Back to resultsAssociation of Capecitabine Pharmacokinetics and Toxicity With Aging
Primary Purpose
Breast Cancer, Colorectal Cancer
Status
Unknown status
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Capecitabine
Sponsored by
About this trial
This is an interventional basic science trial for Breast Cancer focused on measuring Capecitabine, Pharmacokinetics, Ageing, Frailty, Breast cancer, Colorectal cancer
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:
- Pregnancy or breast feeding.
- Known HIV, Hepatitis B, or Hepatitis C infection.
- Known Gilbert syndrome.
- Uncontrolled diabetes (HbA1c greater than 7.5%).
Any condition or disease that might affect oral absorption of medications, including:
- Crohn's disease
- Ulcerative colitis
Major gastric or small bowel resection
-
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Capecitabine
Arm Description
Outcomes
Primary Outcome Measures
Area under the curve (AUC) of capecitabine and metabolites
Measurement of AUC of capecitabine and its metabolites 5'deoxy-5-fluorocytidine (5'DFCR), 5'deoxy-5-fluorouridine (5'DFUR), and 5-fluorouracil.
Secondary Outcome Measures
Toxicities and grades as scaled by Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.03
Toxicity grade(s) as measured by CTCAE version 4.03 (published by the U.S. Department of Heath and Human Services 2009). General grading scheme is as follows: Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
Progression free survival as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
Progression free survival as measured by the RECIST criteria version 1.1 (Eisenhauer et al., 2009). The RECIST criteria define progression as 'at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression)'
Response as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
Complete or partial response as measured by the RECIST criteria version 1.1. (Eisenhauer et al., 2009) Complete response = 'Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Partial response = 'At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.'
Grip strength measured in kg
Grip strength measured in kg by the grip strength test (using the Takei handheld dynamometer)
Frailty as measured by the Edmonton Frail Scale
Frailty as measured by the Edmonton Frail Scale. A 17 point scale that measures 9 frailty domains. 0-5: not frail; 6-7: vulnerable; 8-9: mild frailty; 10-11: moderate frailty; 12-17: severe frailty.
Nutritional status as measured by the Mini Nutritional Assessment questionnaire
Nutritional status as measured by the Mini Nutritional Assessment questionnaire, a 30 point test on nutritional status. Scoring: 24 to 30 points: Normal nutritional status.
17 to 23.5 points: At risk of malnutrition. Less than 17 points: malnourished.
Quality of life as assessed by the European Organization for Research and Treatment of Cancer quality of life (EORTC-QLQ-C30 version 3) questionnaire
Quality of life as measured by the EORTC-QLQ-C30 version 3 questionnaire. This questionnaire assesses the quality of life of cancer patients in a series of 30 questions, with 28 of the questions on a scale of 1 to 4 where 1 is 'not at all' and 4 is 'very much'. Final two questions relate to overall quality of life and health on a scale of 1 to 7, where 1 is 'very poor' and 7 is 'excellent'.
Plasma cytidine deaminase activity (measured in units/mg protein by spectrophotometric assay)
Plasma cytidine deaminase activity (measured in units/mg protein by spectrophotometric assay).
Maximum plasma concentration (Cmax) of capecitabine and metabolites
Cmax of capecitabine and its metabolites 5'deoxy-5-fluorocytidine (5'DFCR), 5'deoxy-5-fluorouridine (5'DFUR), and 5-fluorouracil.
Time of maximum plasma concentration (Tmax) of capecitabine and metabolites
Cmax of capecitabine and its metabolites 5'deoxy-5-fluorocytidine (5'DFCR), 5'deoxy-5-fluorouridine (5'DFUR), and 5-fluorouracil.
Full Information
NCT ID
NCT03465202
First Posted
August 7, 2015
Last Updated
March 7, 2018
Sponsor
Newcastle-upon-Tyne Hospitals NHS Trust
Collaborators
University of Newcastle Upon-Tyne
1. Study Identification
Unique Protocol Identification Number
NCT03465202
Brief Title
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
2. Study Status
Record Verification Date
March 2018
Overall Recruitment Status
Unknown status
Study Start Date
May 2016 (undefined)
Primary Completion Date
May 2018 (Anticipated)
Study Completion Date
November 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Newcastle-upon-Tyne Hospitals NHS Trust
Collaborators
University of Newcastle Upon-Tyne
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Colorectal Cancer
Keywords
Capecitabine, Pharmacokinetics, Ageing, Frailty, Breast cancer, Colorectal cancer
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
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Capecitabine
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Primary Outcome Measure Information:
Title
Area under the curve (AUC) of capecitabine and metabolites
Description
Measurement of AUC of capecitabine and its metabolites 5'deoxy-5-fluorocytidine (5'DFCR), 5'deoxy-5-fluorouridine (5'DFUR), and 5-fluorouracil.
Time Frame
0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose
Secondary Outcome Measure Information:
Title
Toxicities and grades as scaled by Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.03
Description
Toxicity grade(s) as measured by CTCAE version 4.03 (published by the U.S. Department of Heath and Human Services 2009). General grading scheme is as follows: Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
Time Frame
Six months
Title
Progression free survival as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
Description
Progression free survival as measured by the RECIST criteria version 1.1 (Eisenhauer et al., 2009). The RECIST criteria define progression as 'at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: the appearance of one or more new lesions is also considered progression)'
Time Frame
From time of enrollment until first documented progression
Title
Response as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
Description
Complete or partial response as measured by the RECIST criteria version 1.1. (Eisenhauer et al., 2009) Complete response = 'Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
Partial response = 'At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.'
Time Frame
From time of enrollment to first documented response
Title
Grip strength measured in kg
Description
Grip strength measured in kg by the grip strength test (using the Takei handheld dynamometer)
Time Frame
During 6-hour pharmacokinetic study session
Title
Frailty as measured by the Edmonton Frail Scale
Description
Frailty as measured by the Edmonton Frail Scale. A 17 point scale that measures 9 frailty domains. 0-5: not frail; 6-7: vulnerable; 8-9: mild frailty; 10-11: moderate frailty; 12-17: severe frailty.
Time Frame
During 6-hour pharmacokinetic study session
Title
Nutritional status as measured by the Mini Nutritional Assessment questionnaire
Description
Nutritional status as measured by the Mini Nutritional Assessment questionnaire, a 30 point test on nutritional status. Scoring: 24 to 30 points: Normal nutritional status.
17 to 23.5 points: At risk of malnutrition. Less than 17 points: malnourished.
Time Frame
During 6-hour pharmacokinetic study session
Title
Quality of life as assessed by the European Organization for Research and Treatment of Cancer quality of life (EORTC-QLQ-C30 version 3) questionnaire
Description
Quality of life as measured by the EORTC-QLQ-C30 version 3 questionnaire. This questionnaire assesses the quality of life of cancer patients in a series of 30 questions, with 28 of the questions on a scale of 1 to 4 where 1 is 'not at all' and 4 is 'very much'. Final two questions relate to overall quality of life and health on a scale of 1 to 7, where 1 is 'very poor' and 7 is 'excellent'.
Time Frame
During 6-hour pharmacokinetic study session
Title
Plasma cytidine deaminase activity (measured in units/mg protein by spectrophotometric assay)
Description
Plasma cytidine deaminase activity (measured in units/mg protein by spectrophotometric assay).
Time Frame
0 hours post dose (pre-dose)
Title
Maximum plasma concentration (Cmax) of capecitabine and metabolites
Description
Cmax of capecitabine and its metabolites 5'deoxy-5-fluorocytidine (5'DFCR), 5'deoxy-5-fluorouridine (5'DFUR), and 5-fluorouracil.
Time Frame
0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose
Title
Time of maximum plasma concentration (Tmax) of capecitabine and metabolites
Description
Cmax of capecitabine and its metabolites 5'deoxy-5-fluorocytidine (5'DFCR), 5'deoxy-5-fluorouridine (5'DFUR), and 5-fluorouracil.
Time Frame
0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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:
Pregnancy or breast feeding.
Known HIV, Hepatitis B, or Hepatitis C infection.
Known Gilbert syndrome.
Uncontrolled diabetes (HbA1c greater than 7.5%).
Any condition or disease that might affect oral absorption of medications, including:
Crohn's disease
Ulcerative colitis
Major gastric or small bowel resection
-
12. IPD Sharing Statement
Learn more about this trial
Association of Capecitabine Pharmacokinetics and Toxicity With Aging
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