Target Dosing of Docetaxel Through Pharmacokinetic/Pharmacodynamic Optimisation of the First Chemotherapeutic Cycle

NCT00703378 | Completed Phase 1

• 2 other identifiers: PK01/06/052005/00082
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective 1\. To develop a pharmacokinetic-pharmacodynamic (PD) model for optimisation of docetaxel dosing Secondary Objectives

1. 1.To establish an exposure-toxicity (neutropenia) relationship for docetaxel
2. 2.To determine the exposure breakpoint for docetaxel toxicity based on a neutropenia PD model
3. 3.To identify demographic, pathophysiological and/or phenotypic covariates predicting docetaxel clearance
4. 4.To prospectively validate this PK-PD model for optimisation of docetaxel dosage and determination PK variability and toxicity

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (1)

• change in neutrophil counts and docetaxel AUC

  . Based on maximal acceptable toxicity, expressed as the reduction in neutrophil count, the corresponding breakpoint for AUC will be identified as the PK target. Both linear regression and nonlinear mixed effects modeling will be employed to establish a relationship between docetaxel CL and demographic, phenotypic and pathophysiological factors.

  3 weeks

Secondary Outcomes (1)

• Pharmacokinetic sampling of docetaxel serum concentrations

  7 weeks

Study Arms (3)

Group 1

EXPERIMENTAL

Group 1: normal liver function

Drug: Docetaxel (Taxotere®)

Group 2

EXPERIMENTAL

Group 2: AST and/or ALT up to 1-5 x upper limit of normal; SAP 1- 5x upper limit of normal, total bilirubin within normal limits

Drug: Docetaxel (Taxotere®)

Group 3

EXPERIMENTAL

Group 3: Any SAP and AST/ALT \>5-10 x upper limit of normal and/or total bilirubin 1-1.5 x upper limit of normal

Drug: Docetaxel (Taxotere®)

Interventions

Docetaxel (Taxotere®) DRUG

Phase 1 Cycle 1 and 2 Patients in group 1 receive 40mg/m2/week of docetaxel in a 1-hour infusion. Patients in group 2 receive 30mg/m2/week of docetaxel in a 1-hour infusion. Patients in group 3 receive 20mg/m2/week of docetaxel in a 1-hour infusion.

Also known as: Taxotere®

Group 1; Group 2; Group 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which docetaxel is indicated.
• Patients must have measurable or evaluable disease.
• With the exception of alopecia, fatigue, nausea and asthenia, patients must have resolution of all acute toxic effects of any prior surgery' radiotherapy or chemotherapy to National Cancer Institute (NCI) Common Toxicity Criteria version 3.0 (see Appendix A) grade \< 1.
• Patients must have ECOG performance status \< 2 (Karnofsky \>60%, see Appendix B).
• Patients must have a life expectancy of greater than 3 months.
• Patients must have normal renal and marrow function as defined below:
• leukocytes ≥3,000/μl
• absolute neutrophil count ≥1,500/μl
• platelets ≥100,000/μl
• haemoglobin ≥7g/dL
• creatinine ≤1.5 X institutional upper limit of normal
• Patients with abnormal liver function tests (AST/ALT ≤ 10 x institutional upper limits of normal; SAP \< 5x ULN; total bilirubin ≤ 1.5x ULN) will be eligible for enrolment.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Females with childbearing potential must have a negative serum pregnancy test within 7days prior to study enrollment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients may not be receiving any other investigational agents.
• Patients who have rapidly progressive intracranial or spinal metastatic disease (including patients who require corticosteroid for CNS disease).
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel or other agents used in study.
• Patients who have prior medications known to be metabolized by or induce/inhibit CYP3A4 within 1 week (see appendix C).
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because docetaxel is embryotoxic/fetotoxic with the potential for abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with docetaxel, breastfeeding should be discontinued if the mother is treated with docetaxel. These potential risks may also apply to other agents used in this study.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore

Location

Related Publications (3)

• Goh BC, Lehnert M, Lim HL, Ng AW, Chan CC, Kong HL, Lee SC, Wee J, Chua ET, Wong JE. Phase II trial of docetaxel in Asian patients with inoperable stage III non-small cell lung cancer. Acta Oncol. 2000;39(2):225-9. doi: 10.1080/028418600430824.

  PMID: 10859016 BACKGROUND

• Goh BC, Lee SC, Wang LZ, Fan L, Guo JY, Lamba J, Schuetz E, Lim R, Lim HL, Ong AB, Lee HS. Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies. J Clin Oncol. 2002 Sep 1;20(17):3683-90. doi: 10.1200/JCO.2002.01.025.

  PMID: 12202670 BACKGROUND

• Syn NL, Wang L, Wong AL, Soe MY, Chuah B, Chan D, Tan SH, Soo RA, Lee SC, Goh BC, Yong WP. Dose modifications in Asian cancer patients with hepatic dysfunction receiving weekly docetaxel: A prospective pharmacokinetic and safety study. Cancer Sci. 2016 Feb;107(2):173-80. doi: 10.1111/cas.12856. Epub 2016 Feb 8.

  PMID: 26663719 DERIVED

MeSH Terms

Interventions

Docetaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Boon Cher Goh, MBBS, MRCP

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Goh Boon Cher

Study Record Dates

• First Submitted: June 20, 2008
• First Posted: June 23, 2008
• Study Start: May 1, 2006
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2012
• Last Updated: March 28, 2012

Record last verified: 2012-03

Locations

SG (1)