Pharmacokinetic Study of Capecitabine After Total Gastrectomy for Stomach Adenocarcinoma

This study is currently recruiting participants.
Verified February 2013 by Cambridge University Hospitals NHS Foundation Trust
Sponsor:
Information provided by (Responsible Party):
Duncan Jodrell, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00871273
First received: March 27, 2009
Last updated: February 15, 2013
Last verified: February 2013
  Purpose

The purpose of this study is to evaluate the pharmacokinetics (PK) of capecitabine in patients who have undergone a total gastrectomy.


Condition Intervention Phase
Adenocarcinoma of the Stomach
Drug: capecitabine
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Pharmacokinetic Study of Capecitabine in Patients Undergoing Peri-operative Chemotherapy and a Total Gastrectomy for Adenocarcinoma of the Stomach

Resource links provided by NLM:


Further study details as provided by Cambridge University Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • To establish the pharmacokinetics (PK) of capecitabine in patients who have undergone a total gastrectomy. [ Time Frame: Samples collected predose and 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, and 24 hours on day 1 of cycles 1 and 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To compare the pharmacokinetic profile of capecitabine administered to patients with gastric cancer pre- and post-gastrectomy and to compare this to historical data of capecitabine PK values in patients with other cancer types. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • To ensure equivalent capecitabine exposure when compared to PK data from the same patients prior to gastrectomy. [ Time Frame: 1 Year ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: November 2009
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: capecitabine
    film-coated tablet 1250 mg/m2 twice daily 14 days for 14 days. Number of cycles: 3 cycles pre-operatively and 3 cycles post-operatively unless there is evidence of disease progression on chemotherapy
    Other Name: Xeloda
Detailed Description:

Primary Objective:

  • To establish the pharmacokinetics (PK) of capecitabine in patients who have undergone a total gastrectomy

Secondary Objectives:

  • To compare the pharmacokinetic profile of capecitabine administered to patients with gastric cancer pre- and post-gastrectomy and to compare this to historical data of capecitabine PK values in patients with other cancer types.
  • To ensure equivalent capecitabine exposure when compared to PK data from the same patients prior to gastrectomy.

This is a clinical trial to evaluate the pharmacokinetics (PK) of capecitabine in patients who have undergone a total gastrectomy. The study also aims to establish the toxicity profile of capecitabine in these patients, to identify any dose limiting toxicities (DLT), and to ensure equivalent capecitabine exposure when compared to PK data from the same patients prior to gastrectomy. Screening tests will consist of demographic details, complete medical history, physical exam, vital signs, tumour serum markers, haematology and biochemistry tests. There will also be an ECG, chest X-Ray or CT thorax, CT abdomen and a serum or urine pregnancy test (for women of childbearing potential). Haematology and Biochemistry will be repeated prior to each study drug administration. All patients will receive 6 cycles of oral capecitabine chemotherapy at a dose of 625 mg/m2, administered twice daily at 12 hourly intervals for 21 consecutive days. Total proposed duration of therapy is 3 cycles pre-operatively and 3 cycles post-operatively. Capecitabine and its metabolites (DFCR, DFUR and 5-FU) plasma levels will be measured during the 1st and 4th cycles in all patients. Treatment should continue for 6 cycles unless there is evidence of disease progression, or unacceptable toxicity.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically confirmed gastric carcinoma suitable for potentially curative resection.
  • Surgery must be planned to involve a total gastrectomy.
  • No concurrent mechanical or malabsorptive disorders precluding affective oral administration of the drug (excluding early satiety related to the presence of the malignancy).
  • Age ≥ 18 years.
  • World Health Organisation (WHO) performance status of ≤ 2 (Appendix 1).
  • Haematological and biochemical indices (These measurements must be performed within one week prior to the patient going on study.)
  • Haemoglobin (Hb) ≥ 9.0 g/dl
  • Neutrophils ≥ 1.5 x 109/L
  • Platelets (Plts) ≥ 100 x 109/L
  • Serum bilirubin ≤ 1.5 x upper normal limit
  • Alanine amino-transferase (ALT) and / or aspartate amino-transferase (AST) ≤ 2.0 x upper limit of normal (ULN). (If both are measured, both must be ≤ 2.0 x ULN)
  • Calculated creatinine clearance ≥ 50 ml/min (uncorrected value) or isotope clearance measurement ≥ 50ml/min
  • Female patients of child-bearing potential must have a negative serum or urine pregnancy test prior to enrolment and agree to use appropriate medically approved contraception for four weeks prior to entering the trial, during the trial, and for six months afterwards.
  • Male patients must agree to use appropriate medically approved contraception during the trial and for six months afterwards.
  • Written, informed consent provided.
  • Ability of the patient to co-operate with treatment and follow up must be ensured.
  • Patients receiving oral anti-coagulation prior to entry into the study, must be converted to low molecular weight heparin in light of the interaction between capecitabine and warfarin.

Exclusion Criteria:

  • Patients with gastric lymphoma or other histological diagnosis
  • Any evidence of malignant ascites, peritoneal or liver metastasis, spread to other distant abdominal or extra-abdominal organs.
  • History of confirmed Ischaemic Heart Disease, concurrent congestive heart failure or prior history of class III / IV cardiac disease (Appendix 2 - New York Heart Association (NYHA) Scale)
  • Concurrent mechanical or malabsorptive disorders precluding effective oral administration of the drug
  • Use of other concomitant chemotherapy
  • Pregnancy or Lactation
  • Patients known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).
  • Patients who are high medical risks because of non-malignant systemic disease including active uncontrolled infection.
  • Any other serious medical or psychological condition precluding adjuvant treatment
  • Patients with any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00871273

Contacts
Contact: Duncan Jodrell, DM MSc FRCP 01223 769480 duncan.jodrell@cruk.cam.ac.uk

Locations
United Kingdom
Cambridge University Hospitals NHS Foundation Trust, University of Cambridge Oncology Centre Recruiting
Cambridge, United Kingdom
Contact: Duncan Jodrell, DM MSc FRCP       duncan.jodrell@cruk.cam.ac.uk   
Edinburgh Cancer Centre, Western General Hospital Recruiting
Edinburgh, United Kingdom
Contact: Lucy Wall, MD       lucy.wall@luht.scot.nhs.uk   
Sponsors and Collaborators
Cambridge University Hospitals NHS Foundation Trust
Investigators
Principal Investigator: Duncan Jodrell, DM MSc FRCP Cambridge University Hospitals, NHS Foundation Trust, University of Cambridge
  More Information

No publications provided

Responsible Party: Duncan Jodrell, Professor Duncan Jodrell, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT00871273     History of Changes
Other Study ID Numbers: CAP002
Study First Received: March 27, 2009
Last Updated: February 15, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Cambridge University Hospitals NHS Foundation Trust:
capecitabine
total gastrectomy
pharmacokinetic

Additional relevant MeSH terms:
Adenocarcinoma
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Capecitabine
Fluorouracil
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014