Lean Body Mass as a Determinant of Docetaxel Pharmacokinetics and Toxicity

Breast Cancer Clinical Trial

— LEANDOC  

Official title:

Lean Body Mass as a Determinant of Docetaxel Pharmacokinetics and Toxicity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01621425
• Other study ID #: UMCN-AKF 11.01
• Status: Completed
• Phase: N/A
• First received: May 25, 2012
• Last updated: August 12, 2015
• Start date: June 2012
• Est. completion date: May 2015

Study information

• Verified date: August 2015
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Observational Model: Case-Only, Time Perspective: Prospective

Related Conditions & MeSH terms

• Breast Cancer
• Metastatic Castration-resistant Prostate Carcinoma
• Prostatic Neoplasms

Intervention

Other:
• Lean body mass
Lean Body mass (DEXA scan and Bioelectrical Impedance Assessments) within one week prior to the first docetaxel dose
• Total body weight
Total Body weight (TBW) (scale) within one week prior to the first docetaxel dose
• bloodsampling
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

Locations

Country	Name	City	State
Netherlands	Deventer Hospital	Deventer
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	anthropometric parameters related to exposure	To determine which anthropometric parameters, LBM, total body weight (TBW) or BSA correlates best to docetaxel exposure (AUC) for both males and females	within one week prior to first docetaxel dose	No
Secondary	relation between docetaxel toxicity and dose/LBM	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)	1 cycle (21 days)	Yes
Secondary	determine the best method to measure lean body mass	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.	within one week prior to first docetaxel dose	No