CTRI/2019/10/021793 [Registered on: 25/10/2019] Trial Registered Prospectively
Last Modified On:
01/11/2019
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A study comparing capecitabine oral granules 500 mg per packet to capecitabine tablets 500 mg in patients with breast cancer or colorectal cancer
Scientific Title of Study
A multicenter, open label, balanced, randomized, two-treatment, three-period, three sequence, single oral dose, partial replicate, cross-over, bioequivalence study comparing test formulation of capecitabine oral granules 500 mg per packet (Manufactured by: Intas Pharmaceuticals Ltd, India) to the reference formulation of Xeloda® (capecitabine) tablets 500 mg (Distributed by: Genentech USA, Inc., A member of the Roche group, 1 DNA Way, South San Francisco, CA 94080-4990) in patients with metastatic breast cancer or metastatic colorectal cancer, already receiving a stable twice-daily dose of 1250 mg/m2, equivalent to 2500 mg/m2 total daily dose under fed condition.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
1038-18, Version no. 2.0, Date: 22 May 2019
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Prashant Modi
Designation
General Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Department of Project Management & Regulatory
Affairs, Plot No. 38, Survey No. 388 Near Silver Oak Club, S. G.
Highway, Gota Ahmadabad GUJARAT 382481 India
Phone
07940202375
Fax
07940202021
Email
prashantmodi@lambda-cro.com
Details of Contact Person Scientific Query
Name
Dr Naman Shah
Designation
General Manager
Affiliation
Lambda Therapeutic Research Ltd.
Address
Lambda House, Department of CTM Medical Services, Plot No. 38, Survey No. 388 Near Silver Oak Club, S. G. Highway, Gota Ahmadabad GUJARAT 382481 India
Phone
07940202389
Fax
07940202021
Email
namanshah@lambda-cro.com
Details of Contact Person Public Query
Name
Mr Prashant Modi
Designation
General Manager
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Department of Project Management & Regulatory Affairs, Plot No. 38, Survey No. 388 Near Silver Oak Club, S. G.
Highway, Gota Ahmadabad GUJARAT 382481 India
Phone
07940202375
Fax
07940202021
Email
prashantmodi@lambda-cro.com
Source of Monetary or Material Support
Intas Pharmaceuticals Ltd,
Corporate House, Nr. Sola Bridge, S.G. Highway, Thaltej, Ahmedabad –
380054, Gujarat, India
Tel. No. 07939837000
Primary Sponsor
Name
Intas Pharmaceuticals Ltd
Address
Corporate House, Nr. Sola Bridge, S.G. Highway, Thaltej, Ahmedabad – 380054, Gujarat, India Tel. No. 07939837000
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NA
NA
Countries of Recruitment
India
Sites of Study
No of Sites = 5
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr KVelavan
Erode Cancer Centre Private Ltd.
1/393, Department of Clinical Research, Room No. NA, Velavan Nagarm, Perundurai Road, Thindal-638012 Erode TAMIL NADU
9842334222
kvels@rediffmail.com
Dr Sushil Meshram
Government Medical College and Hospital.
Department of Radiation Therapy and Oncology, Room No. NA, Near Hanuman Nagar-440003 Nagpur MAHARASHTRA
7028966535
drsushilonco@gmail.com
Dr Rajnish Nagarkar
HCG Manvata Cancer Centre
Behind Shivang Auto, Department of Clinical Research, Room No. NA, Mumbai Naka-422001, Nashik MAHARASHTRA
9823061929
drraj@manavatacancercentre.com
Dr Rohan Bhise
KLES Dr. Prabhakar Kore Hospital & MRC
Department of Clinical Research, Room No. NA, Nehrunagar, Belagavi-590010 Belgaum KARNATAKA
9448866712
rohanbhise30@gmail.com
Dr Prakash SS
KR Medical College
K.R. Hospital, Department of Clinical Research, Room No. NA, Mysore Medical College & Research Institute-570001 Mysore KARNATAKA
Institute Ethics Committee Erode Cancer Centre, Dr. K.Velavan
Approved
Institutional Ethics Committee Department of Pharmacology, Government Medical College, Dr. Sushil Meshram
Submittted/Under Review
Institutional Ethics committee, KAHER, Dr. Rohan Bhise
Submittted/Under Review
Institutional Ethics Committee, Mysore Medical College & Research Institute and associated hospital, Dr. Prakash S.S.
Submittted/Under Review
Manavata Clincal Research Institute Ethics Committee, Dr Rajnish Nagarkar
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Capecitabine oral granules 500 mg per packet of Intas Pharmaceuticals Limited, India
Dose: single dose as multiples of 500 mg ; Frequency: single dose on day 1, day 2 and day 3 ; Mode of Administration: oral ; Duration of treatment: 3 days
Comparator Agent
Xeloda® (capecitabine) tablets 500 mg, Distributed by: Genentech USA, Inc., A member of the Roche group
Dose: single dose as multiples of 500 mg ; Frequency: single dose on day 1, day 2 and day 3 ; Mode of Administration: oral ; Duration of treatment: 3 days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Patient and /or LAR willing to give written informed consent for participation in the trial.
2. Male or Female ≥18 years and ≤ 65 years of age and having a Body Mass Index (BMI) at least 17 calculated as weight in kg / height in m2.
3. Patients must have/have had histopathologically /cytologically confirmed breast cancer or colorectal cancer.
4. Patients with
a. Dukes C colon cancer patients who have undergone complete resection of the primary tumour when treatment with fluoropyrimidine therapy alone is preferred. OR
b. Metastatic colorectal carcinoma when treatment with fluoropyrimidine therapy alone is preferred. OR
c. Metastatic breast cancer resistant to chemotherapy regimens with paclitaxel and anthracycline-resistant or paclitaxel for patients in whom additional therapy with an anthracycline is not indicated.
5. 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.
6. Patients should have their BSA between 1.26-1.91 (Both inclusive).
7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
8. Patient with adequate bone marrow, renal and hepatic function.
9. Adequate cardiac function (left ventricular ejection fraction [LVEF] ≥50%).
10. Patient should have recovered from any toxic effects of previous chemotherapy as
judged by the Investigator.
11. Patients with life expectancy of at least 3 months (as per the Investigators
discretion).
12. Able to comply with study requirement in opinion of Investigator.
13. Able to give written informed consent for participation in the trial.
14. In case of female patient the serum pregnancy test at screening visit and urine
pregnancy test at day 0 must be negative.
15. 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 4 weeks prior to study drug administration, during study and up to 180 days after the last dose of study drug. Cessation of birth control after this point should be discussed with a responsible physician.
16. In case of male patients: Either partner or patient must use an effective method of
avoiding pregnancy for at least 4 weeks prior to study drug administration, during
study and up to 90 days after the last dose of study drug. Cessation of birth control
after this point should be discussed with a responsible physician.
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:
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.
4. History of drug/alcohol addiction.
5. Known brain metastasis.
6. Pre-existing motor or sensory neurotoxicity of a severity ≥ grade 2 by NCI CTCAE criteria.
7. A positive hepatitis screen including hepatitis B surface antigen and HCV antibodies.
8. Patients with HIV infection.
9. Patients found positive on urine scan for drugs of abuse and/or breath test for alcohol consumption at screening or baseline.
10. The receipt of an investigational medicinal product or participation in other drug research study within a period of 30 days (or 5 half-lives, whichever is longer) prior to the first dose of investigational medicinal product for the current study.
11. Any other condition that, in the investigators judgment, might increase the risk to the patient or decrease the chance of obtaining satisfactory data needed to achieve
the objectives of the study.
12. Abnormal baseline findings considered by the investigator to indicate conditions that might affect study endpoints.
13. Donation of blood (1 unit or 350 ml) within 90 days prior to receiving the first dose of investigational medicinal product for the current study.
14. Known, existing uncontrolled coagulopathy.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To characterise the pharmacokinetic profile of the sponsors test formulation
[capecitabine oral granules 500 mg per packet (Manufactured by Intas Pharmaceuticals Ltd, India)] relative to that of reference formulation [Xeloda® (capecitabine) tablets 500 mg (Distributed by: Genentech USA, Inc., A member of the Roche group, 1 DNA Way, South san Francisco, CA 94080-4990)] in patients of metastatic breast cancer or metastatic colorectal cancer under fed condition and to assess the bioequivalence.
Total Sample Size="15" Sample Size from India="15" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
N/A
Date of First Enrollment (India)
04/11/2019
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="0" Months="10" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
None Yet
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
The present study is a bioequivalence study wherein the relative bioavailability of test formulation [capecitabine oral granules 500 mg (Manufactured by: Intas Pharmaceuticals Limited, India)] will be compared with reference formulation [Xeloda® (capecitabine) tablets 500 mg (Distributed by: Genentech USA, Inc., A member of the Roche group, 1 DNA Way, South san Francisco, CA 94080-4990] in patients with metastatic breast cancer or colorectal cancer under fed condition. 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®. In current study, test formulation of capecitabine oral granules 500 mg and reference formulation of capecitabine tablets 500 mg will be administered as a single dose as multiples of 500 mg on day 1, day 2 and day 3 morning dose as per randomization schedule. The evening dose on day 1, day 2 and day 3 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.