Defining an Exposure Target for Weekly Paclitaxel Infusion in Breast Cancer Patients

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Paclitaxel 80mg/m2 weekly x 12 weeks

• Registration Number: NCT02338115
• Lead Sponsor: University of Michigan Rogel Cancer Center

Brief Summary

The purpose of this prospective observational study is to understand the relationship between paclitaxel exposure and development of peripheral neuropathy during treatment.

Detailed Description

Paclitaxel is a chemotherapeutic agent commonly used in various tumor types. Paclitaxel efficacy and toxicity are "dose-dependent" meaning that increasing the dose increases treatment efficacy and occurrence of toxicity. When used in the weekly 1-hour infusion regimen paclitaxel is commonly associated with treatment-limiting sensory peripheral neuropathy. At the current standard dose of 80 mg/m2 approximately 20-25% of patients experience treatment-limiting neuropathy.

Drug exposure, not dose, determines treatment efficacy and neuropathy development. When treated with standard doses there is substantial variability in drug exposure meaning some patients are receiving less efficacious treatment than optimal. At this time we do not monitor a patient's exposure because the optimal exposure level has not been defined. The purpose of this study is to prospectively enroll patients for systematic collection of exposure and neuropathy data in order to characterize this relationship. Once the relationship between cumulative exposure and neuropathy has been characterized, this model will be used to define an exposure target in future prospective exposure-guided dose-adjustment trials.

Study Timeline

• Study Start: 2014-05
• Study First Submitted: 2015-01-09
• Study First Submitted QC: 2015-01-13
• Study First Posted: 2015-01-14
• Primary Completion: 2016-12-20
• Study Completion: 2016-12-20
• Status Verified: 2017-05
• Last Update Submitted: 2017-05-01
• Last Update Posted: 2017-05-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 60

Inclusion Criteria

• Diagnosis of invasive breast cancer

• Systemic treatment with paclitaxel for curative intent (neoadjuvant, adjuvant, or oligometastatic disease per PI discretion)

• 80 mg/m2 1-hour infusions weekly for up to 12 weeks

• Female sex

  ->18 years old

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

Exclusion Criteria

• Any prior or concurrent treatment with neurotoxic chemotherapy including any taxane, vinca alkaloid, platinum, bortezomib, or thalidomide. Note that concurrent biologic treatment with trastuzumab/pertuzumab for HER2+ patients or prior treatment with Adriamycin/cyclophosphamide are not reasons for exclusion.
• Distant metastatic disease
• Concurrent treatment with duloxetine or enrollment on clinical study of neuroprotective agent
• History of allergic reaction to paclitaxel or cremophor EL
• Current signs or symptoms of severe peripheral neuropathy
• Known family history of hereditary peripheral neuropathy or Charcot-Marie-Tooth disease
• Known current pregnancy

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Weekly paclitaxel treatment group	Paclitaxel 80mg/m2 weekly x 12 weeks	Breast cancer patients initiating paclitaxel 80mg/m2 weekly x 12 weeks for curative treatment will be followed prospectively for collection of samples and longitudinal neuropathy data.

Primary Outcome Measures

Name	Time	Method
Severe neuropathy	During 12 cycles of paclitaxel treatment (12 weeks for most patients but longer for patients who have treatment delays. Expected maximum 16 weeks of treatment)	Increase in sensory scale of PRO measure of 5 points or more

Trial Locations

Locations (1)

University of Michigan Comprehensive Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States