Paclitaxel Therapeutic Drug Monitoring in Cancer Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Pilot Feasibility Study of Paclitaxel Therapeutic Drug Monitoring in Cancer Patients

Conditions
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Solid Tumor, Adult, Malignant Uterine Neoplasm, Metastatic Nonsmall Cell Lung Cancer, Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Cervical Carcinoma, Metastatic Ovarian Carcinoma, 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

Intervention / Treatment
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* Other: Blood draws
* Other: QLQ-CIPN20 Survey
* Other: PR-CTCAE Survey


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Blood draws|Blood draws for serum and peripheral blood mononuclear cell isolation collected throughout treatment course|
|Other: QLQ-CIPN20 Survey|20-item self-reported survey for participant reported symptoms related to chemotherapy-induced peripheral neuropathy|
|Other: PR-CTCAE Survey|124-item survey addressing chemotherapy-induced peripheral neuropathy concerning severity of the numbness and tingling and the degree these symptoms interfere with daily activities.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Completing Paclitaxel Infusions | 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% | One day after last infusion dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in Maximum Plasma Concentration of Paclitaxel from Baseline to Completion | 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. | 30 days after completion of chemotherapy treatment | 
| Differences in Time Above Threshold from Baseline to Completion | 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. | 30 days after completion of chemotherapy treatment | 
| Differences in Inflammasome Activation from Baseline to Completion | 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. | 30 days after completion of chemotherapy treatment | 
| Differences in Inflammatory Cytokine Production from Baseline to Completion | 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. | 30 days after completion of chemotherapy treatment |