CTRI/2015/02/005542 [Registered on: 13/02/2015] Trial Registered Prospectively
Last Modified On:
16/11/2016
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
Assess the safety & bioequivalence between (Test)Doxorubicin Hydrochloride Liposome Injection 2 mg/mL (50 mg/m2 dose) of SPIL and (Reference) Caelyx , Liposome Injection 2 mg/ml (50 mg/m2 dose) of Janssen-Cilag, in patients with metastatic breast cancer/advanced ovarian cancer, under fed conditions
Scientific Title of Study
A RANDOMIZED, OPEN LABEL, TWO TREATMENT, THREE PERIOD, THREE SEQUENCE, SINGLE DOSE, REPLICATED CROSSOVER, BIOEQUIVALENCE STUDY OF DOXORUBICIN HYDROCHLORIDE LIPOSOME INJECTION 2MG/ML (50MG/M2 DOSE) OF SUN PHARMACEUTICAL INDUSTRIES LIMITED AND CAELYX (DOXORUBICIN HYDROCHLORIDE) LIPOSOME INJECTION 2 MG/ML (50 MG/M2 DOSE) OF JANSSEN-CILAG INTERNATIONAL NV, IN PATIENTS WITH METASTATIC BREAST CANCER/ADVANCED OVARIAN CANCER, UNDER FED (STANDARDIZED NON HIGH-FAT MEAL) CONDITIONS
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
DOX_2I_4134_14, Version 00.,Dt:17/06/14;Amt02 Dt 26/11/14
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Aman Khanna
Designation
Associate Vice President
Affiliation
Medical Adviser,Sun Pharmaceutical Industries Ltd.
Address
Sun Pharmaceutical Industries Ltd.
Tandalja
Vadodara
Vadodara GUJARAT 390 020 India
Phone
91-265-2350789
Fax
91-265-2354897
Email
Aman.Khanna@sunpharma.com
Details of Contact Person Scientific Query
Name
Dr Aman Khanna
Designation
Associate Vice President
Affiliation
Medical Adviser, Sun Pharmaceutical Industries Ltd.
Address
Sun Pharmaceutical Industries Ltd.
Tandalja
Vadodara
Vadodara GUJARAT 390 020 India
Phone
91-265-2350789
Fax
91-265-2354897
Email
Aman.Khanna@sunpharma.com
Details of Contact Person Public Query
Name
Mr Durgesh Deshpande
Designation
Business Development
Affiliation
Project coordinator, Sun Pharmaceutical Industries Ltd.
Basavatarakam Indo American Cancer Hospital and Research Institute
Basavatarakam Indo American Cancer hospital and Research Institute, Block no.01, Room number 24 ground floor, Medical oncology department, Oncology division
Road No- 10,Banjarahills,
Hyderabad 500034,Telangana State, India.
Hyderabad ANDHRA PRADESH
4023551235
santa_a2002@yahoo.com
Dr Suresh Attili
BIBI General hospital & Cancer Centre
BIBI General hospital & Cancer Centre,Room No: 01 (ground floor)
Dept /Division : Oncology
16-3-991/1/C, Govt.Printing Press Road,
Malakpet, Hyderabad – 500024
Andhra Pradesh, India.
Hyderabad ANDHRA PRADESH
Erode Cancer Centre,
Room No: 01 (First floor)
Dept: Radiation Oncologist
Division: Oncology,
Velavan Nagar (Near Chinthamani Petrol Bunk),Perundurai Road, Thindal, Erode-638012 TamilNadu, India
Erode TAMIL NADU
04242339704
kvels@rediffmail.com
Dr Murali Subramanian
Gurushree Hi-Tech Multi-Specialty Hospital
Room No.2 (Basement)
Department of Oncology,
#1558 opp.chandra Layout Bus stand Vijaynagar Bangalore 560040
Bangalore
Bangalore KARNATAKA
Mahatma Gandhi Cancer Hospital & Research Institute
Mahatma Gandhi Cancer Hospital & Research Institute,Room No:1004 (ground floor)
Dept: Surgical Oncology
Division: Oncology,
1/7 MVP Colony, Visakhapatnam-530017, Andhra Pradesh, India. Visakhapatnam ANDHRA PRADESH
08912878787
muralivoona@yahoo.com
Dr Mahesh Srivastava
Mohan Hospital
Room Number 01, Ground Floor
Department of Oncology,
Mohan hospital,
Bhujpura Byepass Road,
Sasni Gate, Aligarah-202001, Aligarh UTTAR PRADESH
9897064628
maheshsrivastava72@reddiffmail.com
Dr Yathish Kumar HM
N.R.R Hospital
NRR Hospital,
Clinical and Surgical Oncology department,Oncology Division, Clinical Study Room, 3rd floor,
Room No 3&3A,
Hesaraghatta Main Road, Chikkasandra,
Near Chikkabanavara Railway Station, Bangalore-560090
Clinical Study Room, 3rd floor, Oncology Department
Bangalore KARNATAKA
9880462912
dryathish@hotmail.com
Dr Virendra Rajpurohit
Shri Ram Hospital
Clinical Research Room, Ground Floor,
Shri Ram Hospital.Oncology Division, Surgical Oncology department
Room N0.8, Pal Road,
Infront of Hanuvant School,
Jodhpur-342003.
Rajasthan
Jodhpur RAJASTHAN
Patients will be randomized to receive intravenous infusion (administered through infusion pump) of REFERENCE product of Doxorubicin Hydrochloride, Liposome injection 2 mg/ml (50 mg/m2 dose) by Intravenous Infusion after dilution, over 60-minute period, 2.5 hours after start of standardized non high-fat meal, on Day 1 (period I) , Day 29 (period II) and Day 57 (period III) according to randomization schedule generated using SAS® software.
Patients will be randomized to receive intravenous infusion (administered through infusion pump) of TEST product of Doxorubicin Hydrochloride, Liposome injection 2 mg/ml (50 mg/m2 dose) by Intravenous Infusion after dilution, over 60-minute period, 2.5 hours after start of standardized non high-fat meal, on Day 1 (period I) , Day 29 (period II) and Day 57 (period III) according to randomization schedule generated using SAS® software.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
i. Documented diagnosis of metastatic breast cancer (preferably on no other concomitant medication, however, if considered necessary, to be documented and given).
ii. Documented diagnosis of advanced ovarian cancer in patients who have failed a first-line platinum-based chemotherapy regimen (preferably on no other concomitant medication, however, if considered necessary, to be documented and given).
iii. Patients between 18 - 75 years of age (inclusive both).
iv. Patients with Performance ï‚£ 2 on the ECOG performance scale (listed in Appendix III).
v. Patients whose organ and Immune system function are adequate as indicated by the following laboratory values or considered by the Investigator/sub-Investigator to be of no clinical significance.
System Lab value
Hematologic
ANC ≥ 1.5 × 109 /L
Hb ≥ 9.0 g/dL
Platelets ≥ 100 × 109 /L
Renal
Sr. Creatinine ≤ 2.0 mg/dL
Hepatic
Total Bilirubin ≤ 1.5 mg/dL or ≤ 2 mg/dL (for liver mets)
AST & ALT ≤ 2.5 × ULN or ≤ 5 × ULN (for liver mets)
Alkaline phosphatase ≤ 5 × ULN (unless bone mets are p
esent in the absense of liver mets)
vi. Subject willing to give written consent according to section 15.3 of the protocol.
vii. Subjects must have clinically acceptable results for all the screening parameters.
viii. Availability of subject for the entire study period and willingness to adhere to protocol requirements as evidenced by written informed consent.
ix. Subjects
• of child bearing potential practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), such as sexual abstinence, birth control pills (if taken for at least 3 months prior to receiving the study medication), progestin injection or implants, condom plus spermicide, diaphragm plus spermicide, IUD, or vaginal spermicidal suppository. You agree to accept the risk that pregnancy could still result despite using birth control devices.
OR
• Postmenopausal for at least past 12 months.
OR
• Surgically sterile (bilateral tubal ligation / bilateral oophorectomy / hysterectomy has been performed on the subject).
ExclusionCriteria
Details
Subject who meets any of the exclusion criteria shall not be enrolled for this study:
i. Subject with a history of clinically significant gastrointestinal, dermatological, cardiovascular, renal, psychiatric, cerebrovascular, neurological, hepatic, pulmonary, or endocrine disease in the last 12 months.
ii. Allergy or Significant history of hypersensitivity reactions to a conventional formulation of doxorubicin HCl or the components of Doxorubicin Liposomal injection.
iii. Subjects who have no evidence of underlying disease which in the judgment of the investigator would not make the subject inappropriate for getting enrolled in the study (except metastatic breast cancer/advanced ovarian cancer) during screening medical history and whose physical examination are performed within 21 days prior to commencement of the study.
iv. Subjects determined by the study physician to have any medical condition that could jeopardize their health or prejudice the results.
v. Subjects with any clinically significant illness (except metastatic breast cancer/advanced ovarian cancer) within 4 weeks before the start of the study.
vi. Use of following drugs as concurrent therapy:
(Paclitaxel, Progesterone, Verapamil, Cyclosporine, Dexrazoxane, Cytarabine, Phenobarbital, Streptozocin).
vii. Subjects with a history of alcohol, drug or substance abuse in the past 12 months.
viii. Subjects who have used enzyme inducing or inhibiting drugs (like Phenytoin, Carbamazepine, Barbiturates, Griseofulvin etc.) within 30 days of Period 1 dosing.
ix. Subjects deemed uncooperative or noncompliant.
x. Subject who smokes or chew tobacco product.
xi. Difficulty in coming up for follow up
xii. Subject who is pregnant, lactating or likely to become pregnant or have a positive pregnancy test at screening or prior to check in of any of the three periods.
xiii. Abnormal 12 lead ECG, X-ray and 2D-Echocardiography finding.
xiv. Prior doxorubicin exposure that would result in a total lifetime exposure of >450 mg/m2 after four cycles of treatment.
xv. Subject having active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, herpes simplex, P. carinii, candidiasis, and mycobacterium avium complex and or other microorganism if under treatment with myelotoxic drugs.
xvi. Positive result to HIV, HCV, RPR and HBsAg.
xvii. Subjects who have participated in another clinical study for at least 90 days prior to first dosing
xviii. Blood donation within 90 days prior to first dosing.
xix. Subjects who have:
-Systolic blood pressure <90 mm of Hg or >140 mm of Hg
-Diastolic blood pressure <60 mm of Hg or >90 mm of Hg
-Minor deviations (2-4mm Hg) at check-in may be acceptable at the discretion of the investigator.
-Radial pulse rate <60/min. or >100/min.
Method of Generating Random Sequence
Permuted block randomization, fixed
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
• To assess the bioequivalence between Test product (A) and Reference product (B) in metastatic breast cancer/advanced ovarian cancer patients under fed (Standardized non high-fat meal) conditions by means of AUC0-t, Cmax and AUC0-∞
In each of the three study periods, 18 blood samples will be collected. A pre-dose blood sample of 10 mL will be collected within 1 hour prior to schedule dosing (before start of intravenous Infusion). Post-dose blood samples (4 mL each) will be collected 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 after start of intravenous Infusion.
Secondary Outcome
Outcome
TimePoints
To assess the safety of test product (A) and Reference Product (B) in metastatic breast cancer/advanced ovarian cancer patients
In each of the three study periods, 18 blood samples will be collected. A pre-dose blood sample of 10 mL will be collected within 1 hour prior to schedule dosing (before start of intravenous Infusion). Post-dose blood samples (4 mL each) will be collected 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 after start of intravenous Infusion.
Target Sample Size
Total Sample Size="54" Sample Size from India="54" Final Enrollment numbers achieved (Total)= "" Final Enrollment numbers achieved (India)=""
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This study is
Randomized, Open label, multi center, two treatment, three period, three
sequence, single dose, replicated crossover study, to assess
the safety of Test product (A) and Reference product (B) and to assess the bioequivalence between Test product Doxorubicin
Hydrochloride Liposome Injection 2 mg/mL (50 mg/m2 dose) of Sun
Pharmaceutical Industries Ltd. and Caelyx(Doxorubicin Hydrochloride) Liposome
Injection 2 mg/ml (50 mg/m2 dose)
of Janssen-Cilag International NV in metastatic breast cancer/advanced
ovarian cancer patients , under fed (Standardized non high-fat meal)
conditions.