CAP002

A pharmacokinetic study of capecitabine in patients undergoing peri-operative chemotherapy and a total gastrectomy for adenocarcinoma of the stomach

Research summary

This is a clinical trial to evaluate the pharmacokinetics (PK) of adjuvant capecitabine in patients who have undergone a total gastrectomy. The study will compare the pharmacokinetic profile of capecitabine administered to patients with gastric cancer pre- and post-gastrectomy (using patients as their own controls) and also compare the data accrued with historical data for capecitabine PK. The aim is to ensure equivalent capecitabine exposure following total gastrectomy.

Screening tests will consist of demographic details, complete medical history, physical exam, vital signs, haematology and biochemistry tests. ECG, tumour measurement (CT abdomen, Chest X-ray or CT Chest) and a serum or urine pregnancy test (for women of childbearing potential) will also be performed. Haematology and biochemistry will be repeated prior to each study drug administration.

All patients will receive ECX chemotherapy which includes epirubicin 50mg/m2 (iv bolus) on day 1, cisplatin 60mg/m2 (iv infusion) on day 1 and oral capecitabine chemotherapy at a dose of 625mg/m2 administered twice daily at 12 hourly intervals for 21 consecutive days out of a 21 day cycle.

The concentration of capecitabine and its metabolites (DFCR, DFUR, 5-FU and FBAL) in plasma will be measured during the 1st and 4th cycles in all patients, using an established analytical method. An optional pharmacogenetic sample will be collected. Treatment will continue for 3 cycles pre-operatively and 3 cycles post-operatively unless there is evidence of disease progression on chemotherapy, unacceptable toxicity or treatment is discontinued at the patient??s request. Following completion or discontinuation of chemotherapy, follow-up will continue to be undertaken by their specialist (oncological and surgical) teams.

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Main inclusion criteria

  1. Patients must have histologically confirmed gastric carcinoma suitable for potentially curative resection.

  2. Surgery must be planned to involve a total gastrectomy.

  3. No concurrent mechanical or malabsorptive disorders precluding affective oral administration of the drug (excluding early satiety related to the presence of the malignancy).

  4. Age ≥ 18 years.

  5. World Health Organisation (WHO) performance status of ≤ 2 (Appendix 1).

  6. Haematological and biochemical indices (These measurements must be performed within one week prior to the patient going on study.)

  7. Haemoglobin (Hb) ≥ 9.0 g/dl

  8. Neutrophils ≥ 1.5 x 109/L

  9. Platelets (Plts) ≥ 100 x 109/L

  10. Serum bilirubin ≤ 1.5 x upper normal limit

  11. 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)

  12. Calculated creatinine clearance ≥ 50 ml/min (uncorrected value) or isotope clearance measurement ≥ 50ml/min

  13. 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.

  14. Male patients must agree to use appropriate medically approved contraception during the trial and for six months afterwards.

  15. Written, informed consent provided.

  16. Ability of the patient to co-operate with treatment and follow up must be ensured.

  17. 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.

Main exclusion criteria

 

  1. Patients with gastric lymphoma or other histological diagnosis

  2. Any evidence of malignant ascites, peritoneal or liver metastasis, spread to other distant abdominal or extra-abdominal organs.

  3. 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)

  4. Concurrent mechanical or malabsorptive disorders precluding effective oral administration of the drug

  5. Use of other concomitant chemotherapy

  6. Pregnancy or Lactation

  7. Patients known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV).

  8. Patients who are high medical risks because of non-malignant systemic disease including active uncontrolled infection.

  9. Any other serious medical or psychological condition precluding adjuvant treatment

  10. Patients with any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial.

Funders and sponsors

Chief investigator

Prof Duncan Jodrell

Contact details

Cancer Theme Email: [email protected]