CTRI/2017/03/008179 [Registered on: 22/03/2017] Trial Registered Prospectively
Last Modified On:
22/11/2018
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A study to evaluate the safety of Doxorubicin from Panacea Biotech Ltd (test drug) in comparison to the Doxorubicin of Sun Pharmaceuticals Ind. Ltd. (reference drug) in ovarion cancer patients
Scientific Title of Study
A randomized, multicenter, open label, two treatment, two period, two sequence, single dose, crossover, bioequivalence study of doxorubicin hydrochloride liposome injection for intravenous infusion 20 mg/10 ml (50mg/m2) of Panacea Biotec Ltd., India (investigational product) and doxorubicin hydrochloride liposome injection for intravenous infusion 20 mg/10 ml (50mg/m2) of Sun Pharmaceutical Industries ltd. (Reference drug), in patients with advanced ovarian cancer
Trial Acronym
NA
Secondary IDs if Any
Secondary ID
Identifier
1084-16, Version-1.1, Dated 22 Feb 2017
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Ravi A Panchal
Designation
Project Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda Therapeutic Research Ltd.,
Lambda House,
Survey No. 388, Near Silver Oak
Club, S.G. Highway, Gota,
Ahmedabad– 382481,
Gujarat.
India
Ahmadabad GUJARAT 382481 India
Phone
7940202546
Fax
07940202021
Email
raviapanchal@lambda-cro.com
Details of Contact Person Scientific Query
Name
Ravi Alamchandani
Designation
Assistant Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda Therapeutic Research Ltd.,
Lambda House,
Survey No. 388, Near Silver Oak
Club, S.G. Highway, Gota,
Ahmedabad– 382481,
Gujarat.
India
Ahmadabad GUJARAT 382481 India
Phone
7940202358
Fax
07940202021
Email
ravialamchandani@lambda-cro.com
Details of Contact Person Public Query
Name
Ravi Alamchandani
Designation
Assistant Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda Therapeutic Research Ltd.,
Lambda House,
Survey No. 388, Near Silver Oak
Club, S.G. Highway, Gota,
Ahmedabad– 382481,
Gujarat.
India
Ahmadabad GUJARAT 382481 India
Phone
7940202358
Fax
07940202021
Email
ravialamchandani@lambda-cro.com
Source of Monetary or Material Support
Panacea Biotech Ltd,B-1 Extn./G3, Mohan Co-Op. Industrial Estate,
Mathura Rd. New Delhi-110044, India.
Primary Sponsor
Name
Panacea Biotech Ltd
Address
B-1 Extn./G3, Mohan Co-Op. Industrial Estate,
Mathura Rd. New Delhi-
110044, India.
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NA
NA
Countries of Recruitment
India
Sites of Study
No of Sites = 15
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Jayanti Patel
Apple Hospital
Department of clinical Research, Room No: NA,Udhana Darwaja, Ring Road,
Surat-395002
Surat GUJARAT
02616696000
pateldrjayanti@gmail.com
Dr Jaiprakash Baraskar
Baraskar Hospital & Research center
276, Crystal Plaza, Department of clinical Research, Room No: NA, Central Bazar road, Ramdashpeth -440010 Nagpur MAHARASHTRA
9766789985
jpcancercare@gmail.com
Dr Gopichand M
City Cancer Centre
Room No. 1, Ground Floor, Department of clinical Research, City cancer centre, 33-25-33, Ch. Venkata krishnnaiyya street, Suryaraopet, Vijayawada - 520002 Krishna ANDHRA PRADESH
9885256059
mgopichand@yahoo.com
Dr Rajnish Vasant Nagarkar
Curie Manavta Cancer Centre
Curie Manavata Cancer Centre, Department of clinical Research, Room No: NA, Opp. Mahamarg Bus Stand, Mumbai Naka, Nashik - 422004, Maharashtra, India
Nashik MAHARASHTRA
9823061929
drraj@manavathacancercentre.com
DrArun Seshachalam
Dr.GVN Cancer Institute
No. 46, Department of clinical Research, Singarathope,
Trichy-620008, Tamil Nadu Tiruchirappalli TAMIL NADU
8754095758
arunonco@gmail.com
Dr Kakali Chaudhary
Health Point Multispecialty Hospital
Health Point Multispeciality Hospital, Department of clinical Research, Room No: NA, #21, Prannath Pandit Street, Opp. Lansdowne Padmapukur, Kolkata - 700025, West Bengal, India Kolkata WEST BENGAL
9883083052
mailkakalichoudhury@gmail.com
Dr Sharad Singh
J.K. cancer Institute
Rawatpur Crossing, Department of clinical Research, Room No: NA, Kanpur Kanpur Nagar UTTAR PRADESH
7052012777
meettosharad@gmail.com
Dr Kartikey Jain
Kailash cancer hospital & research center
Department of clinical Research, Room No: NA, Muni seva ashram, Goraj, Waghodia, Vadodara -391760 Vadodara GUJARAT
9427432642
kartikeya.jain@greenashram.org
Dr Minish Jain
KEM hosptial and Research Center
Day care Cancer Hospital, Department of clinical Research, Room No: NA, Banoo Coyaji Building, Rasta Peth, Sardar Moodliar Road, Pune Pune MAHARASHTRA
9665033134
drminishajain@yahoo.com
Dr Kirushna kumar
Meenakshi Mission Hospital & Research Centre
Meenakshi Mission Hospital & Research Centre, Department of clinical Research, Room No: NA, Lake Area, Melur Road, Madurai-625107, Tamilnadu, India.
Madurai TAMIL NADU
Sector 27, Near Bhel Chowk, Department of clinical Research, Room No: NA, Nigdi Pradhikaran, Pune, Maharashtra -411044 Pune MAHARASHTRA
9881143140
rakesh.neve@gmail.com
Dr Sandeep K Jasuja
R.K. Birla Caner center
department of medical oncology & BMT, Room No: NA, SMS Hospital, JNL Marg Jaipur RAJASTHAN
9783203814
sandeepjasuja@gmail.com
Dr Shailesh Bondarde
Shatabdi Hospital
Sujojit City center, Department of clinical Research, Room No: NA, Opp. Mahamarga Bus stand, Mumbai Mumbai MAHARASHTRA
9923346462
shaileshbondarde1971@gmail.com
Dr KC lakshmaiah
Srinivasan Cancer Care Hospital
236-1, Vijayashree Layout, Department of clinical Research, Room No: NA, Arekera, Bannerghatta Main Road, Banglore -560076 Bangalore KARNATAKA
9448055949
kcluck@gmail.com
Dr Tanveer Maksud
Unique Hospital- Multispeciality & Research Institute
Opp. Kiran Motor Canal road, Civil Hospital Char Rasta-Sosyo circle Lane, Department of clinical Research, Room No: NA, Off-ring road, Surat- 395002 Surat GUJARAT
0261-2636318
tanveermaksud@gmail.com
Details of Ethics Committee
No of Ethics Committees= 15
Name of Committee
Approval Status
Apple Hospital Ethics Committee, Dr Jayanti Patel
Submittted/Under Review
Baraskar Hospital Ethics Committee, Dr. Jaiprakash Baraskar
Submittted/Under Review
Ethics committee J. K cancer Institute, Dr. Sharad Singh
Submittted/Under Review
Ethics committee of SMS medical college and attached hospitals, Dr. Sandeep K Jasuja
Submittted/Under Review
Ethics committee, Unique Hospital-Multispeciality & research Institute, Dr. Tanveer Maksud
Approved
Health Point Ethics Committee, Dr Kakali Chaudhary
Submittted/Under Review
Institutional Ethics committee City Cancer Hospital, Dr. M. Gopichand
Submittted/Under Review
Institutional Ethics Committee Dr.GVN Cancer Institute, Dr.Arun Seshachalam
Submittted/Under Review
Institutional ethics committee MMHRC, Dr. Kirushna Kumar
Submittted/Under Review
Kailash cancer & medical center, Institutional Ethics committee, Dr. Kartikey Jain
Submittted/Under Review
KEM hosptial and Research Center,Ethics Committee, Dr. Minish Jain
Submittted/Under Review
Manavata Clinical Research institute ethics committee, Dr. Rajnish Vasant Nagarkar
Submittted/Under Review
Shatabdi Hospitals Ethic committee, Dr. Shailesh Bondarde
Submittted/Under Review
Srinivasan Cancer Care hospital, Institutional Ethics committee, Dr. K.C. lakshmaiah
Submittted/Under Review
Sterling hospital Institutional Ethics committee, Dr Rakesh Neve
(1) ICD-10 Condition: C569||Malignant neoplasm of unspecifiedovary,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Doxorubicin Hydrochloride Liposome Injection by Sun Pharmaceutical Ind.Ltd.India.
Dose:20 mg/10 mL (50 mg/m2) Duration: 28 days
Intervention
Doxorubicin Hydrochloride Liposome Injection.Panacea Biotec Ltd., India
Dose: 20 mg/10 mL (50 mg/m2) Duration: 28 Days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Female
Details
1. Female patients between 18-65 years of age. (Both Inclusive)
2. Patients must be able to understand the investigational nature of this study and to give
written informed consent prior to the participation in the trial.
3. Patients with histopathologically /cytologically confirmed Ovarian Cancer requiring
Doxorubicin
4. Patient with Ovarian Cancer whose disease has progressed or recurred after Platinum-based
Chemotherapyand who are already receiving or scheduled to start the therapy with
Doxorubicin.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
6. Cardiac function (left ventricular ejection fraction [LVEF] ≥50%.
7. Patient should have recovered from any toxic effects of previous chemotherapy as judged by
the Investigator.
8. Patients with life expectancy of at least 3 months.
9. Able to comply with study requirement in opinion of Investigator.
10. Adequate hematologic status, Renal and Liver function.
A]Hematologic status:
ANC ≥ 1500/mm3
Platelet count ≥ 100,000/mm3
Haemoglobin ≥ 9.0 g/dl
B]Renal function Serum Creatinine < 1.5 times ULN.
C]Hepatic Function:
AST and ALT < 2.5 times ULN
Alkaline phosphatase < 2 times ULN
phosphatase < 2 times ULN
Bilirubin < ULN
11. Sexually active women, unless surgically sterile (at least 6 months prior to Study drug
administration) or postmenopausal for at least 12 consecutive months, must use an effective
method of avoiding pregnancy (including oral, transdermal or implanted contraceptives [any
hormonal method in conjunction with a secondary method], intrauterine device, female
condom with spermicide, diaphragm with spermicide, absolute sexual abstinence, use of
condom with spermicide by sexual partner or sterile [at least 6 months prior to Study drug
administration] sexual partner) for at least 12 weeks prior to study drug administration,
during study and up to 30 days after the last dose of compassionate medications. Cessation
of birth control after this point should be discussed with a responsible physician.
The investigator should ensure that the patient is using an effective method of avoiding
pregnancy as per protocol.
12. Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of
minor surgery; at least 4 weeks must have elapsed from the time of major surgery.
ExclusionCriteria
Details
1. Pregnant or breast-feeding female.
2. Prior Doxorubicin exposure that would result in a total lifetime exposure of 550 mg/m2 or more after four cycles of treatment
3. Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, P.carinii or other microorganism if under treatment with myelotoxic drugs.
4. Significantly impaired hepatic function and kidney function.
5. Impaired cardiac function including any of the following conditions within past 6 months:
i. Unstable angina
ii. QTc prolongation or other significant ECG abnormalities.
iii. Coronary artery bypass graft surgery.
iv. Symptomatic peripheral vascular disease.
v. Myocardial infarction
vi. NYHA class II-IV heart failure
vii. Severe uncontrolled ventricular arrhythmias
viii. Clinically significant pericardial disease
ix. Electrocardiographic evidence of acute ischemic or active conduction system abnormalities
x. Patients with evidence of abnormal cardiac conduction (e.g., bundle branch block or heart block) are eligible if their disease has been stable for the past six months.
xi. Severe uncontrolled arrhythmias.
6. History of hypersensitivity reactions attributed to a conventional formulation of Doxorubicin Hydrochloride or the components of Doxorubicin Hydrochloride liposome injection.
7. Use of any recreational drugs (cocaine, amphetamines, barbiturates, benzodiazepines, cannabinoids and morphine) or history of drug addiction.
8. Known brain metastasis.
9. Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by NCI criteria.
10. Other serious illness or medical condition that would prohibit the understanding and giving of informed consent.
11. A positive hepatitis screen including hepatitis B surface antigen or HCV antibodies.
12. Known cases of HIV and/or syphilis.
13. The receipt of an investigational product, or participation in a drug research study within a period of 30 days prior to the first dose of investigational Product (Elimination half-life of the study drug should be taken into consideration for inclusion of the patient in the study).
14. Any other condition/Abnormal baseline that, in the investigator’s judgment, might increase the risk to the patient or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
15. Donation / loss of blood (without replenishment) (1 unit or 350 mL) within 90 days prior to receiving the first dose of study medicine.
16. Uncontrolled hypertension (systolic blood pressure [BP] >180 or diastolic BP >100mm Hg) or uncontrolled cardiac arrhythmias (Patients with hypertension controlled by antihypertensive therapies are eligible).
17. History of cerebrovascular accident (CVA), MI within 06 months or venous thrombosis within 12 weeks. (Patients with previous history of venous thrombosis on a stable dose of anticoagulation are allowed.)
18. Patients who are smokers or tobacco users in any form.
19. Past or current history of neoplasm other than the Ovarian Cancer and with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix.
20. Patients must not have taken any potent CYP3A4 inhibitors/inducers ≤ 30 days prior to enrolment including but not limited to: Ketoconazole, Itraconazole, Troleandomycin, Clarithromycin, Erythromycin, Ritonavir, Indinavir, Nelfinavir, Saquinavir, Amprenavir, Nefazodone, Fluvoxamine, Diltiazem, Verapamil, Mibefradil, Cimetidine, Cyclosporine, Grapefruit Juice and pomelo-containing food or fluids.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
Pharmacokinetivc Parameters namely, Cmax (Maximum Measured Plasma Concentration)
AUC0-t(Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration) and
AUC0- (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity)
Day 1 and Day 29.
Secondary Outcome
Outcome
TimePoints
To monitor the safety of the patients, who are exposed to the Investigational Medicinal Product
Day 1, Day 28 and Day 56.
Target Sample Size
Total Sample Size="32" Sample Size from India="32" Final Enrollment numbers achieved (Total)= "32" Final Enrollment numbers achieved (India)="32"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
Doxorubicin liposomal injection is a cytotoxic drug. It would be unethical to do this study on healthy volunteers. Therefore the Bioequivalence study is proposed to be carried out in patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy and who are already receiving or scheduled to start therapy with Doxorubicin liposomal injection therapy. Moreover, the guidance, issued by office of Generic drugs, for Doxorubicin hydrochloride suggests single-dose, two-way crossover in vivo study in the patients with ovarian cancer.