Clinical trial NCT01621425: Lean Body Mass as a Determinant of Docetaxel Pharmacokinetics and Toxicity
Official title: Lean Body Mass as a Determinant of Docetaxel Pharmacokinetics and Toxicity
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Metastatic Castration-resistant Prostate Carcinoma
Keywords: breast cancer
prostate carcinoma
docetaxel
lean body mass
Body Surface Area
body weight
dexascan
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2012-06-18
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 20 female subjects who are diagnosed with breast and 20 male subjects with metas-tatic castration-resistant prostate carcinoma and will receive docetaxel treatment according to standard hospital protocol (TAC or PRODOC regimens)

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: anthropometric parameters related to exposure
timeFrame: within one week prior to first docetaxel dose
Secondary outcomes:
measure: relation between docetaxel toxicity and dose/LBM
timeFrame: 1 cycle (21 days)
measure: determine the best method to measure lean body mass
timeFrame: within one week prior to first docetaxel dose
Other outcomes:
Locations:
city: Deventer
country: Netherlands
facility: Deventer Hospital
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
Study officials:
affiliation: Deventer Ziekenhuis
name: Rien Hoge, PharmD
role: PRINCIPAL_INVESTIGATOR
affiliation: Deventer Ziekenhuis
name: Frank Jansman, PharmD, PhD
role: STUDY_CHAIR
References: