A Pharmacokinetic Study of Adjuvant Capecitabine in Patients Who Have Undergone Proximal Pancreatico-duodenectomy for Resection of Pancreatic Adenocarcinoma
18 Years
N/A
Both
Pancreatic Adenocarcinoma
Trial Information
A Pharmacokinetic Study of Adjuvant Capecitabine in Patients Who Have Undergone Proximal Pancreatico-duodenectomy for Resection of Pancreatic Adenocarcinoma
Primary Objective:
- To establish the pharmacokinetics (PK) of capecitabine in patients who have undergone
proximal pancreatico-duodenectomy.
Secondary objectives:
- To establish the toxicity profile of capecitabine in these patients and to identify any
dose limiting toxicities (DLT).
- To ensure equivalent capecitabine exposure when compared to previous studies using
patients who have not undergone such surgery.
This is a clinical trial to evaluate the pharmacokinetics (PK) of adjuvant capecitabine in
patients who have undergone proximal pancreatico-duodenectomy. 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
previous studies using patients who have not undergone such surgery. 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, faecal
elastase measurement and a serum or urine pregnancy test (for women of childbearing
potential). Haematology and Biochemistry (including CA19.9) will be repeated prior to each
study drug administration. All patients will receive 8 cycles of oral capecitabine
chemotherapy at a dose of 1250 mg/m2, administered twice daily at 12 hourly intervals for 14
consecutive days out of a 21 day cycle. Total proposed duration of therapy is 24 weeks,
assuming patients commence all cycles without delay. Capecitabine and its metabolites
(DFCR, DFUR and 5-FU) plasma levels will be measured during the 1st and 3rd cycles in all
patients. Treatment should continue for 8 cycles unless there is evidence of disease
progression, or unacceptable toxicity.
Inclusion Criteria:
- Surgery included proximal pancreatico-duodenectomy
- Complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1
resection)
- Histological confirmation of the primary diagnosis and examination of all resection
margins
- At least 4 weeks since surgery, fully recovered from the operation and fit to take
part in the trial
- Age ≥ 18 years
- World Health Organisation (WHO) performance status of ≤ 2 (Appendix 1)
- 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)
- 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 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 and
documented.
Exclusion Criteria:
- Pregnancy or Lactation
- Evidence of malignant ascites, peritoneal or liver metastasis, spread to other
distant abdominal or extra-abdominal organs.
- Concurrent mechanical or malabsorptive disorders precluding affective oral
administration of the drug (excluding malabsorption related directly to proximal
pancreatic-duodenectomy)
- Patients with pancreatic lymphoma or other histological diagnosis
- Macroscopically remaining tumour (R2 resection)
- Patients who are high medical risks because of non-malignant systemic disease
including active uncontrolled infection.
- Patients with any other condition which in the Investigator's opinion would not make
the patient a good candidate for the clinical trial.
- Patients known to be serologically positive for Hepatitis B, Hepatitis C or Human
Immunodeficiency Virus (HIV).
- History of confirmed Ischaemic Heart Disease, concurrent congestive heart failure or
prior history of class III/ IV cardiac disease (New York Heart Association [NYHA] -
refer to Appendix 5)
- Any serious medical or psychological condition precluding adjuvant treatment
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 measure plasma levels of Capecitabine and its metabolites (DFCR, DFUR and 5-FU)
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 3
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:
CAP001
NCT ID:
NCT00854477
Start Date:
November 2009
Completion Date:
August 2012
Related Keywords:
- Pancreatic Adenocarcinoma
- capecitabine
- Post whipples
- pancreatico-duodenectomy
- pancreatic adenocarcinoma
- pharmacokinetic
- Adenocarcinoma
- Adenocarcinoma, Mucinous
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