To test the similarity of two formulation of Capecitabine in Metastatic Breast Cancer or Colorectal Cancer patients

Completed

Conditions: Malignant neoplasm of colon, unspecified,

Registration Number: CTRI/2011/05/001751

Lead Sponsor: Intas Pharmaceuticals limited

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 Moreover, this is also in agreement with the current draft guidance on Capecitabine by OGD, USFDA.xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /

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 marketedcapecitabineTablets 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

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 44

Inclusion Criteria

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.

Exclusion Criteria

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.

Study & Design

Study Type: BA/BE

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 Measures

Name	Time	Method
To monitor the safety of the patients, who are exposed to the Investigational Medicinal Product	NIL

Trial Locations

Locations (8): Bharatb Cancer Hospital & Research Institute
🇮🇳
Surat, GUJARAT, India
Central India Cancer Research Institute
🇮🇳
Nagpur, MAHARASHTRA, India
City Cancer Centre
🇮🇳
Visakhapatnam, ANDHRA PRADESH, India
Dr. Kamakshi Memorial Hospital Pvt Ltd
🇮🇳
Chennai, TAMIL NADU, India
Lions Cancer Detection Centre
🇮🇳
Surat, GUJARAT, India
Mahatma Gandhi Hospital & Research Institute
🇮🇳
Visakhapatnam, ANDHRA PRADESH, India
Meenakshi Mission Hospital & Research Centre
🇮🇳
Madurai, TAMIL NADU, India
Nandadeep Multispeciality Hospital
🇮🇳
Pune, MAHARASHTRA, India
Bharatb Cancer Hospital & Research Institute
🇮🇳Surat, GUJARAT, India
Dr Tanveer Maksud
Principal investigator
tanveermaksud@yahoo.com