Clinical trial NCT02338115: Defining an Exposure Target for Weekly Paclitaxel Infusion in Breast Cancer Patients
Official title: Defining an Exposure Target for Weekly Paclitaxel Infusion in Breast Cancer Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Breast Cancer
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2015-01-14
Enrollment: 60
Sex: FEMALE
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Breast cancer patients receiving weekly 1-hour paclitaxel infusions for curative treatment

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.

Eligibility criteria: 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

Primary outcomes:
measure: Severe neuropathy
timeFrame: 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)
Secondary outcomes:
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
Study officials:
affiliation: University of Michigan
name: Daniel L Hertz, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
References: