Remote Monitoring and Management of Chemotherapy Induced Peripheral Neuropathy

This is a prospective single blinded (outcome assessor) randomized controlled trial of a CIPN care model that pairs a personalized suite of remote symptom monitoring technologies with triggered real time responses from a nurse practitioner (NP) equipped to enact algorithmic guideline based CIPN treatment in response to poorly controlled symptoms. The study will enroll adult cancer patients who have, within the last 540 days, completed a course of a taxane, platinum, or vinca alkaloid-based agent, bortezomib, thalidomide, lenalidomide, ixazomib or brentuximab vedotin, or have been receiving ongoing maintenance therapy with bortezomib, thalidomide, lenalidomide or ixazomib for >90 days, and have been diagnosed with CIPN. Participants will log neuropathy symptoms daily for a one week run-in period using a remote symptom monitoring technology described below. Participants who meet the criteria to proceed in the study will be randomized in a 1:1 ratio to Usual Care (UC) or Symptom Care at Home with Nurse Practitioner follow up (SCH-NP). Those not meeting eligibility criteria will be excluded but can be rescreened 6 weeks later. Both groups will log symptoms daily and receive either UC or SCH-NP care for the 12 week study period.

The UC group will report daily neuropathy symptoms via the web, app or automated phone system and will receive usual care for CIPN symptoms from their existing treatment team. The SCH-NP group will report symptoms similarly but concerning symptoms will trigger a call back from a nurse practitioner who can provide treatment based on standardized algorithmic CIPN guidelines.

In person study visits will take place at baseline and 6 and 12 weeks after randomization. CIPN specific QoL and disability measures, validated CIPN sign scales and detailed information on opioids, neuropathic pain medications and other CIPN treatments will be collected at each visit.

Inclusion criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• Age ≥ 18.
• Completion of taxane, platinum, vinca alkaloid-based chemotherapy, bortezomib, thalidomide, lenalidomide, ixazomib, or brentuximab vedotin for cancer in the last 540 days, or ongoing maintenance therapy with bortezomib, thalidomide, lenalidomide or ixazomib for > 90 days or ongoing survival, palliative or equivalent therapy with any of the above listed drugs for >90 days.
• Development of CIPN during or within 3 months of the most recently completed chemotherapy or previous neurotoxic chemotherapy for the same malignancy. For patients on ongoing maintenance therapy: Development of CIPN during current neurotoxic chemotherapy with bortezomib, thalidomide, lenalidomide, ixazomib brentuximab vendotin or vincristine. CIPN diagnosis will be based on clinical diagnosis and the Toronto Criteria for Probable Distal Symmetric Polyneuropathy including the upper and lower extremities.

The Toronto Criteria for Probable Distal Symmetric Polyneuropathy is defined as a combination of symptoms and signs of neuropathy including:

• At least 1 (one) of the following neuropathic symptoms: "asleep numbness", prickling or stabbing, burning or aching pain AND
• At least 1 (one) of the following: decreased distal sensation, or unequivocally decreased or absent ankle reflexes. (59)

Clinical Diagnosis:

a. Confirmation of CIPN diagnosis by CIPN expert (investigator/co-infestigator based on chart review +/- inperson/virtual interview with examination).

• Presence of at least one positive neuropathic sensory symptom on the NTSS-6 ranked as moderate or severe on the day of screening or in the preceding week based on recall.
• The ability to speak/ read sufficient English to be able to communicate with study NP over the phone, utilize the App, website and phone tree (all of which are only available in English).

Exclusion criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

• Expected treatment with another neurotoxic chemotherapy within the 13 week overall study duration (For example, platinum, taxane, vinca alkaloid, thalidomide, brentuximab vedotin or related drug, or arsenic trioxide. This exclusion does not apply to continuation of treatment for patients on maintenance therapy as described in the inclusion criteria).
• Presence of a neurological problem that would confound CIPN assessment (lumbar or cervical radiculopathy, or pre-existing neuropathy from another cause such as diabetes).
• Currently receiving treatment at a pain clinic specifically for CIPN pain.
• Concurrent participation in a different CIPN or pain treatment trial.
• For women of childbearing potential: Current pregnancy
• For women of childbearing potential: Unwillingness to use and acceptable form of birth control for the duration of the study. Acceptable forms of birth control include long acting implantable contraception (ie IUDs, Nexplanon), Oral contraception pills, contraception injections, or strict abstinence if it is part of the subject's current lifestyle.