Pharmacokinetic Study of Adjuvant Capecitabine After Resection of Pancreatic Adenocarcinoma - Full Text View

Sponsored by:	Cambridge University Hospitals NHS Foundation Trust
Information provided by:	Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:	NCT00854477

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 IV

Drug Information available for: Capecitabine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Basic Science, Open Label, Single Group Assignment, Pharmacokinetics Study
Official Title:	A Pharmacokinetic Study of Adjuvant Capecitabine in Patients Who Have Undergone Proximal Pancreatico-Duodenectomy for Resection of Pancreatic Adenocarcinoma

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 ]

Estimated Enrollment:	12
Study Start Date:	May 2009
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Intervention Details:

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

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

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

Contacts

Contact: Duncan Jodrell, DM MSc FRCP

01223769480

duncan.jodrell@cancer.org.uk

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, EH4 2XU

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:	University of Cambridge ( Professor Duncan Jodrell )
Study ID Numbers:	CAP001, PDDG/CAP001
Study First Received:	February 27, 2009
Last Updated:	March 27, 2009
ClinicalTrials.gov Identifier:	NCT00854477 History of Changes
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

Study placed in the following topic categories:

Antimetabolites
Capecitabine
Adjuvants, Immunologic

Adenocarcinoma
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Antimetabolites
Capecitabine
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action

Antineoplastic Agents
Therapeutic Uses
Adenocarcinoma
Pharmacologic Actions
Neoplasms, Glandular and Epithelial
Carcinoma

ClinicalTrials.gov processed this record on May 06, 2009