Topical Menthol for the Treatment of Chemotherapy Induced Peripheral Neuropathy

Study Overview
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Brief Summary
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Primary Objective: To assess whether six-week treatment with twice daily topical Menthol application will decrease neuropathic pain as measured by the change in Brief Pain Inventory-Short Form (BPI-SF worst pain score), following or during neoadjuvant/adjuvant chemotherapy with taxane or platinum-based regimens among breast, gastrointestinal or gynecologic cancer patients. Secondary objectives: To compare change in patient-reported outcomes: overall BPI-SF scales, EORTC-CIPN20, European Organization for Research and Treatment of Cancer Chemotherapy Quality of Life Questionnaire (EORTC QLQ-C30), Patient-Reported Outcomes Measurement Information System (PROMIS-29) scores between study groups. To compare changes in dose delivery and early treatment discontinuation rates between study groups. To compare objective sensory and motor functional change from baseline with the use of quantitative neurosensory testing. To perform an exploratory analysis evaluating the interaction between treatment and chemotherapy type.

Detailed Description
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Chemotherapy induced peripheral neuropathy (CIPN): CIPN is a debilitating and often irreversible toxicity associated with various chemotherapy agents widely used in the treatment of both solid tumors and hematologic malignancies. Clinical trials with Taxane-based forms of chemotherapy, commonly used in the adjuvant treatment of breast cancer, have reported up to 33% grades 2-3 sensory neuropathy and up to 14% of motor neuropathy. Severity is closely related to chemotherapy dose and schedule. CIPN may also develop in up to 64% of patients treated with 12 cycles of Oxaliplatin based adjuvant chemotherapy, when assessed clinically and electro physiologically. Patients develop an axonal, predominately sensory peripheral neuropathy, of mild to moderate severity. Thermal hyperalgesia with cold allodynia was found to be a clinical marker of early oxaliplatin neurotoxicity and may predict severe neuropathy

Official Title
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Topical Menthol for Chemotherapy Induced Peripheral Neuropathy (CIPN): A Randomized, Placebo Controlled Phase II Trial

Conditions
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Breast Cancer, Colon Cancer, Neuropathy

Intervention / Treatment
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* Drug: topical menthol
* Drug: placebo lotion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥21 years History of stage I-III breast, gastrointestinal or gynecologic cancer Must have received at least one taxane or platinum based chemotherapy drug within two years prior to enrollment. Must exhibit a typical symptom of CIPN that was not present prior to chemotherapy. Symptoms include numbness, tingling, thermal hyperalgesia, cold allodynia in the hands and/or feet, muscle weakness or unsteady gait in at least two of the last seven days prior to registration. Signed informed consent Concomitant biologic, hormonal, or radiation therapy are acceptable Narcotics, antidepressants or other medications for the treatment of CIPN are permitted, if patient on a stable dose for at least one month prior to enrollment Exclusion Criteria: Previous treatment with topical menthol (menthol/methylsalicylate products like BenGay, Aspercreme, or Icy Hot) of any concentration within the previous 3 months Known diabetic neuropathy Severe concomitant illnesses Known allergy or preexisting skin disease which prohibits use of menthol Any topical treatment for neuropathy or other serious skin condition on the hands or feet.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: topical menthol<br>Patients with neuropathic pain will receive topical menthol following or during chemotherapy for the treatment of either breast, gastrointestinal, or gynecologic cancer. | Drug: topical menthol<br>* 7.5% Methylsalicylate / 2% Menthol Lotion<br>* Other names: RX-116;|
| Active Comparator: placebo lotion<br>Patients with neuropathic pain will receive placebo lotion following or during chemotherapy for the treatment of either breast, gastrointestinal, or gynecologic cancer. | Drug: placebo lotion<br>* The control (placebo) product has same amount of Methylsalicylate (7.5%) and no menthol.<br>* Other names: RX-115;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Brief Pain Inventory-Short Form Score | The Brief Pain Inventory-Short Form (BPI-SF) is a well-validated clinical tool used frequently to assess severity of pain and its effect on daily functions in patients with neuropathy. The instrument gives several ratings of the intensity and severity of pain and the degree of pain interference on activity, mood, sleep, relations with others and work. The questionnaire uses a 0-10 scale with a higher score indicating a worse outcome. | Baseline and 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in EORTC-CIPN20 Score | The European Organization for Research and Treatment of Cancer Chemotherapy-induced peripheral neuropathy (EORTC-CIPN20) is a questionnaire measuring patient reported symptoms of chemotherapy induced neuropathy. Scores range from 20-80 with a higher score indicating a worse outcome. | Baseline and 6 weeks | 
| Change in Sensorimotor Function | Sensorimotor function as measured by a Bio-Thesiometer, which measures changes in vibratory perception. The Bio-Thesiometer is an electrical tuning fork whose amplitude can be gradually increased. Vibration threshold will be assessed at the dorsum of the distal interphalangeal joint of the index finger and dorsum of the interphalangeal joint of the hallux. Subjects will be asked to indicate when the vibration stimulus is initially felt (perception threshold) and when the stimulus disappears (disappearance threshold.) The vibration perception threshold is the average of three paired measurements. | Baseline 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chemotherapy induced neuropathy