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Association of Capecitabine Pharmacokinetics and Toxicity With Aging

7 maart 2018 bijgewerkt door: Newcastle-upon-Tyne Hospitals NHS Trust

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

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.

Studie Overzicht

Toestand

Onbekend

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Verwacht)

100

Fase

  • Fase 4

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

      -

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Fundamentele wetenschap
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Capecitabine
Geneesmiddel: Capecitabine
Andere namen:
  • Xeloda

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Area under the curve (AUC) of capecitabine and metabolites
Tijdsspanne: 0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose
Measurement of AUC of capecitabine and its metabolites 5'deoxy-5-fluorocytidine (5'DFCR), 5'deoxy-5-fluorouridine (5'DFUR), and 5-fluorouracil.
0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Toxicities and grades as scaled by Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.03
Tijdsspanne: Six months
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.
Six months
Progression free survival as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
Tijdsspanne: From time of enrollment until first documented progression
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)'
From time of enrollment until first documented progression
Response as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1
Tijdsspanne: From time of enrollment to first documented response

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.'
From time of enrollment to first documented response
Grip strength measured in kg
Tijdsspanne: During 6-hour pharmacokinetic study session
Grip strength measured in kg by the grip strength test (using the Takei handheld dynamometer)
During 6-hour pharmacokinetic study session
Frailty as measured by the Edmonton Frail Scale
Tijdsspanne: During 6-hour pharmacokinetic study session
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.
During 6-hour pharmacokinetic study session
Nutritional status as measured by the Mini Nutritional Assessment questionnaire
Tijdsspanne: During 6-hour pharmacokinetic study session

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.
During 6-hour pharmacokinetic study session
Quality of life as assessed by the European Organization for Research and Treatment of Cancer quality of life (EORTC-QLQ-C30 version 3) questionnaire
Tijdsspanne: During 6-hour pharmacokinetic study session
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'.
During 6-hour pharmacokinetic study session
Plasma cytidine deaminase activity (measured in units/mg protein by spectrophotometric assay)
Tijdsspanne: 0 hours post dose (pre-dose)
Plasma cytidine deaminase activity (measured in units/mg protein by spectrophotometric assay).
0 hours post dose (pre-dose)
Maximum plasma concentration (Cmax) of capecitabine and metabolites
Tijdsspanne: 0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose
Cmax of capecitabine and its metabolites 5'deoxy-5-fluorocytidine (5'DFCR), 5'deoxy-5-fluorouridine (5'DFUR), and 5-fluorouracil.
0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose
Time of maximum plasma concentration (Tmax) of capecitabine and metabolites
Tijdsspanne: 0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose
Cmax of capecitabine and its metabolites 5'deoxy-5-fluorocytidine (5'DFCR), 5'deoxy-5-fluorouridine (5'DFUR), and 5-fluorouracil.
0 (pre-dose), 0.5, 1, 2, 4, and 6 hours post dose

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Newcastle-upon-Tyne Hospitals NHS Trust

Medewerkers

University of Newcastle Upon-Tyne

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 mei 2016

Primaire voltooiing (Verwacht)

1 mei 2018

Studie voltooiing (Verwacht)

1 november 2019

Studieregistratiedata

Eerst ingediend

7 augustus 2015

Eerst ingediend dat voldeed aan de QC-criteria

7 maart 2018

Eerst geplaatst (Werkelijk)

14 maart 2018

Updates van studierecords

Laatste update geplaatst (Werkelijk)

14 maart 2018

Laatste update ingediend die voldeed aan QC-criteria

7 maart 2018

Laatst geverifieerd

1 maart 2018

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • SBRU201501

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