| CTRI Number |
CTRI/2011/05/001751 [Registered on: 20/05/2011] Trial Registered Prospectively |
| Last Modified On: |
17/11/2018 |
| Post Graduate Thesis |
No |
| Type of Trial |
BA/BE |
|
Type of Study
|
|
| Study Design |
Randomized, Crossover Trial |
|
Public Title of Study
|
To test the similarity of two formulation of Capecitabine in Metastatic Breast Cancer or Colorectal Cancer patients |
|
Scientific Title of Study
|
A multicentre, randomized, double blind, two-period, two-treatment, two-way crossover, bioequivalence study comparing Capecitabine Tablets USP 500 mg (Manufactured by: Intas Pharmaceuticals limited, India) to the reference listed drug Xeloda® (Capecitabine) Tablets 500 mg (Distributed by: Hoffmann-La Roche Limited., Mississauga ON L5N 6L7, Canada) in Metastatic Breast Cancer or Colorectal Cancer patients under fed condition |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 018-11 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Mr Rajesh CN |
| Designation |
Overall Trial Cordinator |
| Affiliation |
|
| Address |
Lambda Therapeutic Research Limited
Near Gujarat High Court, S.G. Highway, Gota, Ahmedabad
NIL
Ahmadabad
GUJARAT
380061
India |
| Phone |
079-40202051 |
| Fax |
079-40202022 |
| Email |
rajeshcn@lambda-cro.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Praveen Shetty |
| Designation |
Asst- Manager |
| Affiliation |
|
| Address |
Lambda Therapeutic Research Limited
Near Gujarat High Court, S.G. Highway, Gota, Ahmedabad
Ahmadabad
GUJARAT
380061
India |
| Phone |
079-40202098 |
| Fax |
079-40202022 |
| Email |
praveenshetty@lambda-cro.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Praveen Shetty |
| Designation |
Asst- Manager |
| Affiliation |
|
| Address |
Lambda Therapeutic Research Limited
Near Gujarat High Court, S.G. Highway, Gota, Ahmedabad
Ahmadabad
GUJARAT
380061
India |
| Phone |
079-40202098 |
| Fax |
079-40202022 |
| Email |
praveenshetty@lambda-cro.com |
|
|
Source of Monetary or Material Support
|
| Intas Pharmaceuticals limited |
|
|
Primary Sponsor
|
| Name |
Intas Pharmaceuticals limited |
| Address |
Intas Pharmaceuticals limited, 2nd Floor, Chinubhai Center, Ashram Road, Ahmedabad 380-009, Gujarat, India |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Lambda Therapeutic Research Ltd |
Near Gujarat High Court, S.G. Highway,
Gota, Ahmedabad 380061, India
|
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 8 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Tanveer Maksud |
Bharatb Cancer Hospital & Research Institute |
Manav Daya Trust, Surat-Bardoli road, Saroli,
Surat- 395010
Gujarat.
Surat
GUJARAT |
0261-2641000
tanveermaksud@yahoo.com |
| Dr Ajay Mehta |
Central India Cancer Research Institute |
Central India Cancer Research Institute
11, Shankar Nagar, West Highcourt Road,
Nagpur
440010
Maharastra
Nagpur
MAHARASHTRA |
0712-2520956
ajayonco@hotmail.com |
| Dr Gopichand |
City Cancer Centre |
City Cancer Centre
33-25-33,Venkata Krishynna street,Suryarao pet,
Vijayawada-520002
Andhra Pradesh.
Visakhapatnam
ANDHRA PRADESH |
9885260759
mgopichand@yahoo.com |
| Dr Venkatesan Srinivasan |
Dr. Kamakshi Memorial Hospital Pvt Ltd |
No:1 Radial Road, Pallikaranai,PIN: 600100
Chennai
TAMIL NADU |
09841022366
vsrinivasan09@gmail.com |
| Dr S P Shrivastav |
Lions Cancer Detection Centre |
Lions Cancer Detection Centre,
New Civil Hospital Campus, Majura Gate,
Surat -395001
Gujarat
Surat
GUJARAT |
0261-2241436
liononco@gmail.com |
| Dr Muralikrishnna |
Mahatma Gandhi Hospital & Research Institute |
Mahatma Gandhi Hospital & Research Institute,
C/O Vizag hospital & Cancer research centre pvt ltd,
1/T,M.V.P Colony,
Visakhapatnam-
530017.
Andhra Pradesh
Visakhapatnam
ANDHRA PRADESH |
0891-2551811
muralivoonna@yahoo.com |
| Dr Kirushna Kumar |
Meenakshi Mission Hospital & Research Centre |
Meenakshi Mission Hospital & Research Centre,
lake Area, Melur Road,
Madurai - 625107
TamilNadu.
Madurai
TAMIL NADU |
04522588741
drkskk@yahoo.com |
| Dr Rakesh Neve |
Nandadeep Multispeciality Hospital |
Nandadeep Multispeciality Hospital 1195/1, F.C. Road, Shivaji nagar PIN: 411005
Pune
MAHARASHTRA |
09881143140
rakesh.neve@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 8 |
| Name of Committee |
Approval Status |
| Central India Cancer Research Institute Ethics Committee,Nagpur |
Approved |
| Dr Kamakshi Memorial Hospitals Pvt Ltd., Medical Ethics Committee,Chennai |
Approved |
| Independent Ethics Committee,Ahmedabad |
Approved |
| Independent Ethics Committee,Ahmedabad |
Approved |
| Institutional Ethics Committee, City Cancer Canter ,Vijayawada |
Approved |
| Mahatma Gandhi Cancer Hospital & Research Centre, Institutional Review Board,Vishakhapatnam |
Approved |
| Meenakshi Mission Hospital & Research Centre,Ethical Review Board,Madurai |
Approved |
| Nandadeep Hospitals Independent Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C189||Malignant neoplasm of colon, unspecified, |
|
|
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 limited, India
|
Patients will be on an overnight fast for at least 10 hours prior to serving of a high-fat, high-calorie breakfast (approximately 800 to 1000 kilocalories) on the day of dosing. This meal should derive approximately 150, 250, and 500-600 kilocalories from protein, carbohydrate, and fat, respectively. Patients will be required to consume completely within 30 minutes prior to dosing in each period
Information on the amount of meal left and the time taken for consuming the meal will be recorded in the appropriate source notes. The actual time of meal distribution will also be recorded.
Capecitabine should be administered along with 150 mL of water within 30 minutes of serving the breakfast. On the morning of dosing, upto 250 ml of water may be permitted up to 2 hours before drug administration. 2 hours after drug administration, 250 ml of Xanthine-free fluids are permitted. No food should be allowed for at least 4 hours post-dose.
|
| Comparator Agent |
Xeloda® (capecitabine) Tablets 500 mg
Each tablet contains: Capecitabine 500 mg
Distributed by: Hoffmann-La Roche Limited., Mississauga ON L5N 6L7, Canada
|
Patients will be on an overnight fast for at least 10 hours prior to serving of a high-fat, high-calorie breakfast (approximately 800 to 1000 kilocalories) on the day of dosing. This meal should derive approximately 150, 250, and 500-600 kilocalories from protein, carbohydrate, and fat, respectively. Patients will be required to consume completely within 30 minutes prior to dosing in each period
Information on the amount of meal left and the time taken for consuming the meal will be recorded in the appropriate source notes. The actual time of meal distribution will also be recorded.
Capecitabine should be administered along with 150 mL of water within 30 minutes of serving the breakfast. On the morning of dosing, upto 250 ml of water may be permitted up to 2 hours before drug administration. 2 hours after drug administration, 250 ml of Xanthine-free fluids are permitted. No food should be allowed for at least 4 hours post-dose.
|
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
79.00 Year(s) |
| Gender |
Both |
| Details |
1. Male or Female18 to 79 years of age (both inclusive) of Indian nationality and having a Body Mass Index (BMI) at least 17 calculated as weight in kg / height in m2.
2. Patients must have histopathologically /cytologically confirmed breast cancer or
colorectal cancer.
3. Patients with Dukes C colon cancer who have undergone complete resection of the primary tumour, where treatment with Fluoropyrimidine therapy alone is indicated as adjuvant treatment.
Or
Firstline treatment of patients with metastatic colorectal cancer.
Or
Patient with advanced or metastatic breast cancer after failure of standard therapy including a Taxane, unless therapy with a Taxane is clinically contraindicated.
4. Patients who require a daily dose of Capecitabine monotherapy, who are stabilized on twice daily dosing for at least one cycle of chemotherapy before randomization and who are eligible to receive a dose of 2500 mg/m2/day.
5. Eastern Cooperative Oncology Group (ECOG) performance status.
6. Patient with adequate bone marrow, renal and hepatic function.
|
|
| ExclusionCriteria |
| Details |
1. Prior unanticipated severe reaction to Fluoropyrimidine therapy or known sensitivity to 5-fluorouracil or known DPD (Dihydropyrimidine Dehydrogenase) deficiency.
2. Pregnant or breast-feeding female
3. Any of the following cardiac conditions:
a. Unstable angina
b. Myocardial infarction within the past 6 months
c. NYHA (New York State Heart Association) class II-IV heart failure
d. Severe uncontrolled ventricular arrhythmias
e. Clinically significant pericardial disease
f. Electrocardiographic evidence of acute ischemic or active conduction system abnormalities
g. Any other cardiac illness that could lead to a safety risk to the patient in case of enrolment in the study
4. History of drug/alcohol addiction.
5. Known brain metastasis.
6. 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.
7. Pre-existing motor or sensory neurotoxicity of a severity grade 2 by NCI CTCAE criteria
|
|
|
Method of Generating Random Sequence
|
Other |
|
Method of Concealment
|
Other |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To characterize the pharmacokinetic profile of the sponsors test formulation [Capecitabine Tablets USP 500 mg (Manufactured by: Intas Pharmaceuticals limited, India)] relative to that of reference formulation [Xeloda (capecitabine) Tablets 500 mg (Distributed by: Hoffmann-La Roche Limited., Mississauga ON L5N 6L7, Canada)] 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="44"
Sample Size from India="44"
Final Enrollment numbers achieved (Total)= ""
Final Enrollment numbers achieved (India)="" |
|
Phase of Trial
|
N/A |
|
Date of First Enrollment (India)
|
30/05/2011 |
| Date of Study Completion (India) |
Date Missing |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="0"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
NO |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
This is a multicentre, randomized, double blind, two-period, two-treatment, two-way crossover, bioequivalence study comparing Capecitabine Tablets USP 500 mg (Manufactured by: Intas Pharmaceuticals limited, India) to the reference listed drug Xeloda® (capecitabine) Tablets 500 mg (Distributed by: Hoffmann-La Roche Limited., Mississauga ON L5N 6L7, Canada) in Metastatic Breast Cancer or Colorectal Cancer patients under fed condition
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.
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 morning dose as multiples of 500 mg on Day 1 and Day 2 as per randomization schedule. The evening dose on day 1 and day 2 will be locally approved or marketed capecitabineTablets 500 mg which will be given at least 11 hours post morning dose. Locally approved or marketed Capecitabine will also be provided for the remainder treatment cycle/s (including the 1st cycle) as compassionate medication.
P.S.: If the patient screen fails after 1st cycle of compassionate medication, then he/she would not be eligible for compassionate medications of the remaining cycles.
Primary Objective:
To characterize the pharmacokinetic profile of the sponsor’s test formulation [Capecitabine Tablets USP 500 mg (Manufactured by: Intas Pharmaceuticals limited, India)] relative to that of reference formulation [Xeloda® (capecitabine) Tablets 500 mg (Distributed by: Hoffmann-La Roche Limited., Mississauga ON L5N 6L7, Canada)] 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
|