CTRI/2012/01/002386 [Registered on: 30/01/2012] Trial Registered Prospectively
Last Modified On:
24/11/2018
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A Bioequivalence study of two formulations of Capecitabine tablets in breast cancer and colorectal cancer patients.
Scientific Title of Study
A multicentre, randomized, open label, two-period, two-treatment, two-way crossover, bioequivalence study comparing Capecitabine Tablets USP 500 mg (Manufactured by: Intas Pharmaceuticals Ltd, India) to the reference listed drug Xeloda® (Capecitabine) Tablets 500 mg (Distributed by: Roche Chemical and Pharmaceutical Products SA, Brazil) in Metastatic Breast Cancer or Colorectal Cancer patients under fed condition
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
725-10
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Rajesh CN
Designation
Project Manger
Affiliation
Lambda Therapeutic Research Pvt Ltd
Address
Lambda Therapeutic Research Pvt Ltd,Plot No. 38, Near Silver Oak Club,S G Highway, Gota,Ahmedabad - 380061.
Gujarat, India
NIL Ahmadabad GUJARAT 380061 India
Phone
07940202051
Fax
Email
rajeshcn@lambda-cro.com
Details of Contact Person Scientific Query
Name
Dr Praveen Shetty
Designation
Asst Maanger, Medical Affairs
Affiliation
Lambda Therapeutic Research Pvt Ltd
Address
Lambda Therapeutic Research Pvt Ltd,Plot No. 38, Near Silver Oak Club,S G Highway, Gota,Ahmedabad - 380061.
Gujarat, India
NIL Ahmadabad GUJARAT 380061 India
Phone
07940202098
Fax
07940202021
Email
praveenshetty@lambda-cro.com
Details of Contact Person Public Query
Name
Dr Praveen Shetty
Designation
Asst Maanger, Medical Affairs
Affiliation
Lambda Therapeutic Research Pvt Ltd
Address
Lambda Therapeutic Research Pvt Ltd,Plot No. 38, Near Silver Oak Club,S G Highway, Gota,Ahmedabad - 380061.
Gujarat, India
NIL
GUJARAT 380061 India
Phone
07940202098
Fax
07940202021
Email
praveenshetty@lambda-cro.com
Source of Monetary or Material Support
Intas Pharmaceuticals Ltd
Primary Sponsor
Name
Intas Pharmaceuticals Ltd
Address
2nd Floor, Chinubhai Center, Ashram Road, Ahmedabad 380-009, Gujarat, India.
Bharat cancer hospital & reserch Institute (Man. By: Shri Bhartimaiya memorial Foundation)
Room No. 22C, OPD Department, Bharat Cancer Hospital & reserch Institute (Man. By: Shri Bhartimaiya memorial Foundation), Manavdaya trust complex, Surat-Bardoli road, Saroli, Surat- 395010
Surat GUJARAT
09909918887
tanveermaksud@yahoo.com
Dr Suresh Attili
Bibi General Hospital and Cancer Centre
Bibi General Hospital and Cancer Centre,16-3-991/1/C, Government printing press road
Malak Pet-500024 Hyderabad ANDHRA PRADESH
9246243034
sureshattili@yahoo.com
Dr Smita Gupte
Cancer Clinic & Nursing Home
Cancer Clinic & Nursing Home, Block 4B, Hyatt Medicare, Plot No. 12/2, Dr. N. B. Khare Marg, Dhantoli- 440012 Nagpur MAHARASHTRA
9373107176
Smita_gupte@rediffmail.com
Dr Gopichand
City Cancer Centre
"Department of Clinical research, City Cancer Centre
# 33-25-33, Ch. Venkata Krishynna Street, Suryaraopet,
Vijayawada – 520002
Vijayawada – 520002, Vizianagaram ANDHRA PRADESH
9885256059
mgopichand@yahoo.com
Dr SM karandikaR
Galaxy Care Hospital, Galaxy Care Laparoscopy institute
Galaxy Care Hospital, Galaxy Care Laparoscopy institute, 25-A karve road-411004 Pune MAHARASHTRA
9890281963
skaran44@gmail.com
Dr Niraj Bhatt
Kailash cancer hospital & medical Centre
Room No. 2, Chemotherapy Dept, Kailash cancer hospital & medical Centre, Muniseva Ashram, Gujarat, Ta: Waghodiya, Vadodara-391760, Gujarat.
Vadodara GUJARAT
09925581480
medonc12@gmail.com
Dr Yathish Kumar HM
Karnataka cancer hospital & research centre
"Department of Cliinical research
Karnataka Cancer Hospital & Research Centre No:99, J.B Karal Nandhini Layout Krishnanandannagar, Banglore-560096 Bangalore KARNATAKA
91-9880462912
dryathish@hotmail.com
Dr SPSrivastav
lions Cancer Detection Centre
"Medical Director, lions Cancer Detection Centre , New Civil Hospital Campus,
Majura Gate, Surat
Mob: 09824196710
Surat GUJARAT
09824196710
liononco@gmail.com
Dr Nagesh Madnoorkar
Magnum heart institute
Consulting No. 2, Magnum heart Institute, Patil Lane No. 1, Opp. Vasanti Market, Canada corner, Nashik
Nashik MAHARASHTRA
9822353986
nageshmadneerkar@gmail.com
Dr J K Singh
Mahavir Cancer Sansthan
Mahavir Cancer Sansthan, Phulwarisharif– 801505 Patna BIHAR
9431021001
drjksingh147@hotmail.com
Dr Kirushna Kumar
Meenakshi Mission Hospital & Research Centre
01st floor, Department of Clinical Research, Meenakshi Mission Hospital & Research Centre, Lake Area, Melur Road, Madurai- 625107, Tamilnadu
Madurai TAMIL NADU
09842113003
drkskk@yahoo.com
Dr Rakesh Neve
Nandadeep Multispeciality Hospital,
Dr. Rakesh Neve, 1st floor, Nandadeep Multispeciality Hospital, 1195/1, F.C.Road, Shivajinagar, Pune- 411003
Pune MAHARASHTRA
9881143140
rakesh.neve@gmail.com
Dr Tapan Saikia
Prince Aly Khan Hospital
Prince Aly Khan Hospital, Aya Hall, Nesbit Road, Mazgaon-400010 Mumbai MAHARASHTRA
9819330553
tapan.saikia@gmail.com
Dr Milindkumar Wankhede
Shreeji Multispeciality Hospital & Clinical research centre,
Consultant Surgical Oncologist, Oncology Department, Dr. Milindkumar Wankhede, Shreeji Multispeciality Hospital & Clinical research centre, 2nd Floor, Castle Rock, Opp. Vishwas Bank, Near Canada corner Signal, Nashik
Nashik MAHARASHTRA
9970283245
drmilindwankhede@gmail.com
Dr Krishna Prasad
Vinayaka Hospital and Research Center
Vinayaka Hospital and Research Center, Karangalpady-575003 Dakshina Kannada KARNATAKA
(1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Capecitabine Tablets USP 500 mg
Each film -coated tablet contains: Capecitabine USP 500 mg Manufactured by: Intas Pharmaceuticals Ltd, India.
The recommended dose of XELODA® is 1250 mg/m2 administered orally twice daily (morning and evening; equivalent to 2500 mg/m2 total daily dose) for 2 weeks followed by a 1-week rest period given as 3 week cycles.
In current study, Test and Reference formulation of Capecitabine Tablets USP 500 mg will be administered as a single dose as multiples of 500mg on Day 1 and Day 2 morning dose as per randomization schedule. The evening dose on day 1 and day 2 will be locally approved and marketed capecitabine Tablets 500 mg. Locally approved and marketed Capecitabine will also be provided for the remaining treatment cycle/s.
Comparator Agent
Xeloda® (capecitabine) Tablets 500 mg
Each tablet contains: Capecitabine 500 mg
Distributed by: Roche Chemical and Pharmaceutical Products SA, Brazil
The recommended dose of XELODA® is 1250 mg/m2 administered orally twice daily (morning and evening; equivalent to 2500 mg/m2 total daily dose) for 2 weeks followed by a 1-week rest period given as 3 week cycles. In current study, Test and Reference formulation of Capecitabine Tablets USP 500 mg will be administered as a single dose as multiples of 500mg on Day 1 and Day 2 morning dose as per randomization schedule. The evening dose on day 1 and day 2 will be locally approved and marketed capecitabine Tablets 500 mg. Locally approved and marketed Capecitabine will also be provided for the remaining treatment cycle/s.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
79.00 Year(s)
Gender
Both
Details
Patients should have their BSA (as per the DuBois formula) between 1.26-1.91 m2 (Both inclusive
Pateints with metastatic breast cancer, colorectal cancer
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Patient with adequate bone marrow, renal and hepatic function.
Adequate Cardiac function (left ventricular ejection fraction [LVEF] ≥50%)
Patient should have recovered from any toxic effects of previous chemotherapy as judged by the Investigator
ExclusionCriteria
Details
Prior unanticipated severe reaction to fluoropyrimidine therapy, or known sensitivity to 5-fluorouracil, or known DPD (Dihydropyrimidine Dehydrogenase) deficiency.
Pregnant or breast-feeding female
Any of the following cardiac conditions:
Unstable angina
Myocardial infarction within the past 6 months
NYHA (New York State Heart Association) class II-IV heart failure
Severe uncontrolled ventricular arrhythmias
Clinically significant pericardial disease
Electrocardiographic evidence of acute ischemic or active conduction system abnormalities
Any other cardiac illness that could lead to a safety risk to the patient in case of enrolment in the study
History of drug/alcohol addiction
Known brain metastasis
Patient having abnormal serum calcium level at screening visit which as judged by Investigator could lead to safety risk to the patient upon participation in the trial or could interfere with the conduct of the trial.
Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by NCI CTCAE criteria.
A positive hepatitis screen including hepatitis B surface antigen, HCV or HAV (IgM) antibodies
Patients with HIV infection.
Positive for Drug of abuse test
Method of Generating Random Sequence
Other
Method of Concealment
Other
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To characterise the pharmacokinetic profile of the sponsor’s test formulation [Capecitabine Tablets USP 500 mg (Manufactured by: Intas Pharmaceuticals Ltd, India)] relative to that of reference formulation [Xeloda®(capecitabine) Tablets 500 mg (Distributed by: Roche Laboratories Inc., Brazil)] in patients of Metastatic Breast Cancer or Colorectal Cancer under fed condition and to assess the bioequivalence.
NIL
Secondary Outcome
Outcome
TimePoints
To monitor the safety of the patients, who are exposed to the Investigational Medicinal Product.
NIL
Target Sample Size
Total Sample Size="104" Sample Size from India="104" 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 is A multicentre, randomized, open label, two-period, two-treatment, two-way crossover, bioequivalence study comparing Capecitabine Tablets USP 500 mg (Manufactured by:Intas Pharmaceuticals Ltd, India) to the reference listed drug Xeloda® (Capecitabine) Tablets 500 mg (Distributed by:Roche Chemical and PharmaceuticalProductsSA, Brazil)in Metastatic Breast Cancer or Colorectal Cancer patients under fed condition.
Background
XELODA® (Capecitabine) is a fluoropyrimidine carbamate with antineoplastic activity. It is an orally administered systemic prodrug of 5’-deoxy-5-fluorouridine (5’-DFUR) which is converted to 5-fluorouracil. The chemical name for Capecitabine is 5’-deoxy-5-fluoro-N-[(pentyloxy) carbonyl]-cytidine
Rationale For Study Design
Capecitabine 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 on patients of Metastatic Breast Cancer or Colorectal cancer, who in the opinion of their treating physicians are candidates for Capecitabine therapy. Moreover, this is also in agreement with the current draft guidance on Capecitabine by OGD, USFDA.
The recommended dose of XELODA® is 1250 mg/m2 administered orally twice daily (morning and evening; equivalent to 2500 mg/m2 total daily dose) for 2 weeks followed by a 1-week rest period given as 3 week cycles. The dose of Capecitabine can be reduced in case of toxicity as per the Prescribing information of XELODA®.
The elimination half-life of Capecitabine is about ¾ of an hour.
In current study, Test and Reference formulation of Capecitabine Tablets USP 500 mg will be administered as a single dose as multiples of 500 mg on Day 1 and Day 2 morning dose as per randomization schedule. The evening dose on day 1 and day 2 will be locally approved and marketed capecitabine Tablets 500 mg. Locally approved and marketed Capecitabine will also be provided for the remaining treatment cycle/s.
Objective
Primary Objective:
To characterise the pharmacokinetic profile of the sponsor’s test formulation [Capecitabine Tablets USP 500 mg (Manufactured by: Intas Pharmaceuticals Ltd, India)] relative to that of reference formulation [Xeloda®(capecitabine) Tablets 500 mg (Distributed by:Roche Laboratories Inc., Brazil)] in patients of Metastatic Breast Cancer or Colorectal Cancer under fed condition and to assess the bioequivalence.
Secondary Objective:
To monitor the safety of the patients, who are exposed to the Investigational Medicinal Product.