PEA for the Relief of Chemotherapy-Induced Peripheral Neuropathy

• ClinicalTrials.gov Identifier: NCT05246670
• Recruitment Status: Recruiting
• First Posted: February 18, 2022
• Last Update Posted: March 10, 2023
• Sponsor: Academic and Community Cancer Research United
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Academic and Community Cancer Research United

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Chemotherapy-Induced Peripheral Neuropathy; Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm	Drug: Palmidrol; Drug: Placebo Administration; Other: Quality-of-Life Assessment	Phase 2

Detailed 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 symptoms and quality of life from baseline to the end of 8 weeks.

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 88 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Treatment of Established Chemotherapy-Induced Neuropathy With N-Palmitoylethanolamide, a Cannabimimetic Nutraceutical: A Randomized Double-Blind Phase II Pilot Trial
• Actual Study Start Date: May 16, 2022
• Estimated Primary Completion Date: August 31, 2023
• Estimated Study Completion Date: June 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm I (lower-dose PEA); Patients receive PEA PO QD for 8 weeks as long as there is not any unacceptable toxicity.	Drug: Palmidrol; Given PEA PO; Other Names: N-Palmitoyl Ethanolamide; N-Palmitoylethanolamide; OptiPEA; Palmitoyl Ethanolamide; Palmitoylethanolamide; PEA; Other: Quality-of-Life Assessment; Ancillary studies; Other Name: Quality of Life Assessment
Experimental: Arm II (higher-dose PEA); Patients receive PEA PO BID for 8 weeks as long as there is not any unacceptable toxicity.	Drug: Palmidrol; Given PEA PO; Other Names: N-Palmitoyl Ethanolamide; N-Palmitoylethanolamide; OptiPEA; Palmitoyl Ethanolamide; Palmitoylethanolamide; PEA; Other: Quality-of-Life Assessment; Ancillary studies; Other Name: Quality of Life Assessment
Placebo Comparator: Arm III (QD placebo); Patients receive placebo PO QD for 8 weeks.	Drug: Placebo Administration; Given PO; Other: Quality-of-Life Assessment; Ancillary studies; Other Name: Quality of Life Assessment
Placebo Comparator: Arm IV (BID placebo); Patients receive placebo PO BID for 8 weeks.	Drug: Placebo Administration; Given PO; Other: Quality-of-Life Assessment; Ancillary studies; Other Name: Quality of Life Assessment

Outcome Measures

Primary Outcome Measures :

1. Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) score [ Time Frame: Baseline up to 8 weeks ]
   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.

Secondary Outcome Measures :

1. Incidence of adverse events [ Time Frame: Up to 8 weeks ]
   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.
2. Difference in change of quality of life [ Time Frame: Baseline up to 8 weeks ]
   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. 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.

Other Outcome Measures:

1. Change in the two cognitive items of the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline up to 8 weeks ]
   Will be summarized by mean (SD) and median (range) by treatment arm. The difference in change score will be estimated along with the 95% confidence interval.
2. Weekly CIPN20 scores [ Time Frame: Baseline up to 8 weeks ]
   Will be summarized at each time point by mean (SD) and median (range) by treatment arm and will be plotted longitudinally.
3. Weekly pain scores [ Time Frame: Baseline up to 8 weeks ]
   Will be summarized at each time point by mean (SD) and median (range) by treatment arm and will be plotted longitudinally.
4. Items of the Global Impression of Change tool [ Time Frame: Baseline up to 8 weeks ]
   Will be summarized by frequency (percentage) of each level at each time point for each treatment arm. Bar plots of impression of change by treatment arm over time will be constructed.
5. Chemotherapy Induced Peripheral Neuropathy Assessment Tool [ Time Frame: Baseline up to 8 weeks ]
   Will be summarized by mean (SD) and median (range) at each time point for each treatment arm.
6. CIPN20 score [ Time Frame: Baseline up to 8 weeks ]
   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.
7. Disease recurrence [ Time Frame: At 6 and 12 months ]
   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.
8. Overall survival (OS) [ Time Frame: From registration to death due to any cause, assessed up to 12 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age >= 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, 2

  • NOTE: Patients with a history of metastatic breast 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 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 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 breast 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 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

Contacts and Locations

Locations

United States, Connecticut

Middlesex Hospital; Recruiting

Middletown, Connecticut, United States, 06457

Contact: Loriann MacLean 860-358-2015 Loriann.maclean@midhosp.org

Principal Investigator: Robert J. Levy

United States, Illinois

Illinois CancerCare-Peoria; Withdrawn

Peoria, Illinois, United States, 61615

Carle Cancer Center NCI Community Oncology Research Program; Recruiting

Urbana, Illinois, United States, 61801

Contact: Shelly McCaskill 217-383-3512 Shelly.mccskill@carle.com

Principal Investigator: Vamsi K. Vasireddy, DO

United States, Iowa

Siouxland Regional Cancer Center; Recruiting

Sioux City, Iowa, United States, 51101

Contact: Tom Hoopingarner, RN,BSN,CCRP 712-252-9326 hoopingarnert@JENCC.com

Principal Investigator: Donald B. Wender

United States, Minnesota

Mayo Clinic; Not yet recruiting

Rochester, Minnesota, United States, 55905

Contact: Charles L. Loprinzi cloprinzi@mayo.edu

Principal Investigator: Charles L. Loprinzi

United States, North Carolina

Cone Health Cancer Center; Recruiting

Greensboro, North Carolina, United States, 27403

Contact: Stacey Phelps 336-832-0836 stacey.phelps@conehealth.com

Principal Investigator: Vinay K. Gudena, MD MPH

United States, Ohio

Columbus NCI Community Oncology Research Program; Withdrawn

Columbus, Ohio, United States, 43215

United States, Pennsylvania

Geisinger Medical Center; Not yet recruiting

Danville, Pennsylvania, United States, 17822

Contact: John Seeley 570-214-2725 jpseeley@geisinger.edu

Principal Investigator: Mellar Davis

United States, South Dakota

Monument Health Rapid City Hospital; Recruiting

Rapid City, South Dakota, United States, 57701

Contact: Angie Dunbar, RN 605-755-2370 adunbar@monument.health

Principal Investigator: Abdel-Ghani Azzouqa, M.D.

Sanford NCI Community Oncology Research Program of the North Central Plains; Withdrawn

Sioux Falls, South Dakota, United States, 57104

United States, Tennessee

Vanderbilt University/Ingram Cancer Center; Not yet recruiting

Nashville, Tennessee, United States, 37203

Contact: Rajiv Agarwal, M.D. 615-936-8422 rajiv.agarwal@vumc.org

Principal Investigator: Rajiv Agarwal, M.D.

United States, Wisconsin

Mayo Clinic Health System Eau Claire Hospital-Luther Campus; Recruiting

Eau Claire, Wisconsin, United States, 54703

Contact: Rebecca Schmidt 715-828-5137 Schmidt.Rebecca2@mayo.edu

Principal Investigator: Eyad Al-Hattab

Mayo Clinic Health System-Franciscan Healthcare; Recruiting

La Crosse, Wisconsin, United States, 54601

Contact: Jonathan Ticku ticku.jonathan@mayo.edu

Principal Investigator: Jonathan Ticku

Sponsors and Collaborators

Academic and Community Cancer Research United

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Mellar P Davis; Academic and Community Cancer Research United

More Information

• Responsible Party: Academic and Community Cancer Research United
• ClinicalTrials.gov Identifier: NCT05246670
• Other Study ID Numbers: ACCRU-SC-2102; NCI-2022-00002 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); ACCRU-SC-2102 ( Other Identifier: Academic and Community Cancer Research United ); P30CA015083 ( U.S. NIH Grant/Contract )
• First Posted: February 18, 2022
• Last Update Posted: March 10, 2023
• Last Verified: September 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Neoplasms; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Palmidrol; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antiviral Agents; Anti-Infective Agents; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists