Phytocannabinoids for the Treatment of Chronic Chemotherapy-Induced Peripheral Neuropathy in Breast and Colon Cancer Survivors

Breast Carcinoma Clinical Trial

Official title:

A Pilot Study to Evaluate the Benefits of Phytocannabinoids for the Treatment of Chronic Chemotherapy-Induced Peripheral Neuropathy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05672342
• Other study ID #: 22339
• Secondary ID: NCI-2022-1025322
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: July 6, 2024
• Est. completion date: October 31, 2025

Study information

• Verified date: March 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial tests how well phytocannabinoids (cannabidiol [CBD] and tetrahydrocannbinol [THC]) work in reducing chronic chemotherapy-induced peripheral neuropathy (CIPN) in breast and colon cancer survivors. Neuropathy is the most common neurological symptom reported by cancer patients due to treatment. A variety of pharmacologic treatments have been evaluated to alleviate CIPN symptoms; however, no definitive treatment has been found to successfully treat all the symptoms of CIPN. Therefore, investigators continue to seek other possible treatment options including cannabis. Phytocannabinoids may be a particularly useful intervention for cancer patients given the limited effective treatments for CIPN. In addition, cannabis-based medicines have become tremendously popular as both cancer patients and clinicians are seeking therapies with fewer potential risks of dependency and other side effects. This trial is being done to provide cancer patients and clinicians with reliable information to help guide their use of phytocannabinoids to manage the tremendous distress and pain experienced by many cancer patients, which impacts their long-term quality of life.

Description:

PRIMARY OBJECTIVE:

I. Assess the ability of CBD and THC:CBD to reduce CIPN symptoms as compared to placebo using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group (FACT/GOG)-Neurotoxicity (Ntx) subscale among breast and colon cancer survivors.

SECONDARY OBJECTIVES:

I. Evaluate the impact of CBD and THC:CBD as compared to placebo on quality of life using the Functional Assessment of Cancer Therapy General (FACT-G) among breast and colon cancer survivors with chronic CIPN.

II. Document the utilization of neuropathic and pain medications by cancer patients with chronic CIPN during treatment with CBD and THC:CBD as compared to placebo.

III. Describe the side effects of CBD and THC:CBD treatment.

EXPLORATORY OBJECTIVES:

I. Assess neurological symptoms and function with the Neuropathy Pain Scale (NPS), Total Neuropathy Sccore - clinically based (TNSc), quantitative sensory testing (QST), Grooved Pegboard Test (GPT), and Unipedal Stance balance test (USBT) among patients with chronic CIPN treated with CBD and THC:CBD as compared to placebo.

II. Evaluate for predictors of response to CBD and THC:CBD for chronic CIPN.

OUTLINE: This is a dose-escalation study of CBD and THC. Patients are randomized to 1 of 3 arms.

ARM I: Patients receive CBD orally (PO) on study.

ARM II: Patients receive CBD PO + THC PO on study.

ARM III: Patients receive placebo PO on study.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: October 31, 2025
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorized representative

• Assent, when appropriate, will be obtained per institutional guidelines

• Agreement to allow the use of archival tissue from diagnostic tumor biopsies

• If unavailable, exceptions may be granted with study principal investigator (PI) approval

• Willingness to comply with all study interventions including the use of medical cannabis and follow-up assessments

• Age: >= 18 years

• Eastern Cooperative Oncology Group (ECOG) =< 2

• Ability to read and understand English for questionnaires

• Patients must have either neuropathy >= 1 according to Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 scale or a neuropathy score of > 3 on a 0-10 scale plus a FACT/GOG-Ntx score of > 10

• The patient's previous chemotherapy treatment must have included a taxane (paclitaxel, nab-paclitaxel, or docetaxel) or platinum (cisplatin, oxaliplatin, or carboplatin) and considered the primary cause of the neuropathy by the medical team

• Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless has Gilbert's disease)

• Aspartate aminotransferase (AST) =< 3 x ULN

• Alanine aminotransferase (ALT) =< 3 x ULN

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 1 months after the last dose of protocol therapy

• Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

• Current active treatment with chemotherapy, radiation or surgery in the past 3 months or planned treatment during this study protocol period. Note: Hormonal therapy is allowed

Exclusion Criteria:

• Concurrent use of other alternative medicines such as medical cannabis, herbal agents and high dose vitamins and minerals

• Liver cirrhosis Child-Pugh B or C

• Mental incapacitation or significant emotional or psychological disorder that, in the opinion of the investigators, precludes study entry (These patients may not be able to cooperate with this slightly invasive procedure or with the data collection process)

• History of diabetic neuropathy, neuropathy related to human immunodeficiency virus (HIV), or other medical causes of chronic neuropathy in the baseline assessment including past medical history, any history of diabetes, alcoholism, and vitamin B deficiency

• Previous medical cannabis use for any indication within 30 days of enrollment

• Planned or actual changes in type of medications that could affect symptoms related to CIPN. New medications for the treatment of CIPN are not allowed during the study.

• Note: Subjects need to be on stable doses of CIPN medications for 4 weeks

• Strong inhibitors or inducers of CYP3A4

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent

• Clinically significant uncontrolled illness

• Diagnosis of Gilbert's disease

• Females only: Pregnant or breastfeeding

• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Related Conditions & MeSH terms

• Breast Carcinoma
• Breast Neoplasms
• Carcinoma
• Chemotherapy-Induced Peripheral Neuropathy
• Colon Carcinoma
• Peripheral Nervous System Diseases

Intervention

Drug:
• Cannabidiol
Given PO
• Delta-8-Tetrahydrocannabinol
Given PO
• Placebo Administration
Given PO

Other:
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group (FACT/GOG)-Neurotoxicity (Ntx) subscale scores	The primary analysis will compare difference in scores from the FACT/GOG-Ntx between all groups using analysis of variance, and a repeated measures analysis of variance analysis will be performed. Multivariable mixed-effects regression model which takes possible dependence of longitudinal measurements within each subject into account, will be used. In addition, a paired t-test will be utilized to compare scores between baseline and 8 and 12 weeks of treatment for each group separately.	Baseline up to week 12
Secondary	Quality of life by the Functional Assessment of Cancer Therapy-General (FACT-G) scores	The pre-treatment values recorded from the FACT-G will be considered the baseline scores. A paired T-test will be utilized to compare scores between baseline and 8 weeks of treatment. For comparisons between groups at four specific assessment points (baseline, week 4, week 8, and week 12), a repeated measures analysis of variance analysis will be performed	Up to 12 weeks
Secondary	Utilization of neuropathic and pain medications	Medication data will initially be analyzed as a dichotomous variable (yes/no) for each medication. These medications may include neuropathic medications (e.g., gabapentin, pregabalin, duloxetine, amitriptyline), Non-steroidal anti-inflammatory drugs, acetaminophen, opioid medications (e.g., morphine, oxycodone), or other related medications. Comparisons between the baseline and after-treatment medication status will be analyzed using McNemar's test. Including all the time points in the analysis of any single medication will use Cochran's Q test. The usage of multiple medications will be summarized descriptively to determine the best way to quantify multiple use, such as counts or categorized quantities. McNemar's test will be used to detect change in the level of medication use.	Up to 12 weeks
Secondary	Incidents of adverse events	All adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 6.0. The severe adverse events (SAE) (grade >= 3) will be tabulated per treatment arm and the difference of SAE will be compared among groups using chi-square test.	Up to 12 weeks