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PEA for the Relief of Chemotherapy-Induced Peripheral Neuropathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05246670
Recruitment Status : Recruiting
First Posted : February 18, 2022
Last Update Posted : November 24, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Academic and Community Cancer Research United

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.

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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

Resource links provided by the National Library of Medicine


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




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.



Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05246670


Locations
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United States, Connecticut
Middlesex Hospital Recruiting
Middletown, Connecticut, United States, 06457
Contact: Robert J. Levy       robert.levy@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 Withdrawn
Rochester, Minnesota, United States, 55905
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 Not yet recruiting
Sioux Falls, South Dakota, United States, 57104
Contact: Tammy Fischer    701-323-5365    tamara.fischer@sanfordhealth.org   
Principal Investigator: Amit Waman Panwalkar         
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 Not yet 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
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Principal Investigator: Mellar P Davis Academic and Community Cancer Research United
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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    Key Record Dates
Last Update Posted: November 24, 2022
Last Verified: September 2022

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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:
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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