Study of Nicotine for Pain Associated With Chemotherapy-Induced Peripheral Neuropathy

Phase 2 Study of Nicotine for the Treatment of Pain Associated With Chemotherapy-Induced Peripheral Neuropathy

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