Lean Body Mass as a Determinant of Docetaxel Pharmacokinetics and Toxicity (LEANDOC)
Docetaxel is used as a first line anti-cancer drug in the treatment of several cancers, mainly breast- and metastatic castration-resistant prostate carcinoma.
Anti-cancer drugs are being dosed based on patients estimated Body Surface Area in order to equalize total drug exposure. Nevertheless, docetaxel treatment is characterized by highly interindividual pharmacokinetic variation leading to toxicity and under-treatment.
The investigators will determine which anthropometric parameters, LBM, total body weight (TBW) or BSA correlate best to docetaxel exposure (AUC) for both males and females.
Study Overview
Status
Intervention / Treatment
Detailed Description
Docetaxel is used as a first line anti-cancer drug in the treatment of several cancers, mainly breast- and metastatic castration-resistant prostate carcinoma.
Anti-cancer drugs are being dosed based on patients estimated Body Surface Area in order to equalize total drug exposure. Nevertheless, docetaxel treatment is characterized by highly interindividual pharmacokinetic variation leading to toxicity and under-treatment.
For most anti-cancer drugs, including docetaxel, other anthropometric parameters, such as Lean Body Mass (LBM), have been suggested to be superior to Body Surface Are (BSA) as a determinant for dosing but this has not been implemented in clinical practice.
The investigators will determine which anthropometric parameters, LBM, total body weight (TBW) or BSA correlate best to docetaxel exposure (AUC) for both males and females.
The investigators will determine if occurrence of docetaxel toxicity can be related to dose/LBM.
The investigators will determine which methods to measure LBM: DEXA, Bioelectrical Impedance Assessments (BIA) or formula estimates are accurate enough for dosing calculations to be used for dosing docetaxel.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Deventer, Netherlands
- Deventer Hospital
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Nijmegen, Netherlands
- Radboud University Nijmegen Medical Centre
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Subject is at least 18
- Subject is able and willing to sign the Informed Consent Form prior to screening evaluations
- Female subject diagnosed with breast carcinoma and will receive docetaxel treatment according to standard hospital protocol (TAC regimen) or male subject diagnosed with metastatic castration-resistant prostate carcinoma and will receive docetaxel treatment according to standard hospital protocol (PRODOC regimen)
- Subject has a live expectancy of 12 weeks or greater
- Absolute neutrophile count (ANC) > 1.5 x 10E9/L
- Platelet count > 100 x 10E9/L
- Serum creatinine ≤ 2 x ULN
- Total bilirubin level < 1.5 x ULN
Exclusion Criteria:
- Docetaxel treatment within the last year
- Moderate or severe liver impairment; [ALAT and/or ASAT ≥ 1.5 ULN] and [AF ≥ 2.5 ULN]
- Current therapy with any drug, dietary supplements, or other compounds, or have been used in the last 2 weeks prior to the first docetaxel administration, known to inhibit or induce CYP3A4.
- Inability to understand the nature and extent of the study and the procedures required
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
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TAC regimen
Female subject diagnosed with breast carcinoma and will receive docetaxel treatment according to standard hospital protocol
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Lean Body mass (DEXA scan and Bioelectrical Impedance Assessments) within one week prior to the first docetaxel dose
Total Body weight (TBW) (scale) within one week prior to the first docetaxel dose
Blood samples will be taken during the first docetaxel administration of the first cycle, just before docetaxel infusion (t=0 min.),
30 min after start of infusion (t=30 min.),
just prior to end of infusion (t=55 min.)
and between 3 to 6 hours post start infusion following a limited sampling model
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PRODOC regimen
male subject diagnosed with metastatic castration-resistant prostate carcinoma and will receive docetaxel treatment according to standard hospital protocol
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Lean Body mass (DEXA scan and Bioelectrical Impedance Assessments) within one week prior to the first docetaxel dose
Total Body weight (TBW) (scale) within one week prior to the first docetaxel dose
Blood samples will be taken during the first docetaxel administration of the first cycle, just before docetaxel infusion (t=0 min.),
30 min after start of infusion (t=30 min.),
just prior to end of infusion (t=55 min.)
and between 3 to 6 hours post start infusion following a limited sampling model
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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anthropometric parameters related to exposure
Time Frame: within one week prior to first docetaxel dose
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To determine which anthropometric parameters, LBM, total body weight (TBW) or BSA correlates best to docetaxel exposure (AUC) for both males and females
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within one week prior to first docetaxel dose
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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relation between docetaxel toxicity and dose/LBM
Time Frame: 1 cycle (21 days)
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can docetaxel toxicity be related to dose/LBM?
docetaxel toxicity is defined as: number of rates of grade 3/4 toxicity, dose delay, dose reduction, treatment termination and combinations of all four as Dose-Limiting Toxicity (DLT)
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1 cycle (21 days)
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determine the best method to measure lean body mass
Time Frame: within one week prior to first docetaxel dose
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To determine which methods to measure LBM: Bioelectrical Impedance As-sessments (BIA) or formula estimates are accurate enough for dosing calculations to be used for dosing docetaxel.
These methods will be compared to the LBM derived from the DEXA scan as the general accepted, accurate and validated method for determining LBM.
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within one week prior to first docetaxel dose
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Collaborators and Investigators
Investigators
- Principal Investigator: Rien Hoge, PharmD, Deventer Ziekenhuis
- Study Chair: Frank Jansman, PharmD, PhD, Deventer Ziekenhuis
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- UMCN-AKF 11.01
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