Low Accrual Rate

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.

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.

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

Confidentiality is an issue.

All adverse events (AE's) regardless of grade or attribution will be recorded from the beginning of study treatment (Cycle 1, Day 1 of nicotine transdermal patch administration) through the 30-day follow-up period.

The Coronavirus-19 (COVID-19) pandemic caused reduced accrual rates. The protocol was terminated early due to slow accrual rates by the Protocol Review & Monitoring Committee (PRMC).