Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Breast Cancer

Study Overview
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Brief Summary
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The primary objective of this pharmacokinetics study is to compare the maximum concentration level of paclitaxel in patients with low/sarcopenic skeletal muscle area (SMA), at the end of a 2-3 hour paclitaxel infusion, to the maximum level in patients with normal SMA at the end of a standard 1-hour infusion with the goal of determining whether lengthening the infusion in patients with low/sarcopenic SMA normalizes the levels to those of patients with normal SMA.

Detailed Description
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Paclitaxel is an FDA-approved and commonly used standard of care agent for patients with early-stage breast cancer. This study will use the standard dose of 80 mg/m^2, including the typical pre-medications as per University of Michigan Rogel Cancer Center institutional standard. The only investigational component of this study is lengthening the infusion duration from 1-hour to 2 or 3 hours for a single dose in patients with low SMA.

Official Title
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Phase IV Single-arm Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage 1-3 breast cancer Planned neoadjuvant, adjuvant, or curative intent paclitaxel 80 mg/m^2, 1-hour infusion (note: combination treatment, e.g., trastuzumab, pertuzumab, carboplatin, or pembrolizumab, and prior treatment, e.g., doxorubicin and cyclophosphamide, are allowable. Evaluable computed tomography (CT) scan, e.g., scan of the chest, abdomen, or pelvis for any indication within 1 year. Adequate organ function based on paclitaxel label. Ability to understand and the willingness to sign a written informed consent. Exclusion Criteria: Concomitant administration of any moderate or strong inducer or inhibitor of CYP2C8, including rifampin or clopidogrel. History of hypersensitivity reaction to paclitaxel or any components of paclitaxel (e.g., Cremophor EL) that precludes continued treatment with standard dose and infusion length Pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Normal SMA (>7310 mm^2)<br>Standard paclitaxel infusion time. | Drug: Paclitaxel<br>* Weekly intravenous (IV) infusion of a standard dose of paclitaxel 80 mg/m^2. Dose 1 is a 90-minute infusion. All other doses administered as a 1-hour infusion for a total of 12 weekly doses.<br>* Other names: Taxol;|
| Experimental: Low SMA (5120 - 7310 mm^2) and Sarcopenic SMA (<5120 mm^2)<br>Adjusted paclitaxel infusion time during only one dose; standard paclitaxel infusion time for all other doses. | Drug: Paclitaxel<br>* Weekly intravenous (IV) infusion of a standard dose of paclitaxel 80 mg/m^2. Dose 1 is a 90-minute infusion. During doses 2-12, patients with low SMA will receive one 2-hour infusion and patients with sarcopenic SMA will receive one 3-hour infusion. All other doses during weeks 2-12 are standard infusion time.<br>* Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration (Cmax) of paclitaxel plasma | Compare Cmax in patients with lower SMA with an adjusted infusion duration (i.e., 2-hour or 3-hour) to that of patients with normal SMA receiving standard 1-hour infusion. Blood samples for pharmacokinetic analysis will be collected within 5 minutes prior to the end of SMA-based and standard paclitaxel infusions. Measurement of plasma paclitaxel concentration for Cmax will be conducted using a liquid chromatography/mass spectroscopy assay. | Up to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Two- to three-hour Cmax vs. one-hour Cmax in low SMA patients | To compare Cmax in patients with lower SMA when receiving adjusted infusion duration (i.e., 2-hour or 3-hour) versus standard 1-hour infusion. Blood samples for pharmacokinetic analysis will be collected within 5 minutes prior to the end of SMA-based and standard paclitaxel infusions. Measurement of plasma paclitaxel concentration for Cmax will be conducted using a liquid chromatography/mass spectroscopy assay. | Up to week 12 | 
| One-hour Cmax in normal SMA patients vs. one-hour Cmax in low SMA patients | To compare Cmax in patients with lower SMA versus patients with normal SMA receiving when both receive standard 1-hour infusion. Blood samples for pharmacokinetic analysis will be collected within 5 minutes prior to the end of standard 1-hour paclitaxel infusions in both groups. Measurement of plasma paclitaxel concentration for Cmax will be conducted using a liquid chromatography/mass spectroscopy assay. | Up to week 12 | 

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