Clinical trial NCT03987555: Paclitaxel Therapeutic Drug Monitoring in Cancer Patients
Official title: Pilot Feasibility Study of Paclitaxel Therapeutic Drug Monitoring in Cancer Patients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: 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
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2019-06-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This study is designed to enroll male and female patients with histologically-confirmed solid tumors who are anticipated to receive Paclitaxel as part of the curative or palliative antineoplastic therapy. The study will target lung, breast, and gynecologic (i.e. cervical, ovarian, uterine, and vulvar) cancers specifically.

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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Proportion of Participants Completing Paclitaxel Infusions
timeFrame: One day after last infusion dose
Secondary outcomes:
measure: Differences in Maximum Plasma Concentration of Paclitaxel from Baseline to Completion
timeFrame: 30 days after completion of chemotherapy treatment
measure: Differences in Time Above Threshold from Baseline to Completion
timeFrame: 30 days after completion of chemotherapy treatment
measure: Differences in Inflammasome Activation from Baseline to Completion
timeFrame: 30 days after completion of chemotherapy treatment
measure: Differences in Inflammatory Cytokine Production from Baseline to Completion
timeFrame: 30 days after completion of chemotherapy treatment
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Roy Strowd, MD
role: PRINCIPAL_INVESTIGATOR
References: