A Pharmacokinetic Study of Capecitabine in Patients Undergoing Peri-operative Chemotherapy and a Total Gastrectomy for Adenocarcinoma of the Stomach
18 Years
N/A
Both
Adenocarcinoma of the Stomach
Trial Information
A Pharmacokinetic Study of Capecitabine in Patients Undergoing Peri-operative Chemotherapy and a Total Gastrectomy for Adenocarcinoma of the Stomach
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.
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.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
Outcome Measure:
To establish the pharmacokinetics (PK) of capecitabine in patients who have undergone a total gastrectomy.
Outcome 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
Safety Issue:
No
Principal Investigator
Duncan Jodrell, DM MSc FRCP
Investigator Role:
Principal Investigator
Investigator Affiliation:
Cambridge University Hospitals, NHS Foundation Trust, University of Cambridge
Authority:
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Study ID:
CAP002
NCT ID:
NCT00871273
Start Date:
November 2009
Completion Date:
Related Keywords:
- Adenocarcinoma of the Stomach
- capecitabine
- total gastrectomy
- pharmacokinetic
- Adenocarcinoma
- Adenocarcinoma, Mucinous
- Stomach Neoplasms
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