Clinical trial NCT05246670: PEA for the Relief of Chemotherapy-Induced Peripheral Neuropathy
Official title: Treatment of Established Chemotherapy-Induced Neuropathy With N-Palmitoylethanolamide, a Cannabimimetic Nutraceutical: A Randomized Double-Blind Phase II Pilot Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Chemotherapy-Induced Peripheral Neuropathy
Hematopoietic and Lymphoid Cell Neoplasm
Malignant Solid Neoplasm
Lead sponsor: Academic and Community Cancer Research United
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2022-02-18
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Change in Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) Score
timeFrame: 8 weeks
Secondary outcomes:
measure: Number of Participants Experiencing Grade 3+ Adverse Events
timeFrame: 8 weeks
measure: Mean Change of Quality of Life
timeFrame: 8 weeks
Other outcomes:
measure: Change in the Two Cognitive Items of the Cognitive Functioning Assessment
timeFrame: Baseline up to 8 weeks
measure: Weekly CIPN20 Scores
timeFrame: Baseline up to 8 weeks
measure: Weekly Pain Scores
timeFrame: Baseline up to 8 weeks
measure: Items of the Global Impression of Change Tool
timeFrame: Baseline up to 8 weeks
measure: Chemotherapy Induced Peripheral Neuropathy Assessment Tool
timeFrame: Baseline up to 8 weeks
measure: CIPN20 Score
timeFrame: Baseline up to 8 weeks
measure: Disease Recurrence
timeFrame: At 6 and 12 months
measure: Overall Survival (OS)
timeFrame: From registration to death due to any cause, assessed up to 12 months
Locations:
city: Middletown
country: United States
facility: Middlesex Hospital
state: Connecticut
city: Urbana
country: United States
facility: Carle Cancer Center NCI Community Oncology Research Program
state: Illinois
city: Sioux City
country: United States
facility: Siouxland Regional Cancer Center
state: Iowa
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Greensboro
country: United States
facility: Cone Health Cancer Center
state: North Carolina
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Eau Claire
country: United States
facility: Mayo Clinic Health System Eau Claire Hospital-Luther Campus
state: Wisconsin
city: La Crosse
country: United States
facility: Mayo Clinic Health System-Franciscan Healthcare
state: Wisconsin
Study officials:
affiliation: Academic and Community Cancer Research United
name: Mellar P Davis
role: PRINCIPAL_INVESTIGATOR
References: