Bioequivalence study of Doxorubicin HCL Liposome Inj 20mg/10mL(Dose:50mg/m2) of Emcure Pharma
Ltd.,India, compared to that of Doxorubicin HCL Liposome Inj for IV Infusion
20mg/10mL(Dose:50mg/m2) OF
JANSSEN-CILAG INTERNATIONAL NV BELGIUM, in female patients with ovarian cancer in fasting condition
A MULTICENTER, OPEN LABEL, RANDOMIZED, BALANCED,
TWO-TREATMENT, TWO-PERIOD, TWO-SEQUENCE, SINGLE DOSE, TWO-WAY
CROSSOVER, BIOEQUIVALENCE STUDY OF DOXORUBICIN
HYDROCHLORIDE LIPOSOME CONCENTRATE FOR SOLUTION FOR
INFUSION 2 mg/mL AT A DOSE OF 50mg/m2 OF EMCURE PHARMACEUTICALS
LTD. INDIA, WITH CAELYX 2mg/mL CONCENTRATE FOR SOLUTION FOR
INFUSION (EACH mL CONTAINING 2 mg DOXORUBICIN HYDROCHLORIDE IN
A PEGYLATED LIPOSOMAL FORMULATION) AT A DOSE OF 50mg/m2 OF
JANSSEN-CILAG INTERNATIONAL NV BELGIUM, IN FEMALE PATIENTS WITH
ADVANCED OVARIAN CANCER WHO HAVE FAILED A FIRST-LINE
PLATINUM-BASED CHEMOTHERAPY REGIMEN AND WHO ARE ALREADY
RECEIVING OR SCHEDULED TO START THERAPY WITH THE DOXORUBICIN
HYDROCHLORIDE LIPOSOME INJECTION UNDER FASTING CONDITIONS.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
PCLPL-200-17 version no. 01 date 20 Feb 2018
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Simran Sethi MBBS
Designation
Head Clinical Trial
Affiliation
Panexcell Clinical Lab Private Limited
Address
Panexcell Clinical Lab Private Limited R-374 MIDC TTC Industrial area
Rabale Navi Mumbai
Mumbai
MAHARASHTRA India
Mumbai MAHARASHTRA 400701 India
Phone
Fax
Email
simran@panexcell.com
Details of Contact Person Scientific Query
Name
Dr Simran Sethi MBBS
Designation
Head Clinical Trial
Affiliation
Panexcell Clinical Lab Private Limited
Address
Panexcell Clinical Lab Private Limited R-374 MIDC TTC Industrial area
Rabale Navi Mumbai
Mumbai
MAHARASHTRA India
Mumbai MAHARASHTRA 400701 India
Phone
Fax
Email
simran@panexcell.com
Details of Contact Person Public Query
Name
Dr K Someswara Rao
Designation
General Manager
Affiliation
Emcure Pharmaceuticals Limited
Address
Emcure Pharmaceuticals Limited R&D Centre Uvarsad Square Sarkhej Gandhinagar
Highway Adalaj Dist Gandhinagar India
Gandhinagar
GUJARAT
India
Gandhinagar GUJARAT 382421 India
Phone
917930640153
Fax
Email
Someshwara.Rao@emcure.co.in
Source of Monetary or Material Support
Emcure Pharmaceuticals Ltd Plot No P2 ITBT Park MIDC Phase II Hinjwadi Pune 411057 India
Primary Sponsor
Name
Emcure Pharmaceuticals Ltd
Address
Plot No. P2, ITBT Park,
MIDC,Phase II, Hinjwadi,
Pune - 411057, India
Oncology Department,
Opp. Mahamarg Bus Stand,
Mumbai Naka, Nashik, Maharashtra – 422002, India Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr Kakali Choudhary
Health Point Hospital
Radiotherapy Department, 21, Prannath Pandit Street,
Opp: Lansdown Puddapukur, Kolkata - 7000025,
West Bengal, India. Kolkata WEST BENGAL
9883083052
drkakali23@gmail.com
Dr Raja G
Hindu Mission Hospital
Oncology department
103, GST Road, West Tambaram,
Tambaram, Chennai, Tamil Nadu 600045 Chennai TAMIL NADU
9841107677
rajaresearch17@gmail.com
Dr Bidisha Ghose Naskar
IPGME & R Oncology Department
Radiotherapy Department, 244 Acharya J.C. Bose Road, Kolkata - 700020,
West Bengal, India. Kolkata WEST BENGAL
9432164842
bghoshn@gmail.com
Dr Prakash SS
K.R. Hospital, MMC &RI
Department of General Surgery, Irwin Road, Next to Railway Station, Mysore- 570001, Karnataka, India. Mysore KARNATAKA
9901000559
prakashyesyes@yahoo.com
Dr Manasi Shah
Kailash Cancer Hospital & Research Centre
Department of Medical Oncology, Muni Seva Ashram, Goraj - 391760, Waghodia,Vadodara, Gujarat, India. Vadodara GUJARAT
9925581480
medonc12@gmail.com
Dr Mahesh Kumar Veeranna Kalloli
KLES Dr. Prabhakar Kore Hospital & Medical Research Centre
Deaprtment of Surgical onclolgy, KLES Dr. Prabhakar Kore Hospital & Medical Research Centre,
Nehrunagar, Belagavi – 590010, Karnataka, India Bangalore KARNATAKA
9945014996
mahesh.kalloli@gmail.com
Dr Suraj Pawar
Kolhapur Cancer Centre Pvt. Ltd.
R.S. 238, Opp. Mayur Petrol Pump, GokulShirgaon, Kolhapur-416234,
Maharashtra, India Kolhapur MAHARASHTRA
9822014908
surajpawar2001@yahoo.co.in
Dr Vibhore Mahendru
KRM Hospital And Research Centre
Oncology Department
Vijayant khand, Near Chinhat Crossing Gomti Nagar,
Lucknow 226010. Lucknow UTTAR PRADESH
9794811226
krmhrclko@gmail.com
Dr Srikanth Rao
MNJ Institute of Oncology & Regional Cancer Centre
Department of Radiation Oncology, Niloufer Road, Red Hills,
Bazar Ghat, Hyderabad,
Telangana –500004, India. Hyderabad TELANGANA
Deaprtment of oncology 86 Hosur Main Road Madiwala Bangalore Bangalore KARNATAKA
8971609070
knloki@gmail.com
DrKCLakshmaiah
Srinivasam Cancer Care Multi Speciality Hospital India Pvt. Ltd.,
Deaprtment of oncology, No.36, 1st A Main, 5th Cross, Nethravathi Street, Maruthi Nagar,
Nagarbhavi Main Road, Bangalore-560072 Bangalore KARNATAKA
09448055949
kcluck@gmail.com
Dr Neha Gupta
Sudbhawana Hospital
Department of Radiation oncology
B- 31/80, 23 B, Bhogabir, Lanka, Varanasi, Uttar Pradesh Varanasi UTTAR PRADESH
8004354185
drneha_500@yahoo.com
Dr Rajender Singh Arora
Sujan Surgical Cancer Hospital and Amravati Cancer Foundation
Department of medical oncology
52 B Shankar Nagar Main Road Amravati Amravati MAHARASHTRA
9823097573
rsaroradr@gmail.com
Dr Dr Tanveer Maksud
Unique Hospital
Department of Medical Oncology
Opp. Kiran Motor, Near Canal Civil Hospital-Char Rasta,
Sosyo Circle Lane Off, Ring Rd,
Surat, Gujarat 395002
Surat GUJARAT
ADVANCED OVARIAN CANCER WHO HAVE FAILED A FIRST-LINE
PLATINUM-BASED CHEMOTHERAPY REGIMEN AND WHO ARE ALREADY
RECEIVING OR SCHEDULED TO START DOXORUBICIN
HYDROCHLORIDE LIPOSOME INJECTION,
Manufactured by Emcure Pharmaceuticals Ltd., India.
Dosing: Patient will receive Doxorubicin Hydrochloride Liposome concentrate for solution for infusion 2 mg/mL at a dose of 50mg/m2 (either test or reference as per randomization in either period I or Period II). Total Two doses (Test and Reference) either in period I and II considering 28 days treatment cycle.
Comparator Agent
Doxorubicin Hydrochloride
Liposome Injection 20
mg/10 mL
Manufactured by:JANSSEN-CILAG INTERNATIONAL NV BELGIUM
Dosing: Patient will receive Doxorubicin Hydrochloride Liposome concentrate for solution for infusion 2 mg/mL at a dose of 50mg/m2 (either test or reference as per randomization in either period I or Period II).Total Two doses (Test and Reference) either in period I and II considering 28 days treatment cycle.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Female
Details
1. Female patients, 18 to 75 years of age (both inclusive) and having a Body Mass
Index (BMI) at least 17 kg/m2.
2. Have histologically or cytologically confirmed advanced ovarian cancer
3. Patients with advanced ovarian cancer who have failed a first-line platinum-based
chemotherapy regime and who are already receiving or scheduled to start
Doxorubicin Hydrochloride liposomal injection 50 mg/m2 dose as monotherapy as
per Investigator judgment.
4. Patients with life expectancy for at least 3 months.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (The
woman should be ambulatory, capable of all self-care, up for more than 50% of
waking hours. She may or may not be able to carry out any work activities).
6. Patients should preferably be on monotherapy. However, cancer patients receiving
concomitant medications are allowed to participate provided:
The concomitant medication and their dosing regimen are expected to be same for
both the study periods.
The concomitant medications do not interfere with the study drug (If concomitant
medication is required during the study period, the patients will be treated
accordingly, and a decision to continue or discontinue the patients will be made
by the investigator).
7. Availability of patient for the entire study period and willingness to adhere to
Protocol requirements as evidenced by the written ICF duly signed by the patient.
8. Either the female is of non-child bearing potential (females having documented
history of surgical sterilization or are postmenopausal (12 months of amenorrhea
after the last menstrual period) or if the female is of child bearing potential, then she
is eligible if:
Patient has used an effective method of contraception or abstinence from at least 4
weeks prior to study drug administration. Effective method includes:
Tubal sterilization (tubal ligation performed more than one month before Study
Day 1; transcervical tubal occlusion procedure performed more than six months
before Study Day 1)
Intrauterine Device (IUD)
Progestin Implant (i.e. Implanon or its equivalent)
Progestin injection or progestin oral contraceptive pill + one barrier method
(cervical cap, diaphragm, contraceptive sponge or vaginal spermicide + a male or
female condom)
Two barrier methods used together (cervical cap, diaphragm, contraceptive
sponge or vaginal spermicide + a male or female condom)
Absolute sexual abstinence (no sexual intercourse or genital contact with a male
partner)
Patient is willing to avoid pregnancies during the study and up to 06 months after
the last dose of study drug by use of an effective method of permitted
contraception or abstinence.
Patients having negative pregnancy test.
ExclusionCriteria
Details
Patients will be excluded from the study, if they meet any of the following criteria:
1. Patients who have a history of hypersensitivity or idiosyncratic reactions to a conventional or novel liposomal formulation of Doxorubicin HCl and its
excipients.
2. Prior Doxorubicin (or other anthracyclines) exposure that would result in a total
lifetime exposure of 550 mg/m2 or more after four cycles of treatment.
3. Patients who require any dose modifications (Dose other than 50 mg/m2)
4. Have received treatment with radiation therapy, chemotherapy, immunotherapy in
less than 4 weeks prior to study entry (6 weeks for nitrosoureas or Mitomycin C)
5. If any patient whose weight changes during the study requiring a ± 5% dose
adjustment will be discontinued from the study and excluded from the analysis.
6. If any signs or symptoms of extravasation have occurred, the infusion should be
immediately terminated and the patient will be discontinued from the study and
excluded from the analysis.
7. Known active brain metastasis including leptomeningeal involvement (patients
with brain metastases can only be enrolled if they are treated and stable for >8
weeks and who currently do not require steroid or radiation therapy)
8. Clinically significant Pre-existing toxicity by National Cancer Institute (NCI)
Common Terminology Criteria for Adverse Events (CTCAE) criteria. Mild to
moderate Pre-existing toxicity can be allowed only if in the opinion of
investigator, it will not require dose modification, will not interfere with the study
assessment and will not pose undue safety concerns to the patient. (“Palmar–
plantar erythrodysesthesia†and “Stomatitis†of grade 2 and above requires dose
modification, hence not allowed).
9. Patients with significantly impaired hepatic or renal function.
10. Significant history or current evidence of chronic - infectious,
cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological, metabolic
(endocrine), hematological, gastrointestinal, immunological or psychiatric
diseases, or organ dysfunction.
11. Laboratory parameters:
Patients with ANC < 1500/mm3
Platelet count < 100,000/mm3
Hemoglobin < 9.0 g/dl
Bilirubin >2.5 x ULN or if any dose modification required due to abnormal
bilirubin levels
Alkaline phosphatase, ALT, AST> 2.5 x ULN
For other laboratory parameters, the patient can be included if the values are
clinically non-significant in the opinion of investigator.
12. Patients with any of the following cardiac conditions:
Left ventricular ejection fraction (LVEF) <50 % as determined by ECHO
Clinically significant QTc prolongation, Uncontrolled arrhythmias, Acute
Ischemia, or other significant abnormalities as determined by ECG.
Prior history of Unstable angina in past 06 months.
Prior history of Myocardial infarction within the past 06 months.
New York State Heart Association (NYHA) class II-IV heart failure.
Any other cardiac illness that could lead to a safety risk to the patient in case
of enrolment in the study.
13. Pregnant or lactating woman.
14. 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.
15. Use of strong hepatic enzyme modifying drugs (like Phenytoin, Carbamazepine,
Barbiturates, Ketoconazole, Itraconazole, Clarithromycin, Erythromycin,
Ritonavir, Indinavir, Nelfinavir, Saquinavir, Nefazodone, Diltiazem, Verapamil,
Rifampicin and Cyclosporine) in the previous 30 days before the study.
16. Have major surgery, other than diagnostic surgery, within 4 weeks prior to study
entry.
17. Patients who have participated in another clinical trial within 90 days of study
start.
18. Donation of more than 350 ml of blood within 90 days prior to receiving the first
dose of IMP for the current study.
19. Have seizure disorders requiring anticonvulsant therapy.
20. Have known infection with human immunodeficiency virus (HIV I and II
antibodies), Hepatitis B or Hepatitis C.
21. Have an active, uncontrolled bacterial, viral, fungal, or other opportunistic
infections requiring systemic therapy.
22. Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma,
P. carinii or other microorganism if under treatment with myelotoxic drugs.
23. Poorly controlled hypertension or diabetes.
24. 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
patient or that could prevent, limit, or confound the protocol-specified
assessments.
25. History of alcohol dependence, alcohol abuse, drug abuse or addiction with any
recreational drug within the past one year.
26. Patients who have consumed caffeine and /or xanthine containing products (i.e.
coffee, tea, chocolate, and caffeine-containing sodas, colas, etc.), tobacco
containing products for at least 48.00 hours prior to check-in.
27. Patients who have consumed alcohol, grape fruit juice or its products 48 hours
before dosing.
28. Clinically significant cardiac, liver or kidney disease.
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
To assess the bioequivalence of Doxorubicin Hydrochloride Liposome
concentrate for solution for infusion 2 mg/mL at a dose of 50mg/m2 of Emcure
Pharmaceuticals Ltd., India, compared to that of Caelyx 2 mg/mL concentrate for
solution for infusion of Janssen-Cilag
International NV, Belgium., in female patients with advanced ovarian cancer
injection under fasting condition.
Pharmacokinetic sampling shall occur within 02 hours pre-dose, 0.00 and post dose
at 00.17, 00.33, 00.50, 00.67, 00.83,
01.00, 01.08, 01.25, 01.50, 01.75, 02.00, 03.00, 04.00, 06.00, 08.00, 12.00, 24.00, 48.00, 96.00, 144.00, 192.00,240.00, 288.00 and 336.00 hours.
To monitor the safety and tolerability of a single dose administered in female
patients with advanced ovarian cancer who have failed a first-line platinum-based
chemotherapy regimen and who are already receiving or scheduled to start therapy
with the doxorubicin hydrochloride liposome injection under fasting conditions
Measurement of seated blood pressure, pulse rate and wellbeing
enquiry will be performed prior to check-in, prior to start of infusion, after the
completion of infusion, at 02.00, 04.00, 08.00, 12.00 hours (±40 minutes) from the start of
infusion, at check-out and during ambulatory of both the periods and monitor AEs, SAEs.
Target Sample Size
Total Sample Size="56" Sample Size from India="56" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="67"
A Multicenter, Open label, Randomized, Balanced, Two-treatment, Two-period,Two-sequence, Single dose, Two-way crossover, Bioequivalence study in female
patients with advanced ovarian cancer who have failed a first-line platinum-based
chemotherapy regimen and who are already receiving or scheduled to start
therapy with the Doxorubicin Hydrochloride Liposome Injection under fasting
condition.
Primary Objective:
To assess the bioequivalence of Doxorubicin Hydrochloride Liposome
concentrate for solution for infusion 2 mg/mL at a dose of 50mg/m2 of Emcure
Pharmaceuticals Ltd., India, compared to that of Caelyx 2 mg/mL concentrate for
solution for infusion (each mL containing 2 mg doxorubicin hydrochloride in a
pegylated liposomal formulation) at a dose of 50mg/m2 of Janssen-Cilag
International NV, Belgium., in female patients with advanced ovarian cancer who
have failed a first-line platinum-based chemotherapy regimen and who are already
receiving or scheduled to start therapy with the doxorubicin hydrochloride liposome
injection under fasting condition.
Secondary objective:
To monitor the safety and tolerability of a single dose administered in female
patients with advanced ovarian cancer who have failed a first-line platinum-based
chemotherapy regimen and who are already receiving or scheduled to start therapy
with the doxorubicin hydrochloride liposome injection under fasting conditions.