Chemotherapy-Induced Peripheral Neuropathy, Malignant Solid Neoplasm
Conditions
Brief summary
This clinical trial compares topical cannabidiol to placebo in improving chemotherapy-induced peripheral neuropathy, or painful sensations in your hands or feet due to chemotherapy. Peripheral neuropathy is a nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in different parts of the body. It usually begins in the hands or feet and gets worse over time. Peripheral neuropathy caused by chemotherapy is called chemotherapy-induced peripheral neuropathy (CIPN). CIPN is commonly seen in patients receiving certain chemotherapy medications and is hard to treat. Medications commonly used to treat CIPN have limited benefits and may cause significant side effects. A small report showed that topical cannabidiol may help treat neuropathy in patients with diabetes. This study is being done to determine if cannabidiol cream can help improve the symptoms of CIPN.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate whether topical cannabidiol (CBD) improves CIPN, compared to placebo. II. To evaluate side effects from topical CBD cream use, compared to placebo. SECONDARY OBJECTIVES: I. Other measures of neuropathy as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) CIPN20 motor subscale, the EORTC QLQ CIPN20 autonomic scale, and the total Common Terminology Criteria for Adverse Events (CTCAE) neuropathy scale. II. Adverse event profiles will also be assessed using symptom questionnaires and CTCAE version (v)5.0. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients apply cannabidiol cream topically to affected areas twice daily (BID) for 14 days. Patients then apply placebo cream topically to affected areas BID for 14 days. ARM II: Patients apply placebo cream topically to affected areas BID for 14 days. Patients then apply cannabidiol cream topically to affected areas BID for 14 days.
Interventions
DRUGCannabidiol
Applied topically
DRUGPlacebo Administration
Applied topically
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>= 18 years * English speaking * Cancer diagnosis of any tumor type with chemotherapy-induced neuropathy * At least 4 out of 10 severity of neuropathy pain and/or tingling * Stable for at least 7 days prior to registration on medications for neuropathy, if any are being used * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 * Negative pregnancy test done =\< 7 days prior to registration, for persons of childbearing potential only * NOTE: If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Able to provide written informed consent * Ability to complete questionnaire(s) by themselves or with assistance * No evidence of residual cancer * Platelet count \> 100,000/mm\^3 (following completion of chemotherapy) * Absolute neutrophil count (ANC) \>= 1,000/mm\^3 (following completion of chemotherapy) * Hemoglobin \> 11 g/dL (following completion of chemotherapy) * Serum transaminase (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\]) =\< 1.2 x upper limit of normal (ULN) (following completion of chemotherapy) * Alkaline phosphatase =\< 1.2 x ULN (following completion of chemotherapy) * Serum creatinine =\< 1.2 x ULN (following completion of chemotherapy)
Exclusion criteria
* Any of the following because this 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 * Any medical condition that would prohibit use of a topical cream (skin infection or open wound in the area of the neuropathy) * Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens * Pre-existing neuropathy prior to chemotherapy that would confuse the issue of CIPN * Currently on chemotherapy or received chemotherapy treatment within the prior 3 months * Use of other cannabis products within 30 days prior to registration * History of allergy to cannabis products
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Chemotherapy-induced Peripheral Neuropathy (CIPN) From Baseline | Week 1, week 2, week 3, and week 4 | CIPN will be measured by the sensory subscale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-CIPN20 which is composed of 9 individual items. Each item is scored on a 1-to-4 scale, where 1 means not at all and 4 means very much. Higher scores indicate greater severity of symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in EORTC QLQ CIPN20 Motor Subscale From Baseline | Week 1, week 2, week 3, and week 4 | Motor symptoms of CIPN will be measured by the motor subscale of the EEORTC QLQ-CIPN20 which is composed of 8 individual items. Each item is scored on a 1-to-4 scale, where 1 means not at all and 4 means very much. Higher scores indicate greater severity of symptoms. Will be compared between arms using two-sample, two-sided t-tests. The cannabidiol arm will be compared to the placebo arm. Will construct 95% confidence intervals for the mean difference in sensory neuropathy score between arms. Repeated measures mixed models will be applied to the sensory scores over all time points to determine longitudinal effects and to adjust for confounding factors. Graphical results will include profile plots over time, stream plots of individual changes over time, and forest plots of the 95% confidence intervals by arm. |
| Change in EORTC QLQ CIPN20 Autonomic Scale From Baseline | Week 1, week 2, week 3, and week 4 | Autonomic nervous system symptoms related to CIPN will be measured by the autonomic subscale of the EEORTC QLQ-CIPN20 which is composed of 3 individual items answered on a 4-point scale ranging from not at all' to very much. . Higher scores indicate more severe symptoms. Will be compared between arms using two-sample, two-sided t-tests. The cannabidiol arm will be compared to the placebo arm. Will construct 95% confidence intervals for the mean difference in sensory neuropathy score between arms. Repeated measures mixed models will be applied to the sensory scores over all time points to determine longitudinal effects and to adjust for confounding factors. Graphical results will include profile plots over time, stream plots of individual changes over time, and forest plots of the 95% confidence intervals by arm. |
| Incidence of Adverse Events (AEs) | Up to 14 days for each part of a sequence | Incidence of AEs will be reported per arm, assessed using Common Terminology Criteria (CTCAE) version 5.0. |
| Incidence of Grade 3 or Higher Adverse Events | Up to 28 days | Will be assessed using symptom questionnaires and CTCAE version 5.0. Will compare the maximum (worst) values between arms. Fisher's exact tests will be used to compare incidence rates and Wilcoxon rank-sum tests will be used to compare maximum values between arms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Cannabidiol, Placebo) Patients apply cannabidiol cream topically to affected areas BID for 14 days. Patients then apply placebo cream topically to affected areas BID for 14 days.\> \> Cannabidiol: Applied topically\>
\> Placebo Administration: Applied topically\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> Questionnaire Administration: Ancillary studies | 20 |
| Arm II (Placebo, Cannabidiol) Patients apply placebo cream topically to affected areas BID for 14 days. Patients then apply cannabidiol cream topically to affected areas BID for 14 days.\> \> Cannabidiol: Applied topically\>
\> Placebo Administration: Applied topically\>
\> Quality-of-Life Assessment: Ancillary studies\>
\> Questionnaire Administration: Ancillary studies | 18 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Initial Treatment | Ineligible | 0 | 1 |
| Initial Treatment | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Arm I (Cannabidiol, Placebo) | Arm II (Placebo, Cannabidiol) | Total |
|---|---|---|---|
| Age, Continuous | 64.3 years STANDARD_DEVIATION 12.3 | 61.3 years STANDARD_DEVIATION 10.3 | 62.9 years STANDARD_DEVIATION 11.3 |
| Any Prior Cancer Therapy | 20 Participants | 18 Participants | 38 Participants |
| ECOG Performance Status 0 | 15 Participants | 14 Participants | 29 Participants |
| ECOG Performance Status 1 | 5 Participants | 2 Participants | 7 Participants |
| ECOG Performance Status 2 | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 18 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Height (cm) | 169.1 cm STANDARD_DEVIATION 8.6 | 170.8 cm STANDARD_DEVIATION 8.6 | 169.9 cm STANDARD_DEVIATION 8.5 |
| NCI-CTCAE v5.0 CIPN Grade I | 1 Participants | 1 Participants | 2 Participants |
| NCI-CTCAE v5.0 CIPN Grade II | 11 Participants | 11 Participants | 22 Participants |
| NCI-CTCAE v5.0 CIPN Grade III | 3 Participants | 5 Participants | 8 Participants |
| NCI-CTCAE v5.0 CIPN Grade IV | 5 Participants | 0 Participants | 5 Participants |
| NCI-CTCAE v5.0 CIPN Grade Missing | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 17 Participants | 16 Participants | 33 Participants |
| Sex: Female, Male Female | 13 Participants | 12 Participants | 25 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 13 Participants |
| Weight (Kg) | 87.4 Kg STANDARD_DEVIATION 17.1 | 85.4 Kg STANDARD_DEVIATION 14.8 | 86.5 Kg STANDARD_DEVIATION 15.9 |
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 / 20 | 0 / 20 | 0 / 19 | 0 / 17 |
| other Total, other adverse events | 2 / 20 | 0 / 20 | 0 / 19 | 0 / 17 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 19 | 0 / 17 |
Outcome results
Primary
Change in Chemotherapy-induced Peripheral Neuropathy (CIPN) From Baseline
CIPN will be measured by the sensory subscale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-CIPN20 which is composed of 9 individual items. Each item is scored on a 1-to-4 scale, where 1 means not at all and 4 means very much. Higher scores indicate greater severity of symptoms.
Time frame: Week 1, week 2, week 3, and week 4
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm I (Cannabidiol, Placebo) | Change in Chemotherapy-induced Peripheral Neuropathy (CIPN) From Baseline | Week 1 | 147.95 percentage of change in CIPN |
| Arm I (Cannabidiol, Placebo) | Change in Chemotherapy-induced Peripheral Neuropathy (CIPN) From Baseline | Week 3 | 148.83 percentage of change in CIPN |
| Arm I (Cannabidiol, Placebo) | Change in Chemotherapy-induced Peripheral Neuropathy (CIPN) From Baseline | Week 4 | 181.39 percentage of change in CIPN |
| Arm I (Cannabidiol, Placebo) | Change in Chemotherapy-induced Peripheral Neuropathy (CIPN) From Baseline | Week 2 | 167.96 percentage of change in CIPN |
| Arm II (Placebo, Cannabidiol) | Change in Chemotherapy-induced Peripheral Neuropathy (CIPN) From Baseline | Week 4 | 142.72 percentage of change in CIPN |
| Arm II (Placebo, Cannabidiol) | Change in Chemotherapy-induced Peripheral Neuropathy (CIPN) From Baseline | Week 1 | 135.82 percentage of change in CIPN |
| Arm II (Placebo, Cannabidiol) | Change in Chemotherapy-induced Peripheral Neuropathy (CIPN) From Baseline | Week 2 | 148.45 percentage of change in CIPN |
| Arm II (Placebo, Cannabidiol) | Change in Chemotherapy-induced Peripheral Neuropathy (CIPN) From Baseline | Week 3 | 140.33 percentage of change in CIPN |
Secondary
Change in EORTC QLQ CIPN20 Autonomic Scale From Baseline
Autonomic nervous system symptoms related to CIPN will be measured by the autonomic subscale of the EEORTC QLQ-CIPN20 which is composed of 3 individual items answered on a 4-point scale ranging from not at all' to very much. . Higher scores indicate more severe symptoms. Will be compared between arms using two-sample, two-sided t-tests. The cannabidiol arm will be compared to the placebo arm. Will construct 95% confidence intervals for the mean difference in sensory neuropathy score between arms. Repeated measures mixed models will be applied to the sensory scores over all time points to determine longitudinal effects and to adjust for confounding factors. Graphical results will include profile plots over time, stream plots of individual changes over time, and forest plots of the 95% confidence intervals by arm.
Time frame: Week 1, week 2, week 3, and week 4
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm I (Cannabidiol, Placebo) | Change in EORTC QLQ CIPN20 Autonomic Scale From Baseline | Week 1 | 110.88 percentage of change in EORTC |
| Arm I (Cannabidiol, Placebo) | Change in EORTC QLQ CIPN20 Autonomic Scale From Baseline | Week 2 | 123.91 percentage of change in EORTC |
| Arm I (Cannabidiol, Placebo) | Change in EORTC QLQ CIPN20 Autonomic Scale From Baseline | Week 3 | 112.07 percentage of change in EORTC |
| Arm I (Cannabidiol, Placebo) | Change in EORTC QLQ CIPN20 Autonomic Scale From Baseline | Week 4 | 120.71 percentage of change in EORTC |
| Arm II (Placebo, Cannabidiol) | Change in EORTC QLQ CIPN20 Autonomic Scale From Baseline | Week 4 | 104.34 percentage of change in EORTC |
| Arm II (Placebo, Cannabidiol) | Change in EORTC QLQ CIPN20 Autonomic Scale From Baseline | Week 1 | 99.59 percentage of change in EORTC |
| Arm II (Placebo, Cannabidiol) | Change in EORTC QLQ CIPN20 Autonomic Scale From Baseline | Week 3 | 100.55 percentage of change in EORTC |
| Arm II (Placebo, Cannabidiol) | Change in EORTC QLQ CIPN20 Autonomic Scale From Baseline | Week 2 | 100.85 percentage of change in EORTC |
Secondary
Change in EORTC QLQ CIPN20 Motor Subscale From Baseline
Motor symptoms of CIPN will be measured by the motor subscale of the EEORTC QLQ-CIPN20 which is composed of 8 individual items. Each item is scored on a 1-to-4 scale, where 1 means not at all and 4 means very much. Higher scores indicate greater severity of symptoms. Will be compared between arms using two-sample, two-sided t-tests. The cannabidiol arm will be compared to the placebo arm. Will construct 95% confidence intervals for the mean difference in sensory neuropathy score between arms. Repeated measures mixed models will be applied to the sensory scores over all time points to determine longitudinal effects and to adjust for confounding factors. Graphical results will include profile plots over time, stream plots of individual changes over time, and forest plots of the 95% confidence intervals by arm.
Time frame: Week 1, week 2, week 3, and week 4
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm I (Cannabidiol, Placebo) | Change in EORTC QLQ CIPN20 Motor Subscale From Baseline | Week 1 | 129.79 percentage of change in EORTC |
| Arm I (Cannabidiol, Placebo) | Change in EORTC QLQ CIPN20 Motor Subscale From Baseline | Week 2 | 135.63 percentage of change in EORTC |
| Arm I (Cannabidiol, Placebo) | Change in EORTC QLQ CIPN20 Motor Subscale From Baseline | Week 3 | 126.09 percentage of change in EORTC |
| Arm I (Cannabidiol, Placebo) | Change in EORTC QLQ CIPN20 Motor Subscale From Baseline | Week 4 | 134.85 percentage of change in EORTC |
| Arm II (Placebo, Cannabidiol) | Change in EORTC QLQ CIPN20 Motor Subscale From Baseline | Week 4 | 123.26 percentage of change in EORTC |
| Arm II (Placebo, Cannabidiol) | Change in EORTC QLQ CIPN20 Motor Subscale From Baseline | Week 1 | 114.11 percentage of change in EORTC |
| Arm II (Placebo, Cannabidiol) | Change in EORTC QLQ CIPN20 Motor Subscale From Baseline | Week 3 | 121.61 percentage of change in EORTC |
| Arm II (Placebo, Cannabidiol) | Change in EORTC QLQ CIPN20 Motor Subscale From Baseline | Week 2 | 131.13 percentage of change in EORTC |
Secondary
Incidence of Adverse Events (AEs)
Incidence of AEs will be reported per arm, assessed using Common Terminology Criteria (CTCAE) version 5.0.
Time frame: Up to 14 days for each part of a sequence
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (Cannabidiol, Placebo) | Incidence of Adverse Events (AEs) | Spinal fracture | 1 Participants |
| Arm I (Cannabidiol, Placebo) | Incidence of Adverse Events (AEs) | Hypotension | 1 Participants |
| Arm I (Cannabidiol, Placebo) | Incidence of Adverse Events (AEs) | Back pain | 1 Participants |
| Arm II (Placebo, Cannabidiol) | Incidence of Adverse Events (AEs) | Spinal fracture | 0 Participants |
| Arm II (Placebo, Cannabidiol) | Incidence of Adverse Events (AEs) | Hypotension | 0 Participants |
| Arm II (Placebo, Cannabidiol) | Incidence of Adverse Events (AEs) | Back pain | 0 Participants |
| Arm I Crossover (Cannabidiol, Placebo) | Incidence of Adverse Events (AEs) | Back pain | 0 Participants |
| Arm I Crossover (Cannabidiol, Placebo) | Incidence of Adverse Events (AEs) | Spinal fracture | 0 Participants |
| Arm I Crossover (Cannabidiol, Placebo) | Incidence of Adverse Events (AEs) | Hypotension | 0 Participants |
| Arm II Crossover (Placebo, Cannabidiol) | Incidence of Adverse Events (AEs) | Spinal fracture | 0 Participants |
| Arm II Crossover (Placebo, Cannabidiol) | Incidence of Adverse Events (AEs) | Hypotension | 0 Participants |
| Arm II Crossover (Placebo, Cannabidiol) | Incidence of Adverse Events (AEs) | Back pain | 0 Participants |
Secondary
Incidence of Grade 3 or Higher Adverse Events
Will be assessed using symptom questionnaires and CTCAE version 5.0. Will compare the maximum (worst) values between arms. Fisher's exact tests will be used to compare incidence rates and Wilcoxon rank-sum tests will be used to compare maximum values between arms.
Time frame: Up to 28 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (Cannabidiol, Placebo) | Incidence of Grade 3 or Higher Adverse Events | Grade 3 | 2 Participants |
| Arm I (Cannabidiol, Placebo) | Incidence of Grade 3 or Higher Adverse Events | Grade 4+ | 0 Participants |
| Arm II (Placebo, Cannabidiol) | Incidence of Grade 3 or Higher Adverse Events | Grade 4+ | 0 Participants |
| Arm II (Placebo, Cannabidiol) | Incidence of Grade 3 or Higher Adverse Events | Grade 3 | 0 Participants |
| Arm I Crossover (Cannabidiol, Placebo) | Incidence of Grade 3 or Higher Adverse Events | Grade 3 | 0 Participants |
| Arm I Crossover (Cannabidiol, Placebo) | Incidence of Grade 3 or Higher Adverse Events | Grade 4+ | 0 Participants |
| Arm II Crossover (Placebo, Cannabidiol) | Incidence of Grade 3 or Higher Adverse Events | Grade 3 | 0 Participants |
| Arm II Crossover (Placebo, Cannabidiol) | Incidence of Grade 3 or Higher Adverse Events | Grade 4+ | 0 Participants |