Chemotherapy-Induced Peripheral Neuropathy, Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm
Conditions
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.
Interventions
DRUGPalmidrol
Given PEA PO
DRUGPlacebo Administration
Given PO
OTHERQuality-of-Life Assessment
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Academic and Community Cancer Research United
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Items of the Global Impression of Change Tool | Baseline up to 8 weeks | 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. |
| Chemotherapy Induced Peripheral Neuropathy Assessment Tool | Baseline up to 8 weeks | Will be summarized by mean (SD) and median (range) at each time point for each treatment arm and the combine placebo arm. |
| Change in the Two Cognitive Items of the Cognitive Functioning Assessment | Baseline up to 8 weeks | 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. |
| Disease Recurrence | 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. |
| Overall Survival (OS) | 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. |
| CIPN20 Score | 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. |
| Weekly CIPN20 Scores | Baseline up to 8 weeks | 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. |
| Weekly Pain Scores | Baseline up to 8 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lower-dose PEA Patients receive PEA PO QD for 8 weeks as long as there is not any unacceptable toxicity.\> \> Palmidrol: Given PEA PO\>
\> Quality-of-Life Assessment: Ancillary studies | 29 |
| Higher-dose PEA Patients receive PEA PO BID for 8 weeks as long as there is not any unacceptable toxicity.\> \> Palmidrol: Given PEA PO\>
\> Quality-of-Life Assessment: Ancillary studies | 30 |
| QD Placebo Patients receive placebo PO QD for 8 weeks.\> \> Placebo Administration: Given PO\>
\> Quality-of-Life Assessment: Ancillary studies | 14 |
| BID Placebo Patients receive placebo PO BID for 8 weeks.\> \> Placebo Administration: Given PO\>
\> Quality-of-Life Assessment: Ancillary studies | 15 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 | 0 | 1 |
Baseline characteristics
| Characteristic | Lower-dose PEA | Total | BID Placebo | QD Placebo | Higher-dose PEA |
|---|---|---|---|---|---|
| Age, Continuous | 66 years STANDARD_DEVIATION 7.96 | 62.7 years STANDARD_DEVIATION 9.3 | 67.3 years STANDARD_DEVIATION 6.05 | 56.9 years STANDARD_DEVIATION 8.47 | 60 years STANDARD_DEVIATION 10.11 |
| BMI | 32.1 kg/m^2 STANDARD_DEVIATION 8.62 | 32.1 kg/m^2 STANDARD_DEVIATION 7.9 | 31.0 kg/m^2 STANDARD_DEVIATION 7.78 | 35.1 kg/m^2 STANDARD_DEVIATION 8.74 | 31.3 kg/m^2 STANDARD_DEVIATION 6.81 |
| ECOG Performance Status 0 | 14 Participants | 43 Participants | 7 Participants | 8 Participants | 14 Participants |
| ECOG Performance Status 1+ | 15 Participants | 45 Participants | 8 Participants | 6 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 0 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 81 Participants | 15 Participants | 12 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 2 Participants |
| Prior Chemotherapy Any Taxane +/- carboplatin +/- other agents | 21 Participants | 63 Participants | 11 Participants | 10 Participants | 21 Participants |
| Prior Chemotherapy Other (never received a taxane nor oxaliplatin) | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Prior Chemotherapy Oxaliplatin based | 8 Participants | 24 Participants | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 13 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 22 Participants | 72 Participants | 13 Participants | 12 Participants | 25 Participants |
| Region of Enrollment United States | 29 participants | 88 participants | 15 participants | 14 participants | 30 participants |
| Sex: Female, Male Female | 24 Participants | 71 Participants | 12 Participants | 11 Participants | 24 Participants |
| Sex: Female, Male Male | 5 Participants | 17 Participants | 3 Participants | 3 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 30 | 0 / 14 | 0 / 15 |
| other Total, other adverse events | 8 / 29 | 6 / 30 | 3 / 14 | 3 / 15 |
| serious Total, serious adverse events | 2 / 29 | 0 / 30 | 2 / 14 | 0 / 15 |
Outcome results
Primary
Mean Change in 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, 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.
Time frame: 8 weeks
Population: All evaluable participants were included in analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lower-dose PEA | Mean Change in Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) Score | -4.2 units on a scale | Standard Deviation 5.42 |
| Higher-dose PEA | Mean Change in Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) Score | -6.3 units on a scale | Standard Deviation 12.24 |
| Combined Placebo | Mean Change in Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) Score | -6.4 units on a scale | Standard Deviation 7.5 |
95% CI: [-1.33, 5.74]
95% CI: [-5.23, 5.41]
95% CI: [-2.87, 7.09]
Secondary
Mean 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. 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.
Time frame: 8 weeks
Population: All evaluable participants were included in analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lower-dose PEA | Mean Change of Quality of Life | 0.6 units on a scale | Standard Deviation 2.71 |
| Higher-dose PEA | Mean Change of Quality of Life | 0.6 units on a scale | Standard Deviation 2.73 |
| Combined Placebo | Mean Change of Quality of Life | -0.6 units on a scale | Standard Deviation 1.91 |
Secondary
Number of Participants Experiencing Grade 3+ 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).
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lower-dose PEA | Number of Participants Experiencing Grade 3+ Adverse Events | 2 Participants |
| Higher-dose PEA | Number of Participants Experiencing Grade 3+ Adverse Events | 0 Participants |
| Combined Placebo | Number of Participants Experiencing Grade 3+ Adverse Events | 2 Participants |
Other Pre-specified
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.
Time frame: Baseline up to 8 weeks
Other Pre-specified
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.
Time frame: Baseline up to 8 weeks
Other Pre-specified
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.
Time frame: Baseline up to 8 weeks
Other Pre-specified
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.
Time frame: At 6 and 12 months
Other Pre-specified
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.
Time frame: Baseline up to 8 weeks
Other Pre-specified
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.
Time frame: From registration to death due to any cause, assessed up to 12 months
Other Pre-specified
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.
Time frame: Baseline up to 8 weeks
Other Pre-specified
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.
Time frame: Baseline up to 8 weeks