PEA for the Relief of Chemotherapy-Induced Peripheral Neuropathy

Malignant Solid Neoplasm Clinical Trial

Official title:

Treatment of Established Chemotherapy-Induced Neuropathy With N-Palmitoylethanolamide, a Cannabimimetic Nutraceutical: A Randomized Double-Blind Phase II Pilot Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05246670
• Other study ID #: ACCRU-SC-2102
• Secondary ID: NCI-2022-00002AC
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 16, 2022
• Est. completion date: February 28, 2025

Study information

• Verified date: October 2023
• Source: Academic and Community Cancer Research United
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial tests whether PEA works to relieve the symptoms of chemotherapy-induced peripheral neuropathy in patients with cancer. Chemotherapy-induced peripheral neuropathy refers to a nerve problem that causes pain, numbness, tingling, or muscle weakness in different parts of the body, and is caused by chemotherapy. PEA may be useful against bothersome nerve symptoms.

Description:

PRIMARY OBJECTIVE: I. To look for evidence of the efficacy of PEA (N-palmitoylethanolamide) at two different doses relative to placebo responses, as a treatment for chemotherapy-induced neuropathy (CIPN). SECONDARY OBJECTIVES: I. To assess the safety of PEA at the two study doses. II. To evaluate changes in patient-reported quality of life from baseline to the end of 8 weeks. EXPLORATORY OBJECTIVES: I. To explore whether PEA appears to affect cognition in the study patients. II. To explore the weekly trajectory of CIPN from baseline to 8 weeks. III. To explore the weekly trajectory of pain using the single-item numerical rating scale from baseline to 8 weeks. IV. To explore the weekly patient global impression of change in each treatment arm from baseline to 8 weeks. V. To explore the weekly chemotherapy induced peripheral neuropathy in each treatment arm from baseline to 8 weeks. VI. To explore the PEA effects on CIPN20 between two PEA dosage arms. VII. To explore the number of recurrent cancer events by study arm. VIII. To explore the overall survival by study arm. OUTLINE: Patients are randomized to 1 of 4 arms. ARM I: Patients receive PEA orally (PO) once daily (QD) for 8 weeks as long as there is not any unacceptable toxicity. ARM II: Patients receive PEA PO twice daily (BID) for 8 weeks as long as there is not any unacceptable toxicity. ARM III: Patients receive placebo PO QD for 8 weeks. ARM IV: Patients receive placebo PO BID for 8 weeks. After completion of study intervention, patients are followed up at 6 and 12 months.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 88
• Est. completion date: February 28, 2025
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2
• NOTE: Patients with a history of metastatic cancer or an ECOG performance status of 2 must have laboratory (lab) work completed =< 28 days prior to registration
• Pain, numbness, tingling or other symptoms of CIPN of >= 3 months (90 days) duration for which the patient is seeking an intervention
• Neurotoxic chemotherapy must have been completed >= 3 months (90 days) prior to registration and there must be no further planned neurotoxic -chemotherapy for > 2 months after registration Note: The study is limited to those with taxane- and/or platinum-based neuropathy
• Patient must note tingling, numbness or pain symptoms of at least a four out of ten =< 7 days prior to registration.
• Note: On a 0-10 scale where zero was 'no problem' and ten being 'as bad a problem that could be imagined': how much of a problem has numbness, tingling, and/or pain in your fingers and/or toes been in the past week?
• Patient must be able to speak, read and comprehend English
• For women of childbearing potential only, a negative urine or serum pregnancy test done =< 14 days prior to registration is required
• A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
• NOTE: If the urine test cannot be confirmed as negative, a serum pregnancy test will be required
• Life expectancy >= 6 months
• Platelet count > 100,000/mm^3
• NOTE: Patients with a history of metastatic breast cancer or an ECOG performance status of 2 must have this lab completed =< 28 days prior to registration
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• NOTE: Patients with a history of metastatic breast cancer or an ECOG performance status of 2 must have this lab completed =< 28 days prior to registration
• Hemoglobin > 11 g/dL
• NOTE: Patients with a history of metastatic breast cancer or an ECOG performance status of 2 must have this lab completed =< 28 days prior to registration
• Serum transaminase (alanine aminotransferase [ALT] or aspartate aminotransferase [AST]) =< 1.2 x upper limit of normal (ULN)
• NOTE: Patients with a history of metastatic breast cancer or an ECOG performance status of 2 must have these labs completed =< 28 days prior to registration
• Alkaline phosphatase =< 1.2 x ULN
• NOTE: Patients with a history of metastatic breast cancer or an ECOG performance status of 2 must have this lab completed =< 28 days prior to registration
• Serum creatinine =< 1.2 x ULN
• NOTE: Patients with a history of metastatic cancer or an ECOG performance status of 2 must have this lab completed =< 28 days prior to registration
• Able to swallow oral medication
• Provide written informed consent =< 28 days prior to registration

Exclusion Criteria:

• Currently receiving neurotoxic chemotherapy for a second cancer or recurrence of the primary cancer
• Impaired decision-making capacity (such as with a diagnosis of dementia or memory loss)
• Evidence of residual cancer, per routine clinical practice-based parameters
• Comorbid conditions:
• Previous diagnosis of diabetic or another non chemotherapy induced peripheral neuropathy
• Previous history of peripheral neuropathy prior to receiving neurotoxic chemotherapy
• Neuropathy from human immunodeficiency virus (HIV) infection. Note: Patients with HIV infections are eligible as long as they do not have a neuropathy from their viral illness
• Concurrent use of a cannabis product (tetrahydrocannabinol [THC] and/or cannabidiol [CBD]). Patients should have discontinued these products >= 4 weeks prior to registration
• Current or previous use of PEA
• Currently receiving or planning to start any of the following agents: opioids, duloxetine, gabapentin or pregabalin. Patients are eligible if they discontinue these medications >= 1 week prior to registration
• Any of the following because the 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

Related Conditions & MeSH terms

• Chemotherapy-Induced Peripheral Neuropathy
• Hematopoietic and Lymphoid Cell Neoplasm
• Malignant Solid Neoplasm
• Neoplasms
• Peripheral Nervous System Diseases

Intervention

Drug:
• Palmidrol
Given PEA PO
• Placebo Administration
Given PO

Other:
• Quality-of-Life Assessment
Ancillary studies

Locations

Country	Name	City	State
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Mayo Clinic Health System Eau Claire Hospital-Luther Campus	Eau Claire	Wisconsin
United States	Cone Health Cancer Center	Greensboro	North Carolina
United States	Mayo Clinic Health System-Franciscan Healthcare	La Crosse	Wisconsin
United States	Middlesex Hospital	Middletown	Connecticut
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Mayo Clinic	Rochester	Minnesota
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Carle Cancer Center NCI Community Oncology Research Program	Urbana	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Academic and Community Cancer Research United	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in the two cognitive items of the Cognitive Functioning Assessment	Will be summarized by mean (SD) and median (range) by treatment arm and the combined placebo arm. The difference in change score will be estimated along with the 95% confidence interval.	Baseline up to 8 weeks
Other	Weekly CIPN20 scores	Will be summarized at each time point by mean (SD) and median (range) and will be plotted longitudinally by treatment arm and the combine placebo arm.	Baseline up to 8 weeks
Other	Weekly pain scores	Will be summarized at each time point by mean (SD) and median (range) and will be plotted longitudinally by treatment arm and the combine placebo arm.	Baseline up to 8 weeks
Other	Items of the Global Impression of Change tool	Will be summarized by frequency (percentage) of each level at each time point for each treatment arm and the combine placebo arm. Bar plots for each PEA arm and the combined placebo arm of frequency over time will be constructed.	Baseline up to 8 weeks
Other	Chemotherapy Induced Peripheral Neuropathy Assessment Tool	Will be summarized by mean (SD) and median (range) at each time point for each treatment arm and the combine placebo arm.	Baseline up to 8 weeks
Other	CIPN20 score	Will be calculated for each patient. The mean and standard deviation of the change will be calculated for each PEA arm. The difference in CIPN20 change scores between the two PEA dosage arms will be estimated along with a 95% confidence interval.	Baseline up to 8 weeks
Other	Disease recurrence	The number of events and percentage will be reported by each PEA arm and combined placebo arm. No hypothesis test will be performed between arms.	At 6 and 12 months
Other	Overall survival (OS)	For each PEA arm and combined placebo arm, the distributions of OS time will be estimated using the Kaplan-Meier method. Log-rank test will be used to compare the survival distributions between each PEA and the combined placebo arm.	From registration to death due to any cause, assessed up to 12 months
Primary	Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) score	Will be scored and summarized at each time point for each patient. The change from baseline to 8 weeks will then be calculated for each patient. The mean (standard deviation [SD]) and median (range) of the change will be calculated for each PEA arm and the combined placebo arm. The difference in change scores between each PEA arm and the combined placebo will be estimated along with a 95% confidence interval. For the primary analysis, the CIPN20 analysis dataset will include all eligible patients who are randomized, initiated treatment, and completed the baseline questionnaire. For patients who go off protocol treatment before 8 weeks, the score at their final observation will be used to calculate the change. For patients who do not have any post baseline data, they will be considered to have no change from baseline.	Baseline up to 8 weeks
Secondary	Incidence of adverse events	Adverse events by patient will be summarized by frequencies and severity using Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. The proportion of patients who experience at least one grade 3+ adverse event (regardless of attribution) will be reported. The overall adverse event rates for grade 3 or higher adverse events will be compared across the three arms (the two PEA arms and combined placebo) using a Chi-squared or Fisher's Exact tests as appropriate.	Up to 8 weeks
Secondary	Difference in change of quality of life	Will be assessed by Question 3, patient-reported outcomes-quality of life (PRO-QOL). The mean and standard deviation of the change will be reported for each PEA arm and the combined placebo arm. Additional analysis using data collected from the Symptom Experience Diary may be performed. For patients who go off protocol treatment before 8 weeks, the question 3 response at their final observation will be used to calculate the change. For patients who do not have any post baseline data, they will be considered to have no change from baseline.	Baseline up to 8 weeks