Effects Of GW572016 In Combination With Docetaxel (TAXOTERE)

Study Overview
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Brief Summary
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This is a safety and tolerability study of GW572016 given with docetaxel (TAXOTERE).

Official Title
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A Phase I, Open-Label Study of the Safety, Tolerability and Pharmacokinetics of GW572016 in Combination With Docetaxel (Taxotere)

Conditions
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Neoplasms, Breast

Intervention / Treatment
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* Drug: lapatinib
* Drug: docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced solid tumors. Able to swallow oral medication.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All treated subjects<br>All subjects received Lapatinib in Combination with Docetaxel (Taxotere) | Drug: lapatinib<br>* lapatinib<br>Drug: docetaxel<br>* docetaxel<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events (AEs) or serious AEs (SAEs) | An AE is any untoward medical occurrence in a subject or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require medical or surgical intervention will be categorized as SAE. | Up to 7 weeks in each cycle | 
| Number of subjects with abnormal change from Baseline in laboratory parameters | Blood sample will be collected to evaluate laboratory parameters. | Baseline and up to 7 weeks in each cycle | 
| Number of subjects with Optimally Tolerated regimen | Optimally Tolerated regimen is a dose regimen where 1 out of 6 subjects experiences a dose-limiting toxicity (DLT). | Up to 7 weeks in each cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma drug concentration curve (AUC) from 0 to infinity (AUC[0-inf]) of docetaxel alone (Pharmacokinetic [PK] cohort 1) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 1 and Sequence 2, Day 22: Prior to the docetaxel infusion, at 20 and 40 minutes after the start of the infusion, at 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after start of the infusion. | 
| AUC within the dosing interval (AUC[0-tau]) of GW572016 alone (PK cohort 2) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 1 and Sequence 2, Day 21: Prior to GW572016 dose and at 20 and 40 minutes; 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after the dose. | 
| AUC (0-tau) of GW572016 when given in combination with docetaxel (PK cohort 1) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 22 and Sequence 2, Day 1: Prior to the GW572016 oral dose and docetaxel infusion, at 20 and 40 minutes after the start of the infusion, at 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after the start of the docetaxel infusion. | 
| AUC (0-tau) of GW572016 when given in combination with docetaxel (PK cohort 2) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 23 and Sequence 2, Day 1: Prior to the GW572016 oral dose and docetaxel infusion, at 20 and 40 minutes after the start of the infusion, at 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after the start of the docetaxel infusion | 
| Maximum observed plasma drug concentration (Cmax) of docetaxel alone (PK cohort 1) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 1 and Sequence 2, Day 22: Prior to the docetaxel infusion, at 20 and 40 minutes after the start of the infusion, at 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after start of the infusion. | 
| Cmax of GW572016 alone (PK cohort 2) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 1 and Sequence 2, Day 21: Prior to GW572016 dose and at 20 and 40 minutes; 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after the dose. | 
| Cmax of GW572016 when given in combination with docetaxel (PK cohort 1) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 22 and Sequence 2, Day 1: Prior to the GW572016 oral dose and docetaxel infusion, at 20 and 40 minutes after the start of the infusion, at 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after the start of the docetaxel infusion. | 
| Cmax of GW572016 when given in combination with docetaxel (PK cohort 2) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 23 and Sequence 2, Day 1: Prior to the GW572016 oral dose and docetaxel infusion, at 20 and 40 minutes after the start of the infusion, at 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after the start of the docetaxel infusion | 
| Time to maximum observed plasma drug concentration (Tmax) of docetaxel alone (PK cohort 1) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 1 and Sequence 2, Day 22: Prior to the docetaxel infusion, at 20 and 40 minutes after the start of the infusion, at 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after start of the infusion. | 
| Tmax of GW572016 alone (PK cohort 2) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 1 and Sequence 2, Day 21: Prior to GW572016 dose and at 20 and 40 minutes; 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after the dose. | 
| Tmax of GW572016 when given in combination with docetaxel (PK cohort 1) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 22 and Sequence 2, Day 1: Prior to the GW572016 oral dose and docetaxel infusion, at 20 and 40 minutes after the start of the infusion, at 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after the start of the docetaxel infusion. | 
| Tmax of GW572016 when given in combination with docetaxel (PK cohort 2) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 23 and Sequence 2, Day 1: Prior to the GW572016 oral dose and docetaxel infusion, at 20 and 40 minutes after the start of the infusion, at 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after the start of the docetaxel infusion | 
| Concentration at the last measurable time point (Ctau) for GW572016 along (PK cohort 2) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 1 and Sequence 2, Day 21: Prior to GW572016 dose and at 20 and 40 minutes; 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after the dose. | 
| Time to first measurable plasma drug concentration (Tlag) for GW572016 along (PK cohort 2) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 1 and Sequence 2, Day 21: Prior to GW572016 dose and at 20 and 40 minutes; 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after the dose. | 
| AUC from time zero to time of last measurable concentration (AUClast) for docetaxel alone (PK cohort 1) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 1 and Sequence 2, Day 22: Prior to the docetaxel infusion, at 20 and 40 minutes after the start of the infusion, at 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after start of the infusion. | 
| Clearance (CL) for docetaxel alone (PK cohort 1) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 1 and Sequence 2, Day 22: Prior to the docetaxel infusion, at 20 and 40 minutes after the start of the infusion, at 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after start of the infusion. | 
| Volume of distribution at steady state (Vss) for docetaxel alone (PK cohort 1) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 1 and Sequence 2, Day 22: Prior to the docetaxel infusion, at 20 and 40 minutes after the start of the infusion, at 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after start of the infusion. | 
| Elimination half-life (Thalf) for docetaxel alone (PK cohort 1) | Blood samples will be collected at indicated time points to evaluate pharmacokinetic parameters. | Sequence 1, Day 1 and Sequence 2, Day 22: Prior to the docetaxel infusion, at 20 and 40 minutes after the start of the infusion, at 1, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, and 24 hours after start of the infusion. | 
| Number of subjects with complete response | Efficacy assessments will be obtained every three cycles depending on standard practices in specific tumor type. | Week 3 of every third cycle | 
| Number of subjects with partial response | Efficacy assessments will be obtained every three cycles depending on standard practices in specific tumor type. | Week 3 of every third cycle | 
| Number of subjects with stable disease | Efficacy assessments will be obtained every three cycles depending on standard practices in specific tumor type. | Week 3 of every third cycle | 
| Number of subjects with progressive disease | Efficacy assessments will be obtained every three cycles depending on standard practices in specific tumor type. | Week 3 of every third cycle | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tumor