Lean Body Mass as a Determinant of Docetaxel Pharmacokinetics and Toxicity (LEANDOC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Radboud University
Sponsor:
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01621425
First received: May 25, 2012
Last updated: April 29, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention
Breast Cancer
Metastatic Castration-resistant Prostate Carcinoma
Other: Lean body mass
Other: Total body weight
Other: bloodsampling

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Lean Body Mass as a Determinant of Docetaxel Pharmacokinetics and Toxicity

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • anthropometric parameters related to exposure [ Time Frame: within one week prior to first docetaxel dose ] [ Designated as safety issue: No ]
    To determine which anthropometric parameters, LBM, total body weight (TBW) or BSA correlates best to docetaxel exposure (AUC) for both males and females


Secondary Outcome Measures:
  • relation between docetaxel toxicity and dose/LBM [ Time Frame: 1 cycle (21 days) ] [ Designated as safety issue: Yes ]
    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)

  • determine the best method to measure lean body mass [ Time Frame: within one week prior to first docetaxel dose ] [ Designated as safety issue: No ]
    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.


Biospecimen Retention:   Samples Without DNA

Blood samples for docetaxel concentration measurement (n=4)


Estimated Enrollment: 40
Study Start Date: June 2012
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
TAC regimen
Female subject diagnosed with breast carcinoma and will receive docetaxel treatment according to standard hospital protocol
Other: Lean body mass
Lean Body mass (DEXA scan and Bioelectrical Impedance Assessments) within one week prior to the first docetaxel dose
Other: Total body weight
Total Body weight (TBW) (scale) within one week prior to the first docetaxel dose
Other: 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
PRODOC regimen
male subject diagnosed with metastatic castration-resistant prostate carcinoma and will receive docetaxel treatment according to standard hospital protocol
Other: Lean body mass
Lean Body mass (DEXA scan and Bioelectrical Impedance Assessments) within one week prior to the first docetaxel dose
Other: Total body weight
Total Body weight (TBW) (scale) within one week prior to the first docetaxel dose
Other: 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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01621425

Contacts
Contact: David Burger, Prof +31 24 3616405 d.burger@akf.umcn.nl
Contact: Angela Colbers, MSc +31 24 3616405 a.colbers@akf.umcn.nl

Locations
Netherlands
Deventer Hospital Recruiting
Deventer, Netherlands
Contact: Rien Hoge, PharmD         
Principal Investigator: Frank Jansman, PharmD, PhD         
Radboud University Nijmegen Medical Centre Recruiting
Nijmegen, Netherlands
Contact: David Burger, Prof         
Principal Investigator: Carla v Herpen, MD         
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: Rien Hoge, PharmD Deventer Ziekenhuis
Study Chair: Frank Jansman, PharmD, PhD Deventer Ziekenhuis
  More Information

No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01621425     History of Changes
Other Study ID Numbers: UMCN-AKF 11.01
Study First Received: May 25, 2012
Last Updated: April 29, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
breast cancer
prostate carcinoma
docetaxel
lean body mass
Body Surface Area
body weight
dexascan

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Prostatic Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Prostatic Diseases
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014