Topical Cannabidiol for the Treatment of Chemotherapy-Induced Peripheral Neuropathy

Study Overview
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Brief Summary
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This clinical trial compares topical cannabidiol to placebo in improving chemotherapy-induced peripheral neuropathy, or painful sensations in your hands or feet due to chemotherapy. Peripheral neuropathy is a nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in different parts of the body. It usually begins in the hands or feet and gets worse over time. Peripheral neuropathy caused by chemotherapy is called chemotherapy-induced peripheral neuropathy (CIPN). CIPN is commonly seen in patients receiving certain chemotherapy medications and is hard to treat. Medications commonly used to treat CIPN have limited benefits and may cause significant side effects. A small report showed that topical cannabidiol may help treat neuropathy in patients with diabetes. This study is being done to determine if cannabidiol cream can help improve the symptoms of CIPN.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate whether topical cannabidiol (CBD) improves CIPN, compared to placebo. II. To evaluate side effects from topical CBD cream use, compared to placebo. SECONDARY OBJECTIVES: I. Other measures of neuropathy as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) CIPN20 motor subscale, the EORTC QLQ CIPN20 autonomic scale, and the total Common Terminology Criteria for Adverse Events (CTCAE) neuropathy scale. II. Adverse event profiles will also be assessed using symptom questionnaires and CTCAE version (v)5.0. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients apply cannabidiol cream topically to affected areas twice daily (BID) for 14 days. Patients then apply placebo cream topically to affected areas BID for 14 days. ARM II: Patients apply placebo cream topically to affected areas BID for 14 days. Patients then apply cannabidiol cream topically to affected areas BID for 14 days.

Official Title
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Topical Cannabidiol (CBD) for the Treatment of Chemotherapy-Induced Peripheral Neuropathy: A Randomized Placebo-Controlled Pilot Trial

Conditions
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Chemotherapy-Induced Peripheral Neuropathy, Malignant Solid Neoplasm

Intervention / Treatment
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* Drug: Cannabidiol
* Drug: Placebo Administration
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 years English speaking Cancer diagnosis of any tumor type with chemotherapy-induced neuropathy At least 4 out of 10 severity of neuropathy pain and/or tingling Stable for at least 7 days prior to registration on medications for neuropathy, if any are being used Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 Negative pregnancy test done =< 7 days prior to registration, for persons of childbearing potential only NOTE: If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required Able to provide written informed consent Ability to complete questionnaire(s) by themselves or with assistance No evidence of residual cancer Platelet count > 100,000/mm^3 (following completion of chemotherapy) Absolute neutrophil count (ANC) >= 1,000/mm^3 (following completion of chemotherapy) Hemoglobin > 11 g/dL (following completion of chemotherapy) Serum transaminase (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) =< 1.2 x upper limit of normal (ULN) (following completion of chemotherapy) Alkaline phosphatase =< 1.2 x ULN (following completion of chemotherapy) Serum creatinine =< 1.2 x ULN (following completion of chemotherapy) Exclusion Criteria: Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: Pregnant persons Nursing persons Persons of childbearing potential who are unwilling to employ adequate contraception Any medical condition that would prohibit use of a topical cream (skin infection or open wound in the area of the neuropathy) Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens Pre-existing neuropathy prior to chemotherapy that would confuse the issue of CIPN Currently on chemotherapy or received chemotherapy treatment within the prior 3 months Use of other cannabis products within 30 days prior to registration History of allergy to cannabis products

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (cannabidiol, placebo)<br>Patients apply cannabidiol cream topically to affected areas BID for 14 days. Patients then apply placebo cream topically to affected areas BID for 14 days. | Drug: Cannabidiol<br>* Applied topically<br>* Other names: GWP42003-P;Drug: Placebo Administration<br>* Applied topically<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Experimental: Arm II (placebo, cannabidiol)<br>Patients apply placebo cream topically to affected areas BID for 14 days. Patients then apply cannabidiol cream topically to affected areas BID for 14 days. | Drug: Cannabidiol<br>* Applied topically<br>* Other names: GWP42003-P;Drug: Placebo Administration<br>* Applied topically<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in chemotherapy-induced peripheral neuropathy (CIPN) | CIPN will be measured by the sensory subscale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-CIPN20 which is composed of 9 individual items. Will be compared between arms using two-sample, two-sided t-tests. The cannabidiol arm will be compared to the placebo arm. Will construct 95% confidence intervals for the mean difference in sensory neuropathy score between arms. Repeated measures mixed models will be applied to the sensory scores over all time points to determine longitudinal effects and to adjust for confounding factors. Graphical results will include profile plots over time, stream plots of individual changes over time, and forest plots of the 95% confidence intervals by arm. | Baseline to end of week 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in EORTC QLQ CIPN20 motor subscale | Will be compared between arms using two-sample, two-sided t-tests. The cannabidiol arm will be compared to the placebo arm. Will construct 95% confidence intervals for the mean difference in sensory neuropathy score between arms. Repeated measures mixed models will be applied to the sensory scores over all time points to determine longitudinal effects and to adjust for confounding factors. Graphical results will include profile plots over time, stream plots of individual changes over time, and forest plots of the 95% confidence intervals by arm. | Baseline to end of week 2 | 
| Change in EORTC QLQ CIPN20 autonomic scale | Will be compared between arms using two-sample, two-sided t-tests. The cannabidiol arm will be compared to the placebo arm. Will construct 95% confidence intervals for the mean difference in sensory neuropathy score between arms. Repeated measures mixed models will be applied to the sensory scores over all time points to determine longitudinal effects and to adjust for confounding factors. Graphical results will include profile plots over time, stream plots of individual changes over time, and forest plots of the 95% confidence intervals by arm. | Baseline to end of week 2 | 
| Total Common Terminology Criteria for Adverse Events (CTCAE) neuropathy scale | Will compare the incidence and maximum (worst) values between arms. Fisher's exact tests will be used to compare incidence rates and Wilcoxon rank-sum tests will be used to compare maximum values between arms. | Up to 14 days | 
| Incidence of adverse events | Will be assessed using symptom questionnaires and CTCAE version 5.0. Will compare the incidence and maximum (worst) values between arms. Fisher's exact tests will be used to compare incidence rates and Wilcoxon rank-sum tests will be used to compare maximum values between arms. | Up to 28 days |