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

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

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Paclitaxel 80mg/m2 weekly x 12 weeks

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 Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Breast cancer patients receiving weekly 1-hour paclitaxel infusions for curative treatment

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Weekly paclitaxel treatment group; 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.	Drug: Paclitaxel 80mg/m2 weekly x 12 weeks; Other Names: Taxol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe neuropathy	Increase in sensory scale of PRO measure of 5 points or more	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)

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Investigators: Principal Investigator: Daniel L Hertz, PharmD, PhD, University of Michigan

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): December 20, 2016
• Study Completion (Actual): December 20, 2016

Study Registration Dates

• First Submitted: January 9, 2015
• First Submitted That Met QC Criteria: January 13, 2015
• First Posted (Estimate): January 14, 2015

Study Record Updates

• Last Update Posted (Actual): May 2, 2017
• Last Update Submitted That Met QC Criteria: May 1, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: UMCC 2014.002