PEA for the Relief of Chemotherapy-Induced Peripheral Neuropathy

Phase 2

Active, not recruiting

Conditions: Chemotherapy-Induced Peripheral Neuropathy
Hematopoietic and Lymphoid Cell Neoplasm
Malignant Solid Neoplasm

Interventions: Drug: Placebo Administration
Drug: Palmidrol
Other: Quality-of-Life Assessment

Registration Number: NCT05246670

Lead Sponsor: 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.

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 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 & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 88

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BID placebo	Placebo Administration	Patients receive placebo PO BID for 8 weeks.
BID placebo	Quality-of-Life Assessment	Patients receive placebo PO BID for 8 weeks.
Higher-dose PEA	Palmidrol	Patients receive PEA PO BID for 8 weeks as long as there is not any unacceptable toxicity.
Higher-dose PEA	Quality-of-Life Assessment	Patients receive PEA PO BID for 8 weeks as long as there is not any unacceptable toxicity.
Lower-dose PEA	Palmidrol	Patients receive PEA PO QD for 8 weeks as long as there is not any unacceptable toxicity.
Lower-dose PEA	Quality-of-Life Assessment	Patients receive PEA PO QD for 8 weeks as long as there is not any unacceptable toxicity.
QD placebo	Placebo Administration	Patients receive placebo PO QD for 8 weeks.
QD placebo	Quality-of-Life Assessment	Patients receive placebo PO QD for 8 weeks.

Primary Outcome Measures

Name	Time	Method
Mean Change in Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) Score	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, 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. The CIPN20 includes 20 items, each asking a participant to rate their experience with certain symptoms from 1 to 4, with 1 being no difficulty with the symptom and 4 being the most difficulty with the symptom. Answers are then summed to give a total score from 20 to 80.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Experiencing Grade 3+ Adverse Events	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).
Mean Change of Quality of Life	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. 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. Question 3 of the PRO-QOL is a 10 point scale asking participants to rate their quality of life, with 0 being the worst and 10 being the best.

Trial Locations

Locations (10): Mayo Clinic Health System-Franciscan Healthcare
🇺🇸
La Crosse, Wisconsin, United States
Siouxland Regional Cancer Center
🇺🇸
Sioux City, Iowa, United States
Cone Health Cancer Center
🇺🇸
Greensboro, North Carolina, United States
Middlesex Hospital
🇺🇸
Middletown, Connecticut, United States
Rapid City Regional Hospital
🇺🇸
Rapid City, South Dakota, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Mayo Clinic Health System Eau Claire Hospital-Luther Campus
🇺🇸
Eau Claire, Wisconsin, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Carle Cancer Center NCI Community Oncology Research Program
🇺🇸
Urbana, Illinois, United States