Clinical trial NCT03465202: Association of Capecitabine Pharmacokinetics and Toxicity With Aging
Official title: A Prospective Evaluation of Capecitabine and Metabolite Pharmacokinetics in Elderly Breast and Colorectal Cancer Patients and Their Association With Toxicity and Molecular Markers of Enzyme Activity and Aging
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Breast Cancer
Colorectal Cancer
Keywords: Capecitabine
Pharmacokinetics
Ageing
Frailty
Breast cancer
Colorectal cancer
Lead sponsor: Newcastle-upon-Tyne Hospitals NHS Trust
Sponsor class: OTHER
Collaborators: name: University of Newcastle Upon-Tyne
First posted: 2018-03-14
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: This is a multi-centre prospective non-interventional study designed to evaluate the effects of patient age on the pharmacokinetics of capecitabine and its metabolites 5'DFCR, 5'DFUR, and 5-FU. In addition, the study will assess the correlation between the pharmacokinetic parameters calculated and cytidine deaminase, biomarkers of aging, clinical frailty, treatment outcome, and toxicity. To be enrolled, patients must have breast or colorectal cancer and be eligible to receive capecitabine monotherapy in accordance with its approved clinical usage in the UK. Treatment will be administered according to NICE guidelines as well as the clinical judgement of the prescribing physician. One hundred patients (50 breast cancer patients, 50 colorectal cancer patients) who are about to start treatment with capecitabine monotherapy will be recruited to the study and undergo study procedures within the first week of treatment.


Eligibility criteria: Inclusion Criteria:

* 1) Histologic or cytologic diagnosis of breast cancer or colorectal cancer. Patients should have disease that is suitable for capecitabine monotherapy as defined by the NICE Guidelines.

  2) Patients must be within the first week of their first cycle of capecitabine treatment.

  3) Estimated life expectancy of greater than 3 months. 4) Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. 5) Total serum bilirubin less than or equal to 25 micromol/L. 6) Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels less than 2.5 times the upper limit of the normal range.

  7) Serum albumin level greater than 32 g/L. 8) Creatinine clearance greater than or equal to 30 mL/minute. 9) Blood haemoglobin level of greater than 9 g/dL, with transfusion allowed. 10) Absolute neutrophil count greater than 2.5 x 109/L. 11) Platelet count greater than 100 x 109/L. 12) 18 years of age or older. 13) Written informed consent.

Exclusion Criteria:

1. Pregnancy or breast feeding.
2. Known HIV, Hepatitis B, or Hepatitis C infection.
3. Known Gilbert syndrome.
4. Uncontrolled diabetes (HbA1c greater than 7.5%).
5. Any condition or disease that might affect oral absorption of medications, including:

   1. Crohn's disease
   2. Ulcerative colitis
   3. Major gastric or small bowel resection

      -

Primary outcomes:
measure: Area under the curve (AUC) of capecitabine and metabolites
timeFrame: 0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose
Secondary outcomes:
measure: Toxicities and grades as scaled by Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.03
timeFrame: Six months
measure: Progression free survival as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
timeFrame: From time of enrollment until first documented progression
measure: Response as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
timeFrame: From time of enrollment to first documented response
measure: Grip strength measured in kg
timeFrame: During 6-hour pharmacokinetic study session
measure: Frailty as measured by the Edmonton Frail Scale
timeFrame: During 6-hour pharmacokinetic study session
measure: Nutritional status as measured by the Mini Nutritional Assessment questionnaire
timeFrame: During 6-hour pharmacokinetic study session
measure: Quality of life as assessed by the European Organization for Research and Treatment of Cancer quality of life (EORTC-QLQ-C30 version 3) questionnaire
timeFrame: During 6-hour pharmacokinetic study session
measure: Plasma cytidine deaminase activity (measured in units/mg protein by spectrophotometric assay)
timeFrame: 0 hours post dose (pre-dose)
measure: Maximum plasma concentration (Cmax) of capecitabine and metabolites
timeFrame: 0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose
measure: Time of maximum plasma concentration (Tmax) of capecitabine and metabolites
timeFrame: 0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose
Other outcomes:
Locations:
Study officials:
References: