Pharmacokinetic Study of Adjuvant Capecitabine After Resection of Pancreatic Adenocarcinoma
Primary Purpose
Pancreatic Adenocarcinoma
Status
Completed
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
capecitabine
Sponsored by
About this trial
This is an interventional basic science trial for Pancreatic Adenocarcinoma focused on measuring capecitabine, Post whipples, pancreatico-duodenectomy, pancreatic adenocarcinoma, pharmacokinetic
Eligibility 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
Sites / Locations
- Cambridge University Hospitals NHS Foundation Trust, University of Cambridge Oncology Centre
- Edinburgh Cancer Centre, Western General Hospital
Outcomes
Primary Outcome Measures
To measure plasma levels of Capecitabine and its metabolites (DFCR, DFUR and 5-FU)
Secondary Outcome Measures
To evaluate adverse effects after every course of chemotherapy according to NCI-CTCAE V3.
To identify any dose limiting toxicities of Capecitabine
Full Information
NCT ID
NCT00854477
First Posted
February 27, 2009
Last Updated
February 15, 2013
Sponsor
Cambridge University Hospitals NHS Foundation Trust
1. Study Identification
Unique Protocol Identification Number
NCT00854477
Brief Title
Pharmacokinetic Study of Adjuvant Capecitabine After Resection of Pancreatic Adenocarcinoma
Official Title
A Pharmacokinetic Study of Adjuvant Capecitabine in Patients Who Have Undergone Proximal Pancreatico-duodenectomy for Resection of Pancreatic Adenocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2013
Overall Recruitment Status
Completed
Study Start Date
November 2009 (undefined)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
August 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Cambridge University Hospitals NHS Foundation Trust
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the pharmacokinetics (PK) of adjuvant capecitabine in patients who have undergone proximal pancreatico-duodenectomy.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Adenocarcinoma
Keywords
capecitabine, Post whipples, pancreatico-duodenectomy, pancreatic adenocarcinoma, pharmacokinetic
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
capecitabine
Other Intervention Name(s)
Xeloda
Intervention Description
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
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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).
Title
To identify any dose limiting toxicities of Capecitabine
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Duncan Jodrell, DM MSc FRCP
Organizational Affiliation
Cambridge University Hospitals, NHS Foundation Trust, University of Cambridge
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cambridge University Hospitals NHS Foundation Trust, University of Cambridge Oncology Centre
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
Edinburgh Cancer Centre, Western General Hospital
City
Edinburgh
Country
United Kingdom
12. IPD Sharing Statement
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Pharmacokinetic Study of Adjuvant Capecitabine After Resection of Pancreatic Adenocarcinoma
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