CTRI/2012/08/002945 [Registered on: 31/08/2012] Trial Registered Retrospectively
Last Modified On:
13/03/2014
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A Clinical trial intended to compare two formulations of Capecitabine tablets, in patients with Breast Cancer, Duke’s C Colon Cancer or Colorectal Cancer.
Scientific Title of Study
An Open-label, Randomized, Three-period, Two-treatment, Three-sequence, Reference replicated, Crossover, Multicentre, Single-dose Bioequivalence Study of Capecitabine Tablets 500 mg of Cadila Healthcare Ltd., India and ‘XELODA®’ (Capecitabine) Tablets 500 mg of Genentech USA Inc., USA in Metastatic Breast Cancer, Duke’s C Colon Cancer or Metastatic Colorectal Cancer Patients under Fed Conditions
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
CRL/CT/08/11-12; Version 2.0 dated May 24, 2012
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Charu Gautam
Designation
Director- Global Clinical Operations
Affiliation
Clinatha Research Ltd.
Address
Cliantha Research Ltd.
Opposite Pushparaj Towers
Nr. Judges Bungalows
Bodakdev, Ahmedabad - 380 054
Gujarat, India
Ahmadabad GUJARAT 380 054 India
Phone
07966135655
Fax
07966135641
Email
cgautam@cliantha.in
Details of Contact Person Scientific Query
Name
Dr Charu Gautam
Designation
Director- Global Clinical Operations
Affiliation
Clinatha Research Ltd.
Address
Cliantha Research Ltd.
Opposite Pushparaj Towers
Nr. Judges Bungalows
Bodakdev, Ahmedabad - 380 054
Gujarat, India
GUJARAT 380 054 India
Phone
07966135655
Fax
07966135641
Email
cgautam@cliantha.in
Details of Contact Person Public Query
Name
Mr Chirag Shah
Designation
Head- Clinical Trials
Affiliation
Clinatha Research Ltd.
Address
Cliantha Research Ltd.
Opposite Pushparaj Towers
Nr. Judges Bungalows
Bodakdev, Ahmedabad - 380 054
Gujarat, India
Department of Oncology, Bibi General Hospital And Cancer Centre, 16-3-991/1/C, Government Printing Press Road, Malakpet,
Hyderabad - 500 024
Hyderabad ANDHRA PRADESH
04024528122
sureshattili@yahoo.com
Dr Ajay Mehta
Central India Cancer Research Institute
Department of Oncology, ist Floor, CENTRAL INDIA CANCER RESEARCH INSTITUTE, 11, SHANKAR NAGAR, WEST HIGH COURT ROAD, NAGPUR, MAHARASHTRA -440 010 Nagpur MAHARASHTRA
9823190192
ajayonco@hotmail.com
Dr M Gopichand
City Cancer Centre
City Cancer Centre, 33-25-33, Ch. Venkata Krishnayya street, Suryarao pet, Vijayawada , Andhra Pradesh – 520002 Hyderabad ANDHRA PRADESH
9885256059
mgopichand@yahoo.com
Dr Rajnish Nagarkar
Curie Manavta Cancer Centre
Curie Manavta Cancer Centre, Department of Radiation Oncology, Opp. Mahamarg Bus Stand,
Mumbai Naka, Nasik- 422004 Nashik MAHARASHTRA
9823061929
drrajnagarkar@yahoo.co.in
DR G N PATEL
Jeevandeep Oncosurgical Hospital
JEEVANDEEP ONCOSURGICAL HOSPITAL, 302, 3RD FLOOR, AYUSH BUILDING, NEAR PARAM DOCTOR HOUSE, LAL DARWAJA, STATION ROAD, SURAT, GUJARAT- 395003 Surat GUJARAT
9376913131
gnonco@gmail.com
Dr Manav Rakshak
Manav Rakshak Cancer Hospital
Manav Rakshak Cancer Hospital, 125, Pocket-2, Jasola, Near Apolo Hospital, New Delhi-110025 New Delhi DELHI
9810023205
manavrakshak@hotmail.com
Dr Minish Jain
Noble Hospital
Noble Hospital, 153, Magarpatta City Road, Pune, Maharashtra- 411 013 Pune MAHARASHTRA
9823133390
minishjain009@gmail.com
Dr Shailesh Bondarde
Shatabdi Superspeciality Hospital
Department of Oncology,Shatabdi Superspeciality Hospital, Suyojit City Centre, Mumbai Naka, Opposite Mahamarg Bus stand,
Nasik - 422 005 Nashik MAHARASHTRA
9822012427
shalakatamane@gmail.com
Dr Pradeep Shah
Shreyas Medical clinic and Hospital
Shreyas Medical clinic and Hospital, 2-premal appartment, Raopura, Vadodara 390001 Vadodara GUJARAT
Central Ethics Committee, Delhi- Dr. Manav Rakshak Cancer Hosp. Delhi
Approved
Central India Cancer Foundation Ethics Committee, Nagpur, Central India Cancer Institute- Dr. Ajay Mehta, Nagpur
Approved
Ethical Trial Of Health In Community Ethics Committee, Surat, Dr. G. N. Patel
Approved
Ethics Committee of Balaji Hospital, Baroda, Dr. Pradeep Shah, Baroda
Approved
Ethics Committee Shatabdi Super Speciality Hospital, Shatabdi Super Speciality Hospital- Nashik, Dr. S. Bondarde- Nashik
Approved
Institutional ethics committee Nobel Hospital, Pune- Dr. Minish Jain
Approved
Institutional Ethics Committee, Bibi General Hospital and Cancer Centre, Hyderabad, Dr. S. Attili, Hyderabad
Approved
Institutional Ethics Committee, City Cancer Centre, Vijayawada, Dr. M. Gopichand, Vijayawada
Approved
Manavata Clinical Research Institute-Professional Ethics Committee, Nashik, Curie Manavata Cancer Centre, Dr. R. Nagarkar, Nashik
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
Patients with Metastatic Breast Cancer, Duke’s C Colon Cancer or Metastatic Colorectal Cancer,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Capecitabine 500 mg tablets
Capecitabine 1250 mg/m2 administered twice daily orally; BD morning and evening; equivalent to 2500 mg/m2 total daily dose for 14 days including of three study periods.
Intervention
XELODA® -Capecitabine 500 mg tablets
Capecitabine 1250 mg/m2 administered twice daily orally :BD (morning and evening; equivalent to 2500 mg/m2 total daily dose) for 14 days including of three study periods.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
79.00 Year(s)
Gender
Both
Details
1) Patients must be receiving stable doses of Capecitabine (e.g.: 2500 mg/m2/day in two divided doses of 1250 mg/m2 , for 2 weeks followed by a 1 week rest period given as 3 week cycles) for the treatment of metastatic breast cancer, Duke’s C colon cancer following complete resection, and metastatic colorectal carcinoma. Patients must have completed at least one cycle.
2) Males or non pregnant or non lactating females of age ≥ 18 years and ≤ 79 years.
a) Females of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-HCG) pregnancy test performed within 28 days prior to initiation of the study & at the time of check-in of each period.
b) Acceptable forms of contraception include the following:
i. Intrauterine device in place for at least 3 months prior to the start of the study and remaining in place during the study period, or
ii. Barrier methods containing or used in conjunction with a spermicidal agent, or
iii. Surgical sterilization, or
iv. Practicing sexual abstinence throughout the course of the study
c) Females will not be considered of childbearing potential if one of the following is reported and documented on the medical history:
i. Postmenopausal with spontaneous amenorrhea for at least one year, or
ii. Bilateral oophorectomy with or without a hysterectomy and an absence of bleeding for at least 6 months, or
iii. Total hysterectomy and an absence of bleeding for at least 3 months
3) Life expectancy of at least 3 months.
4) Patients willing to not change their concurrent medications during the study.
5) All patients should have a Body Mass Index (BMI) less than or equal to 35 but greater than or equal to 18. BMI values should be rounded to the nearest integer. (e.g. 35.4 rounds down to 35, while 17.5 rounds up to 18)
6) Able to comply with Protocol requirements and assessments
7) Able to give written informed consent to participate in the study
8) All patients should be judged eligible by the principal investigator or co-investigator or physician during a pre-study safety assessment performed within 28 days of the first dose of study medication which will include
a) A complete medical history
b) A normal or clinically non-significant physical examination.
c) Within normal limits or clinically non-significant laboratory evaluation results (unless otherwise noted in the exclusion criteria) for the following tests
ExclusionCriteria
Details
Subject candidates must not be enrolled in the study if they meet any of the following criteria:
1. History of allergic responses to Capecitabine, or other related drugs and any of its formulation ingredients or 5-fluorouracil.
2. Patients receiving concomitant therapy of warfarin (coumarin anticoagulants) or history of usage of coumarin anticoagulants in the previous three months prior to study start (dosing).
3. Known history of dihydropyrimidine dehydrogenase deficiency
4. Consumption of grapefruit, grapefruit-like or grapefruit containing products within 7 days of drug administration.
5. Ingestion of any alcoholic, caffeine or xanthine containing food or beverage within the 48 hours prior to the initial dose of study medication.
6. Use of enzyme-modifying drugs within 30 days prior to receiving the first dose of study medication (listed in Appendix-II). They can be allowed depending on Principal Investigator’s discretion in consultation with Medical monitor, if they are kept constant in the last 30 days and are expected to remain constant during the study period.
7. History of moderate (30-50 ml/min creatinine clearance) or severe (≤ 30 ml/min creatinine clearance) renal disease.
8. Impaired hepatic function (bilirubin ≥2.5 times the upper limit of normal, transaminases or alkaline phosphatase ≥ 2.5 times the upper limit of normal).
9. Major surgery to the gastrointestinal tract, the liver or kidney within 4 weeks of study entry which may impact on the pharmacokinetics of Capecitabine.
10. Participation in any investigational drug study within 30 days prior to period 1 dosing.
11. History of difficulty in swallowing, or any gastrointestinal disease which could affect drug absorption.
12. History of peptic ulcer, ulcerative colitis, ulcerative stomatitis and/or lack of physical integrity of the upper intestinal tract.
13. Patients with History of coronary artery disease.
14. Patients with prolonged QT or clinically significant ECG changes
15. Known, existing uncontrolled coagulopathy.
16. Donation or loss of blood or plasma of one unit (about 450 mL whole blood or 220 mL plasma) in the previous 60 days.
17. Any significant disease or condition which might compromise the haemopoeitic, gastrointestinal, renal, hepatic, cardiovascular, respiratory, central nervous system, diabetes, psychosis or any other body system.
18. History of drug dependence, history of alcoholism in the past 2 years prior to screening.
19. Smokers, who smoke more than or equal to 10 cigarettes per day or more than or equal to
20 biddies per day or those who cannot refrain from smoking during study period.
20. History of difficulty with donating blood or difficulty in accessibility of veins or intolerance to venipuncture.
21. History of allergic response to heparin.
22. A positive hepatitis screen (includes subtypes B & C)
23. A positive test result for HIV antibody and / or syphilis (RPR/VDRL)
24. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Principal Investigator or Sub-Investigator, could contraindicate the patient’s participation in this study
25. Any other condition 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
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
An Open list of random numbers
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To characterize the pharmacokinetic profile of the sponsor’s test formulation (Capecitabine Tablets 500 mg, Manufactured by Cadila Heathcare Limited, India) relative to that of reference formulation (XELODA® 500 mg tablets, Manufactured by Genentech USA Inc. USA) in patients of Metastatic Breast Cancer, Duke’s C Colon Cancer or Metastatic Colorectal Cancer under fed condition and to assess the bioequivalence.
Time points are 30 minutes prior to drug dosing and at 0.25hr, 0.50hr, 1hr, 1.5hr, 2hr, 2.5hr, 3hr, 4hr, 5hr, 6hr, 8hr and 10 hours post-dose.
Secondary Outcome
Outcome
TimePoints
To monitor the safety of the patients
30 minutes prior to drug dosing and 0.25, 0.50, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 10 hours post-dose.
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 a multi-center, open-label, single-dose, three-period, randomized, two-treatment, crossover study to investigate the bioequivalence of a single formulation of Cadila Healthcar’s Capecitabine Tablets, 500 mg compared to the Genentech’s Xeloda® Tablets, 500 mg.
The single-dose pharmacokinetics of capecitabine will be characterized in fifty-four (54) adult, male and not of childbearing potential female volunteers with metastatic breast cancer, Duke’s C colon cancer after complete resection, or metastatic colorectal cancer for whom the drug is indicated either alone or in combination with another drug.
Each patient will receive a capecitabine dose of 1250 mg/m2 dose in the morning under fed conditions.The dose will be comprised of multiples of the 500 mg tablet.In order to determine the pharmacokinetic parameter (CPEAK and AUC) intra-patient variability for Xeloda®, each patient will receive Xeloda® twice during the course of the study.
Subjects will be housed at least 11 hours prior to the first dose of investigational product until at least 10 hours after the final dose of investigational product.Blood samples (1×4 mL except predose 8 mL) will be collected in K2 EDTA tubes 30 minutes prior to drug dosing and 0.25, 0.50, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 10hours post-dose. Patients will receive their regularly scheduled dose of capecitabine 12 hours after the morning dose of investigational product. Patients will receive a single dose of the test product and two doses of the reference product between Cycle Day 2 and Cycle Day 13 (inclusive) of a single treatment cycle.
In between investigational (test/reference) product administration, the patient will continue to receive their standard dosing regimen medication.
The collected blood samples will be cooled in an ice bath or sample cooling rack (e.g. Kryorack) and centrifuged under refrigeration as soon as possible.
Plasma will be extracted, divided into two (2) equal aliquots, and stored in suitably labeled tubes at −20°C ± 10°C or colder until shipment to the central storage site. Samples will be stored in freezer at -70oC+ 20oC at analytical site until analyzed. For each subject the duration of the study will be 3 to 11 days.