 who smokes or chew tobacco products.
21. Patients with pre-existing motor or sensory neurotoxicity of a severity greater or equal to grade 2 by NCI criteria.
22. Patients with history of other clinically significant concomitant disease including gastrointestinal, pulmonary, endocrine, immunologic, dermatologic, neurologic, psychological, musculoskeletal, cardiac, liver or renal disease.
23. Patient with uncontrolled hypertension (systolic blood pressure [BP] >180 or diastolic BP >100 mm Hg) with or without antihypertensive treatment.
24. Patient with history of cerebrovascular accident (CVA) within 6 months or venous thrombosis within 12 weeks. (Patients with previous history of venous thrombosis on a stable dose of anticoagulation are allowed).
25. Patient with a Coronavirus infection (COVID-19)
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 the test product (Doxorubicin Hydrochloride Pegylated Liposome Injection 2mg/mL) relative to that of reference product Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal)] concentrate for solution for infusion) in stable advanced ovarian cancer patients who have failed a first-line platinum based chemotherapy regimen or stable metastatic breast cancer patients.
A total of 18 PK blood samples will be collected in each period of the study. The pre-infusion blood sample (0.00) will be drawn within one hour prior to the scheduled infusion time and at 0.250, 0.500, 0.750, 1.000, 1.083, 1.250, 1.500, 2.000, 4.000, 6.000, 9.000, 25.000, 49.000, 97.000, 169.000, 241.000 and 337.000 hours after start of intravenous Infusion.
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events and to ensure the safety of patients.
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 on day 56, 57, 58 ,59, 61, 64, 67 and 71 in period 03 and during end of study.
Target Sample Size
Total Sample Size="54" Sample Size from India="54" Final Enrollment numbers achieved (Total)= "78" Final Enrollment numbers achieved (India)="78"
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, three-period, three-sequence, single dose, replicate cross-over bioequivalence study of Doxorubicin Hydrochloride Pegylated Liposome Injection 2mg/mL (50 mg/m2 dose) of Sun Pharmaceutical Industries Ltd., India with that of Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal)] concentrate for solution for infusion of Janssen Pharmaceutica NV in stable advanced ovarian cancer patients who have failed a first-line platinum based chemotherapy regimen or stable metastatic breast cancer patients under fed (standardized light meal) condition.
The primary Objective of study is to assess the bioequivalence of the test product (Doxorubicin Hydrochloride Pegylated Liposome Injection 2mg/mL) relative to that of reference product Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal)] concentrate for solution for infusion) in stable advanced ovarian cancer patients who have failed a first-line platinum based chemotherapy regimen or stable metastatic breast cancer patients.
90% confidence interval of the geometric mean ratio (GMR) of Cmax of the test and reference product for unencapsulated doxorubicin and encapsulated doxorubicin should be between 80.00% and 125.00% for ln-transformed data.
90% confidence interval of the geometric mean ratio (GMR) of AUC0-49 and AUC49-t of the test and reference product for encapsulated doxorubicin should be between 80.00% and 125.00%
for ln-transformed data.
“This study will be managed by CBCC Global research in agreement with
Sponsor (Sun Pharmaceutical Industries Limited)â€.