Pharmacokinetic Study of Adjuvant Capecitabine After Resection of Pancreatic Adenocarcinoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Duncan Jodrell, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00854477
First received: February 27, 2009
Last updated: February 15, 2013
Last verified: February 2013
  Purpose

The purpose of this study is to evaluate the pharmacokinetics (PK) of adjuvant capecitabine in patients who have undergone proximal pancreatico-duodenectomy.


Condition Intervention Phase
Pancreatic Adenocarcinoma
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 Adjuvant Capecitabine in Patients Who Have Undergone Proximal Pancreatico-duodenectomy for Resection of Pancreatic Adenocarcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • To measure plasma levels of Capecitabine and its metabolites (DFCR, DFUR and 5-FU) [ 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate adverse effects after every course of chemotherapy according to NCI-CTCAE V3. [ Time Frame: 1 year (from patient registration until 28 days after last study drug administration). ] [ Designated as safety issue: No ]
  • To identify any dose limiting toxicities of Capecitabine [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Enrollment: 13
Study Start Date: November 2009
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: capecitabine
    film-coated tablet 1250 mg/m2 twice daily for 14 days every 3 weeks. Number of cycles: 8 cycles unless there is evidence of disease progression, or unacceptable toxicity
    Other Name: Xeloda
Detailed Description:

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00854477

Locations
United Kingdom
Cambridge University Hospitals NHS Foundation Trust, University of Cambridge Oncology Centre
Cambridge, United Kingdom, CB2 0QQ
Edinburgh Cancer Centre, Western General Hospital
Edinburgh, United Kingdom
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: NCT00854477     History of Changes
Other Study ID Numbers: CAP001, PDDG/CAP001
Study First Received: February 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
Post whipples
pancreatico-duodenectomy
pancreatic adenocarcinoma
pharmacokinetic

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
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 July 24, 2014