Paclitaxel Therapeutic Drug Monitoring in Cancer Patients

Sponsor

Wake Forest University Health Sciences (Other)

Overall Status

Recruiting

CT.gov ID

NCT03987555

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

43.6

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goals of this prospective, observational cohort study are to determine the feasibility of implementing paclitaxel therapeutic drug monitoring for cancer patients and explore the relationship between paclitaxel drug exposure and the development of neuropathic symptoms.

This trial studies if paclitaxel can be consistently measured in the blood of patients with solid tumors undergoing paclitaxel treatment. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Nerve damage is one of the most common and severe side effects of paclitaxel. The ability to consistently measure paclitaxel in the blood may allow doctors to control the dose of paclitaxel, so that enough chemotherapy is given to kill the cancer, but the side effect of nerve damage is reduced.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor, Adult Metastatic Nonsmall Cell Lung Cancer Anatomic Stage IV Breast Cancer AJCC v8 Metastatic Cervical Carcinoma Metastatic Ovarian Carcinoma Malignant Uterine Neoplasm Vulvar Cancer Invasive Breast Cancer Metastatic Breast Carcinoma Prognostic Stage IV Breast Cancer AJCC v8 Recurrent Breast Carcinoma Recurrent Cervical Carcinoma Recurrent Lung Non-Small Cell Carcinoma Recurrent Ovarian Carcinoma Recurrent Vulvar Carcinoma Stage IV Cervical Cancer AJCC v8 Stage IV Lung Cancer AJCC v8 Stage IV Vulvar Cancer AJCC v8 Stage IV Ovarian Cancer AJCC v8 Stage IVA Cervical Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVA Ovarian Cancer AJCC v8 Stage IVA Vulvar Cancer AJCC v8 Stage IVB Cervical Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8 Stage IVB Ovarian Cancer AJCC v8 Stage IVB Vulvar Cancer AJCC v8 Vulva Squamous Cell Carcinoma	Other: Blood draws Other: QLQ-CIPN20 Survey Other: PR-CTCAE Survey

Detailed Description

Primary Objective:

• Determine the feasibility of monitoring paclitaxel serum drug levels in patients with a solid tumor (e.g. lung, breast, and gynecologic cancers) for which Paclitaxel is the standard of care.

Secondary Objectives:

Compare Paclitaxel serum drug levels among patients with differing degrees of chemotherapy-induced peripheral neuropathy at the end of Paclitaxel treatment.
Compare mitochondrial function within circulating peripheral blood mononuclear cells among patients with differing degrees of chemotherapy-induced peripheral neuropathy at the end of Paclitaxel treatment.
Compare the ability of pulsed electromagnetic field to modulate immune cells of individuals experiencing differing degrees of chemotherapy-induced peripheral neuropathy at the end of Paclitaxel treatment.

Study Design

Study Type:

Observational

Anticipated Enrollment :

20 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Pilot Feasibility Study of Paclitaxel Therapeutic Drug Monitoring in Cancer Patients

Actual Study Start Date :

Nov 11, 2019

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Jul 1, 2023

Outcome Measures

Primary Outcome Measures

Proportion of Participants Completing Paclitaxel Infusions [One day after last infusion dose]
Feasibility will be assessed based on the proportion of patients who complete study blood draws at >90% of completed Paclitaxel infusions. A completed Paclitaxel infusion is defined as each dose of Paclitaxel that is completed in its entirety. The a priori success rate will be defined as 90% of patients receiving 100% of study blood draws and the null rate will be set at 50%

Secondary Outcome Measures

Differences in Maximum Plasma Concentration of Paclitaxel from Baseline to Completion [30 days after completion of chemotherapy treatment]
Differences in descriptive characteristics (e.g. mean, median, standard deviation, etc.) of the Paclitaxel maximum plasma concentration (Cmax) among patients with and without chemotherapy-induced peripheral neuropathy according to the physician reported neuropathy CTCAE (Grade II or greater) at baseline and at the end of Paclitaxel treatment.
Differences in Time Above Threshold from Baseline to Completion [30 days after completion of chemotherapy treatment]
Differences in descriptive characteristics (e.g. mean, median, standard deviation, etc.) of time above threshold (Tc>0.05) among patients with and without chemotherapy-induced peripheral neuropathy according to the physician reported neuropathy CTCAE (Grade II or greater) at baseline and at the end of Paclitaxel treatment.
Differences in Inflammasome Activation from Baseline to Completion [30 days after completion of chemotherapy treatment]
Differences in inflammasome activation following pulsed electromagnetic field stimulation between patients with and without chemotherapy-induced peripheral neuropathy according to the physician reported neuropathy CTCAE at baseline and at the end of Paclitaxel treatment.
Differences in Inflammatory Cytokine Production from Baseline to Completion [30 days after completion of chemotherapy treatment]
Differences in inflammatory cytokine production following pulsed electromagnetic field stimulation between patients with and without chemotherapy-induced peripheral neuropathy according to the physician reported neuropathy CTCAE at baseline and at the end of Paclitaxel treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female sex
Age ≥ 18 years
Individuals receiving treatment at the Wake Forest Comprehensive Cancer Center who are anticipated to receive paclitaxel for curative or palliative intent, with or without surgery and/or radiation (i.e. neoadjuvant, adjuvant, or in the setting of recurrent or metastatic disease) as per decision with their medical oncologist for the following malignancies and dosing regimens:
Invasive breast cancer (any HER2 and ER/PR status)
Patients considered for curative or palliative chemotherapy with paclitaxel 80-175 mg/m2 with or without doxorubicin, cyclophosphamide, carboplatin, trastuzumab, bevacizumab, or pertuzumab

Cervical cancer • Patients considered for curative or palliative chemotherapy with paclitaxel 135-175 mg/m2 with or without cisplatin, carboplatin, topotecan, or bevacizumab

Non-small cell lung cancer

• Patients considered for curative or palliative chemotherapy with paclitaxel 45-200 mg/m2 with or without carboplatin, cisplatin, bevacizumab, atezolizumab, or pembrolizumab

Ovarian cancer • Patients considered for curative or palliative chemotherapy with paclitaxel 60-175 mg/m2 with or without carboplatin, cisplatin, ifosfamide, gemcitabine, pazopanib, or bevacizumab

Uterine neoplasms

• Patients considered for curative or palliative chemotherapy with paclitaxel 135-175 mg/m2 with or without carboplatin, cisplatin, doxorubicin, ifosfamide, bevacizumab, or trastuzumab

Vulvar cancer (squamous cell carcinoma)

Patients considered for curative or palliative chemotherapy with paclitaxel 60-175 mg/m2 with or without cisplatin, carboplatin, or bevacizumab
Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative)
Patients with prior radiation treatment or surgery will not be disqualified from enrollment into the study, unless the aforementioned interventions resulted in peripheral neuropathy as a complication

Exclusion Criteria:

Prior treatment with PTX, for any duration or indication
Prior treatment with neurotoxic chemotherapy including any taxane, vinca alkaloid, platinum-containing agent, bortezomib, or thalidomide that has resulted in clinical symptoms of persistent, CTCAE grade II or higher peripheral neuropathy
Concurrent enrollment in a clinical study of a neuroprotective intervention at the time of study initiation
Any contraindication to Paclitaxel (e.g. history of allergic reaction to paclitaxel or Kolliphor EL)
Current signs or symptoms of peripheral neuropathy at the time of enrollment, e.g. due to diabetes, HIV, or other conditions
Known personal or family history of hereditary peripheral neuropathy (e.g. Charcot-Marie-Tooth disease)