CTRI/2020/10/028417 [Registered on: 15/10/2020] Trial Registered Prospectively
Last Modified On:
18/10/2021
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Randomized, Crossover Trial
Public Title of Study
A study of Capecitabine 200 mg/ ml with Xeloda 500 mg (Capecitabine) at a dose of 2000 mg in adult human cancer patients under fed conditions.
Scientific Title of Study
An open label, multicenter, balanced, randomized, two-treatment, four-period, two-sequence, full replicate crossover, single dose, comparative bioavailability study of Capecitabine 200 mg/ ml oral suspension of Shilpa Medicare Limited, India with Xeloda 500 mg Film-Coated Tablets (Capecitabine) marketed by Roche Registration Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom at a dose of 2000 mg in adult human cancer patients under fed conditions.
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Sandeep Singh
Designation
Vice President - Clinical Operations
Affiliation
CBCC Global Research LLP
Address
Clinical Operations Department, Room Number 2, East Wing, Second Floor Skoda House, Opposite L. J Campus, S. G. Highway, Sarkhej, Ahmedabad – 382210, India.
Ahmadabad GUJARAT 382210 India
Phone
9637555304
Fax
9726434204
Email
sandeep.singh@cbccusa.com
Details of Contact Person Scientific Query
Name
Dr Sandeep Singh
Designation
Vice President - Clinical Operations
Affiliation
CBCC Global Research LLP
Address
Clinical Operations Department, Room Number 2, East Wing, Second Floor Skoda House, Opposite L. J Campus, S. G. Highway, Sarkhej, Ahmedabad – 382210, India.
GUJARAT 382210 India
Phone
9637555304
Fax
9726434204
Email
sandeep.singh@cbccusa.com
Details of Contact Person Public Query
Name
Dr Sandeep Singh
Designation
Vice President - Clinical Operations
Affiliation
CBCC Global Research LLP
Address
Clinical Operations Department, Room Number 2, East Wing, Second Floor Skoda House, Opposite L. J Campus, S. G. Highway, Sarkhej, Ahmedabad – 382210, India.
Institutional Ethics Committee Erode Cancer Center
Approved
Institutional Ethics Committee, Kailash cancer Hospital and Research center
Approved
Kiran Hospital Ethics Committee
Approved
Manavata Clinical Research Institute Ethics Committee
Approved
MNJ Institute of Oncology and Regional Cancer Centre Institutional Ethics Committee
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 200 mg/ ml oral suspension of Shilpa Medicare Limited, India
Dose: Dose as per Dubois formula 3300-4600mg daily dose
Frequency: Twice a Day
Route of Administration: Oral
Duration of Therapy: 21 Days
Comparator Agent
Xeloda 500 mg Film-Coated Tablets (Capecitabine
Dose: Dose as per Dubois formula 3300-4600mg daily dose Frequency: Twice a Day Route of Administration: Oral Duration of Therapy: 21 Days
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
The patients will be considered eligible for the study based on the following criteria:
1. Willing and able to provide voluntary informed consent and able to comply with protocol requirements
2. Male or Female aged 18 to 65 years both inclusive having body mass index BMI at least 17.00 calculated as weight in kg per height in m2.
3. Patients having Body Surface Area between 1.27 to 1.92 m2 both inclusive measured as per the Dubois formula.
4. Patients with histopathologically or cytologically confirmed colon or colorectal or breast cancer.
5. Patients with Dukes’ C colon cancer who have undergone complete resection of the primary tumor and when treatment with fluoropyrimidine therapy alone is preferred Or Patients with metastatic colorectal carcinoma in whom treatment with fluoropyrimidine therapy alone is preferred. Or Patients with locally advanced or metastatic breast cancer, after failure of taxanes and an anthracycline-containing chemotherapy regimen or for whom further anthracycline therapy is not indicated.
6. Patients requiring a daily dose of Capecitabine monotherapy and stabilized at least one cycle of Capecitabine chemotherapy i.e. twice daily at a dose of 1250 mg per m2 for 2 weeks followed by a one week rest period.
7. Cardiac ejection fraction greater or equal to 50 Percent by echocardiogram ECHO at screening.
8. Eastern Cooperative Oncology Group ECOG performance status less than or equal to 2.
9. Acceptable hematology status
a. Hemoglobin greater or equal to 9 g per dL
b. Absolute neutrophil count ANC greater or equal to 1500 cells per mm3
c. Platelet count greater or equal to 100,000 cells per mm3
10. Acceptable liver function:
a. Alanine aminotransferase ALT less than or equal to 2.5 X ULN
b. Aspartate aminotransferase AST less than or equal to 2.5 X ULN
c. Bilirubin less than or equal to 1.5 X ULN
d. Alkaline phosphatase less than or equal to 2.5 X ULN
11. Patients with creatinine clearance greater than 60 mL per minute.
12. Patients with life expectancy of at least 3 months at the time of enrolment.
13. Non-smokers and non-alcoholics
14. Male patients must agree to use an effective method of contraception from screening, during study and for at least 03 months after treatment discontinuation.
15. Female patients with negative serum pregnancy test at screening and negative urine pregnancy test on Day 0.
16. Women of child bearing potential, defined as women physiologically capable of becoming pregnant, unless they are using effective method of contraception during dosing of the investigational product practicing two acceptable methods of contraception.
Acceptable methods of contraception are:
a. Oral or parenteral injection, patch or implant) hormonal contraception which has been used continuously for at least one month prior to the first dose of study medication
b. Intrauterine device IUD or intrauterine system IUD or IUS
c. Double barrier method of contraception Condom and occlusive cap or condom and spermicidal agent)
d. Male sterilization at least 6 months prior to the screening, should be the sole male partner for that patient
e. Female sterilization surgical bilateral oophorectomy or tubal ligation within at least 6 weeks prior to study participation
f. Total abstinence, partial abstinence is not acceptable.
17. No history of addiction to any recreational drug or drug dependence.
ExclusionCriteria
Details
The patients will be excluded from the study based on the following criteria:
1. Known hypersensitivity or contraindication to fluoropyrimidine therapy or to any of the components of investigational product.
2. Known hypersensitivity or contraindication to Ondansetron.
3. Known CNS metastasis.
4. Known deficiency of dihydropyrimidine dehydrogenase (DPD)
5. Patient with history of cardiac disease
6. Major surgical procedure (including periodontal) within 28 days of first dose of Investigational Product.
7. Surgical or other non-healing wounds.
8. Patients with positive serology for Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV).
9. Patients with positive urine screen for drugs of abuse.
10. History of other malignancies in the last 5 years (except in situ cancer or basal or squamous cell skin cancer).
11. Has not recovered to Grade 0 or 1 toxicity from previous anticancer treatments or previous investigational agents. Exceptions are alopecia (any grade is acceptable), haemoglobin greater or equal to 9.0 g/dL, fatigue (Grade 2 is acceptable), and peripheral neuropathy (stable Grade 2 is acceptable) (As per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], V5.0)
12. Participation in any clinical study within 90 days prior to receiving the first dose of Investigational Product.
13. Loss of blood greater or equal to 350 mL within 90 days prior to receiving the first dose of investigational product for the current study.
14. Patients taking or scheduled to receive any of the Cytochrome P450 2C9 substrates (As per appendix B)
15. Any other medical condition or uncontrolled systemic disease (e.g. cardiovascular disease, hypertension, diabetes mellitus etc.) that, in the opinion of the Investigator, may make it undesirable for the patient to participate in the study including but not limited to cirrhosis or psychiatric illness/social situations that would limit adherence to study requirements.
16. Lactating women.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Pre-numbered or coded identical Containers
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To compare and evaluate bioavailability of Capecitabine 200 mg/ ml oral suspension of Shilpa Medicare Limited, India and Xeloda 500 mg Film-Coated Tablets (Capecitabine) marketed by Roche Registration Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom at a dose of 2000 mg in adult human cancer patients under fed conditions.
A total of eighteen (18) blood samples of 3.0 mL each will be collected for PK analysis in each period of the study. A total of 72 blood samples will be collected during the study. Sample 1:Pre-dose blood sample (00.00)-within 1.00 hour prior to dosing,2- 0.17Hrs ,3- 00.33 Hrs,4-00.50Hrs ,5-00.67Hrs, 6-01.00Hrs,7-01.25Hrs ,8-01.50Hrs ,9-01.75Hrs,10-02.00Hrs,11-02.33Hrs,12-02.67Hrs,13-03.00Hrs,14-03.50Hrs,15-04.00Hrs,16-05.00Hrs,17-06.00Hrs ,18-08.00Hrs(± 02 minutes)
Secondary Outcome
Outcome
TimePoints
To monitor the adverse events and to ensure the safety of patients.
A total of eighteen (18) blood samples of 3.0 mL each will be collected for PK analysis in each period of the study. A total of 72 blood samples will be collected during the study. Sample 1:Pre-dose blood sample (00.00)-within 1.00 hour prior to dosing,2- 0.17Hrs ,3- 00.33 Hrs,4-00.50Hrs ,5-00.67Hrs, 6-01.00Hrs,7-01.25Hrs ,8-01.50Hrs ,9-01.75Hrs,10-02.00Hrs,11-02.33Hrs,12-02.67Hrs,13-03.00Hrs,14-03.50Hrs,15-04.00Hrs,16-05.00Hrs,17-06.00Hrs ,18-08.00Hrs(± 02 minutes)
Target Sample Size
Total Sample Size="32" Sample Size from India="32" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The Study is an open label, multicenter, balanced, randomized, two-treatment, four-period, two-sequence, full replicate crossover, single dose, comparative bioavailability study of Capecitabine 200 mg/ ml oral suspension of Shilpa Medicare Limited, India with Xeloda 500 mg Film-Coated Tablets (Capecitabine) marketed by Roche Registration Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom at a dose of 2000 mg in adult human cancer patients under fed conditions.
Primary Objective: To compare and evaluate bioavailability of Capecitabine 200 mg/ ml oral suspension of Shilpa Medicare Limited, India and Xeloda 500mg Film-Coated Tablets (Capecitabine) marketed by Roche Registration Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom at a dose of 2000 mg in adult human cancer patients under fed conditions.
Secondary Objective: To monitor the adverse events and to ensure the safety of patients.