CAP001

A pharmacokinetic study of adjuvant capecitabine in patients who have undergone proximal pancreatico-duodenectomy for resection of pancreatic adenocarcinoma

Research summary

To date, despite the increasing use of capecitabine in patients with pancreatic cancer, formal pharmacokinetic (PK) studies have not been undertaken in patients who have undergone proximal pancreatico-duodenectomy. Although the use of capecitabine is unlicensed in the treatment of patients with pancreatic cancer, it’s use in this clinical setting has been reviewed and locally approved both by the NHS Lothian Formulary Committee and by the Oncology Systemic Therapy Standards Group (OSTS) at Cambridge University Hospitals NHS Foundation Trust.

There have been studies in patients with oesophagogastric or gastric cancer that suggest gastrectomy did not adversely impair oral fluoropyrimidine absorption. Although, it is assumed that absorption of capecitabine occurs predominantly in the small intestine, the precise location is unknown and therefore, there is potential for proximal pancreatico-duodenectomy to impact on the absorbtion and therefore the PK of this drug.

Therefore this study aims to address the issue of whether proximal pancreatico-duodenectomy resection impacts on the availability of capecitabine for systemic absorption. If plasma concentrations of capecitabine were shown to be reduced in these patients, a formal dosefinding study might be required in this group of patients. This is a multicentre, non-randomised, pharmacokinetic study. Twelve patients with fully resected adenocarcinoma of the pancreas, who have undergone proximal pancreatico-duodenectomy will be entered into this study. Patients failing to complete PK sampling during Cycle 1 will be replaced.

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Main inclusion criteria

  • Complete macroscopic resection for pathologically proven ductal adenocarcinoma (or poorly differentiated / undifferentiated carcinoma) of the pancreas (R0 or R1 resection).

  • Surgery must have included a proximal pancreatico-duodenectomy.

  • Histological confirmation of the primary diagnosis and examination of all resection margins.

  • At least 4 weeks since surgery, fully recovered from the operation and all surgical wounds fully healed.

  • Age ≥ 18 years.

  • World Health Organisation (WHO) performance status of < 2.

  • Haematological and biochemical indices (these measurements must be performed within one week prior to the patient being registered on the study):

    • Haemoglobin (Hb) ≥9.0 g/dL (Patients may be transfused to this level, however, Hb must be above 9.0 g/dL before registration);

    • Neutrophils ≥1.5 x 109/L;
      - Platelets (Plts) ≥100 x 109/L;
      - Serum bilirubin <1.5 x ULN;
      - Alanine amino-transferase (ALT) and / or aspartate amino-transferase (AST) <2.0 x ULN. (If both are measured, both must be <2.0 x ULN);

    • Calculated creatinine clearance ≥50 mL/min (uncorrected value) or isotope clearance measurement ≥50 mL/min.

  • Female patients of child-bearing potential must have a negative serum or urine pregnancy test within two weeks 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.

Main exclusion criteria

  • Patients with pancreatic lymphoma or other histological diagnosis.

  • Macroscopically remaining tumour (R2 resection).

  • Evidence of malignant ascites, peritoneal or liver metastasis, or 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

  • Concurrent mechanical or malabsorptive disorders precluding affective oral administration of the drug (excluding malabsorption related directly to proximal pancreatic-duodenectomy).

  • Previous serious toxicity to fluoropyrimidines.

  • 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.

Funders and sponsors

Chief investigator

Prof Duncan Jodrell

Contact details

Cancer Theme Email: [email protected]