Chemotherapy-induced Peripheral Neuropathy, Neuropathic Pain, Neuropathy, Peripheral Neuropathy
Conditions
Keywords
Nicotine, Peripheral Neuropathy
Brief summary
Assess the efficacy of short-term nicotine transdermal patch administration for the treatment of chemotherapy-induced peripheral neuropathy (CIPN) in cancer stable patients or patients in remission.
Detailed description
This phase 2 study will test the efficacy of short-term transdermal nicotine transdermal patch administration in patients who have been diagnosed with CIPN. The study will follow an open-label, crossover within-subjects clinical trial design with nicotine transdermal patch.
Interventions
Nicotine Treatment Condition
Sponsors
Virginia Commonwealth University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinically diagnosed peripheral sensory neuropathy defined as: * Greater than Grade 1 peripheral sensory neuropathy using the CTCAE v5.0 grading scale * Grade 1 Asymptomatic * Grade 2 Moderate symptoms; limiting instrumental activities of daily living (ADL) * Grade 3 Severe symptoms; limiting self-care ADL * Grade 4 Life-threatening consequences; urgent intervention indicated * Have a baseline chemotherapy-induced peripheral neuropathy (CIPN) patient reported outcome (PRO) total sensory score ≥ 24.3 on a 19 to 76 scale using the European Organization for Research and Treatment of Cancer Quality of Life-CIPN20 Questionnaire (EORTC QLQ-CIPN-20) * Have a CIPN-related neuropathic pain score ≥ 4 on a 0 to 10 scale using the Brief Pain Inventory-Short Form (BPI-SF) item 5 * Will not have used any nicotine or tobacco products (eg, cigarettes, electronic cigarettes, smokeless tobacco, or other nicotine replacement therapies) within 14 days prior to study treatment start date * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Not currently receiving any chemotherapy * Have previously received platinum- and/or taxane-based chemotherapy treatments and have persistent pain at least 3 months after completion of treatments. * Willing and able to comply with study procedures and visit schedule. * Willing to abstain from all tobacco/nicotine product use during study treatment and 30-day follow-up period. * Ability to self-apply or have the patch applied at home daily. * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* History of pre-existing peripheral sensory neuropathies related to the following: * Autoimmune disease * B12/folate deficiency * Diabetes Mellitus * Human immunodeficiency virus (HIV) * Hyper/hypothyroidism * Monoclonal gammopathy of undetermined significance or multiple myeloma * History of receiving other types of neurotoxic chemotherapy drugs (eg, vinca alkaloids, bortezomib, thalidomide) * Current or prior pheochromocytoma * History of or active or clinically significant cardiac disease including any of the following: * Unstable angina (eg, anginal symptoms at rest) or onset of angina within 3 months prior to initiating study treatment * Myocardial infarction diagnosed within 6 months prior to initiating study treatment * Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers * New York Heart Association (NYHA) class III or IV congestive heart failure * Poorly controlled high or low blood pressure defined as: * Systolic blood pressure (SBP) ≥ 140; Diastolic blood pressure (DBP) ≥ 90 * SBP ≤ 90; DBP ≤ 60 * Regular use of the following medications: * Varenicline * Bupropion (ie, bupropion hydrochloride sustained release) * Women will be excluded if they are breastfeeding or are pregnant (by urinalysis) within 14 days prior to the start of nicotine transdermal patch administration. * Medical, psychological, or social condition that, in the opinion of the investigator, may increase the patient's risk or limit the patient's adherence with study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Short-term Nicotine Transdermal Patch Administration in the Treatment of Cancer Induced Peripheral Neuropathy (CIPN) | 79 Days | To assess the efficacy, of the nicotine transdermal patch administration in the treatment of CIPN in patients whose cancer is stable or in remission as defined by a ≥ 2.7 point decrease in the total sensory score of the European Organization for Research and Treatment of Cancer Quality of Life-cancer induced peripheral neuropathy (CIPN20) Questionnaire (EORTC QLQ-CIPN-20) (eg, an improvement in the patients quality of life by one grade). The QLQ-CIPN20 numerical score has a range of 19-76, in which lower scores indicate less symptoms and a better quality of life. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Pain-related Changes and Degree of Functional Interference in the Treatment of CIPN | 79 Days | To assess the efficacy of short-term nicotine transdermal patch administration in the treatment of CIPN in patients whose cancer is stable or in remission by assessing changes in the degree of pain-related functional interference measured by the Brief Pain Inventory - Short Form (BPI-SF) interference score. The BPI-SF contains 4 items assessing average, worst, least, and immediate pain severity in the last 24 hours. Pain severity items are scored using an 11-point numeric rating scale (0, no pain; 10, pain as bad as you can imagine). Seven BPI-SF items will be used to quantify the degree to which pain interferes with daily activities or function (0, does not interfere; 10, completely interferes). The 7 items are summed to obtain a total interference score. |
| Number of Participants at Risk and Affected by Adverse Events (AEs) Related to the Transdermal Nicotine Patch. | 79 Days | To assess the AEs profile of nicotine transdermal patch administration for the treatment of CIPN in patients whose cancer is stable or in remission. The Adverse events (AEs) are reported using criteria in the National Cancer Institute Common Terminology Criteria for Adverse Events Version (CTCAE v 5.0) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nicotine Transdermal Patch Administration Each patient will complete two 14-day treatment conditions, for 7 mg nicotine transdermal patch administration with a washout period in between (≥ 14 days and up to 21 days), then 14 mg nicotine transdermal patch administration (14 days).
Nicotine Transdermal Patch: Nicotine Treatment Condition | 0 |
| Total | 0 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Efficacy of Short-term Nicotine Transdermal Patch Administration in the Treatment of Cancer Induced Peripheral Neuropathy (CIPN)
To assess the efficacy, of the nicotine transdermal patch administration in the treatment of CIPN in patients whose cancer is stable or in remission as defined by a ≥ 2.7 point decrease in the total sensory score of the European Organization for Research and Treatment of Cancer Quality of Life-cancer induced peripheral neuropathy (CIPN20) Questionnaire (EORTC QLQ-CIPN-20) (eg, an improvement in the patients quality of life by one grade). The QLQ-CIPN20 numerical score has a range of 19-76, in which lower scores indicate less symptoms and a better quality of life.
Time frame: 79 Days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotine Transdermal Patch Administration | Efficacy of Short-term Nicotine Transdermal Patch Administration in the Treatment of Cancer Induced Peripheral Neuropathy (CIPN) | 7mg patch | -7.7 score on a scale | Standard Deviation 10.5 |
| Nicotine Transdermal Patch Administration | Efficacy of Short-term Nicotine Transdermal Patch Administration in the Treatment of Cancer Induced Peripheral Neuropathy (CIPN) | 14 mg patch | -2.0 score on a scale | Standard Deviation 5 |
Secondary
Efficacy of Pain-related Changes and Degree of Functional Interference in the Treatment of CIPN
To assess the efficacy of short-term nicotine transdermal patch administration in the treatment of CIPN in patients whose cancer is stable or in remission by assessing changes in the degree of pain-related functional interference measured by the Brief Pain Inventory - Short Form (BPI-SF) interference score. The BPI-SF contains 4 items assessing average, worst, least, and immediate pain severity in the last 24 hours. Pain severity items are scored using an 11-point numeric rating scale (0, no pain; 10, pain as bad as you can imagine). Seven BPI-SF items will be used to quantify the degree to which pain interferes with daily activities or function (0, does not interfere; 10, completely interferes). The 7 items are summed to obtain a total interference score.
Time frame: 79 Days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nicotine Transdermal Patch Administration | Efficacy of Pain-related Changes and Degree of Functional Interference in the Treatment of CIPN | 7 mg patch | -1.3 score on a scale | Standard Deviation 2.1 |
| Nicotine Transdermal Patch Administration | Efficacy of Pain-related Changes and Degree of Functional Interference in the Treatment of CIPN | 14 mg patch | -2.0 score on a scale | Standard Deviation 1.7 |
Secondary
Number of Participants at Risk and Affected by Adverse Events (AEs) Related to the Transdermal Nicotine Patch.
To assess the AEs profile of nicotine transdermal patch administration for the treatment of CIPN in patients whose cancer is stable or in remission. The Adverse events (AEs) are reported using criteria in the National Cancer Institute Common Terminology Criteria for Adverse Events Version (CTCAE v 5.0)
Time frame: 79 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nicotine Transdermal Patch Administration | Number of Participants at Risk and Affected by Adverse Events (AEs) Related to the Transdermal Nicotine Patch. | 4 Participants |