Topical Cannabidiol for the Treatment of Chemotherapy-Induced Peripheral Neuropathy

• ClinicalTrials.gov Identifier: NCT05388058
• Recruitment Status: Recruiting
• First Posted: May 24, 2022
• Last Update Posted: January 6, 2023
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): Mayo Clinic

Tracking Information

• First Submitted Date: May 19, 2022
• First Posted Date: May 24, 2022
• Last Update Posted Date: January 6, 2023
• Actual Study Start Date: June 9, 2022
• Estimated Primary Completion Date: April 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 19, 2022)

Change in chemotherapy-induced peripheral neuropathy (CIPN) [ Time Frame: Baseline to end of week 2 ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 19, 2022)

• Change in EORTC QLQ CIPN20 motor subscale [ Time Frame: Baseline to end of week 2 ]
  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.
• Change in EORTC QLQ CIPN20 autonomic scale [ Time Frame: Baseline to end of week 2 ]
  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.
• Total Common Terminology Criteria for Adverse Events (CTCAE) neuropathy scale [ Time Frame: Up to 14 days ]
  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.
• Incidence of adverse events [ Time Frame: Up to 28 days ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Supportive Care

Condition

• Chemotherapy-Induced Peripheral Neuropathy
• Malignant Solid Neoplasm

Intervention

• Drug: Cannabidiol
  Applied topically
  Other Names:

  • CBD
  • CBD Oil
  • Epidiolex
  • GWP42003-P
• Drug: Placebo Administration
  Applied topically
• Other: Quality-of-Life Assessment
  Ancillary studies
  Other Name: Quality of Life Assessment
• Other: Questionnaire Administration
  Ancillary studies

Study Arms

• Experimental: Arm I (cannabidiol, placebo)
  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.
  Interventions:

  • Drug: Cannabidiol
  • Drug: Placebo Administration
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration
• Experimental: Arm II (placebo, cannabidiol)
  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.
  Interventions:

  • Drug: Cannabidiol
  • Drug: Placebo Administration
  • Other: Quality-of-Life Assessment
  • Other: Questionnaire Administration

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 19, 2022): 40
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: April 1, 2024
• Estimated Primary Completion Date: April 1, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05388058
• Other Study ID Numbers: MC211003; NCI-2022-02479 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Mayo Clinic
• Original Responsible Party: Same as current
• Current Study Sponsor: Mayo Clinic
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Stacy D D'Andre; Mayo Clinic in Rochester

• PRS Account: Mayo Clinic
• Verification Date: July 2022