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

• Status: Completed
• Trial end date: 2012-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objective

1. To develop a pharmacokinetic-pharmacodynamic (PD) model for optimisation of docetaxel dosing

Secondary Objectives

1. To establish an exposure-toxicity (neutropenia) relationship for docetaxel

2. To determine the exposure breakpoint for docetaxel toxicity based on a neutropenia PD model

3. To identify demographic, pathophysiological and/or phenotypic covariates predicting docetaxel clearance

4. To prospectively validate this PK-PD model for optimisation of docetaxel dosage and determination PK variability and toxicity

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National University Hospital, Singapore
• Treatments: Docetaxel

Criteria

Inclusion Criteria:

1. Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which docetaxel is indicated.

2. Patients must have measurable or evaluable disease.

3. 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.

4. Patients must have ECOG performance status < 2 (Karnofsky >60%, see Appendix B).

5. Patients must have a life expectancy of greater than 3 months.

6. 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

7. 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.

8. 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.

9. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. 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.

2. Patients may not be receiving any other investigational agents.

3. Patients who have rapidly progressive intracranial or spinal metastatic disease (including patients who require corticosteroid for CNS disease).

4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel or other agents used in study.

5. Patients who have prior medications known to be metabolized by or induce/inhibit CYP3A4 within 1 week (see appendix C).

6. 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.

7. 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.