Effects of Cannabis Use on Cancer Burden in Patients with Locally Advanced or Metastatic Solid Tumors
Although several clinical trials have studied cannabinoids for cancer pain management, there is a lack of dosing guidelines for the use of cannabinoid-based therapies in advanced cancer patients in clinical practice. There are also little to no controlled data on the effects of cannabis on other symptoms that cancer patients experience (i.e., cancer burden). Therefore, the development of larger clinical trial to examine pain, but also other outcomes related to cancer burden are needed; of particular importance is to better understand the most effective doses and to determine the overall risk/benefit profile of these doses in advanced cancer patients. This double-blind, placebo-controlled, randomized, 4-arm, phase I trial examines the safety and tolerability of a dose range of daily oral cannabis (3 active dosing arms) vs placebo (1 arm) in patients with cancer who are on an active anti-cancer therapy. Secondary outcomes include assessing: physiological effects and safety of the doses (up to 4 hrs after administration), the final tolerated dose in each active dosing arm, and impact on cancer burden score (FACT subscales). Exploratory objectives include cannabis effects on quality of life, drug effect profiles, nausea, vomiting, sleep quality, mood and other related outcomes.
Inclusion Criteria
- Histologically or cytologically confirmed locally advanced or metastatic solid tumors with any types. This applies to either newly diagnosed cancer or preexisting ones on treatment
- Patients with active cancers and currently under any line of treatment (please see notable exceptions in the exclusion criteria – patients taking checkpoint inhibitors and investigational agents will not be eligible)
- Patients have been taking their current anti-cancer therapy regimen for at least one month prior to enrollment (to ensure no safety or toxicity issues with study drug initiation)
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Total bilirubin: =< 3 X institutional upper limit of normal (at baseline)
- Aspartate aminotransferase (AST) (serum aspartate aminotransferase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]): < 3 X institutional upper limit of normal (at baseline)
- Glomerular filtration rate (GFR): ≥ 30 mL/min/1.73 m^2 using Cockcroft-Gault (at baseline)
- Normal electrocardiogram (EKG); or non-normal EKG with no significant arrhythmias or severe congestive heart failure (CHF) (at baseline)
- Patients are allowed to take any types of analgesic pain medication at baseline, but must be on a stable dose of pain medication for two weeks and not requiring rapid dose escalation
- Negative urine drug screen for all illicit drugs and THC, CBD, synthetic cannabinoids prior to randomization
- Ability to understand and the willingness to sign a written informed consent document
- Individuals able to become pregnant will agree to practice an effective form of contraception (e.g., oral birth control pills, condoms, abstinence) for the duration of enrollment (note: urine pregnancy testing will occur monthly)
- Agree to study requirements, as described in the consent form: * No driving, use of heavy machinery, or caring for children for 12 hrs after dose * Wearing fitness tracker for 4 hrs after each dose * No alcohol, marijuana (i.e., outside of provided study drug), or illegal drug use (e.g., methamphetamine, non-prescription opioids or fentanyl) for 12 hrs after dose * Daily calls so that study staff can monitor dosing * Brief weekly in-home visits * Once a month in-person visit to the University of Kentucky (UK) Center for Drug and Alcohol Research; these visits are in addition to any visits required for cancer treatment * Completing daily app questionnaires * For the first 22 days of daily dosing, agreeing to stay at home after each dose; if a participant feels comfortable leaving home after adjusting to the dose effects, they can do so, but will not be able to drive themselves
Exclusion Criteria
- History of hypersensitivity to cannabis or cannabidiol
- Current, regular use of cannabis/marijuana, THC-containing prescription medications (dronabinol/Marinol/Syndros, nabilone/Cesamet), prescription CBD (Epidiolex), or over-the-counter (OTC) CBD oil. Upon physician approval, discontinuation will be required and adequate wash-out is necessary (i.e., participant urine sample testing negative for THC and CBD upon liquid chromatography-mass spectrometry [LCMS] analysis) prior to study enrollment
- Concomitant use of the following medications (contraindicated): valproate, clobazam, warfarin, fluoxetine, disulfiram, tamoxifen, Ibrance, Gleevec, amphetamines, buprenorphine, methadone, alprazolam, p-glycoprotein substrates
- Concomitant use of checkpoint inhibitors (e.g., anti-PD1, PDL1, CTLA4)
- Current use of investigational agents, < 3 months after the use of investigational agents
- Cardiac conditions contraindicated for cannabis use, including current hypertension defined as blood pressure (BP) > 165/100; moderate/severe or unstable CHF (e.g., CHF with ejection fraction [EF] 35%), symptomatic valvular heart disease, and uncontrolled arrhythmias; investigators will consult with cardio-oncologist if needed
- Diagnosis of human papillomavirus (HPV)-related cancer, as there is some evidence that cannabis is contraindicated
- Allergy to any constituent/ingredient contained in the edible doses
- Psychiatric illness/social situations that would limit compliance with study requirements (e.g., bipolar disorder, psychosis, severe depression/anxiety). Mild/moderate mood disorders treated by medications that are not expected to increase cannabis-induced sedation/impairment are acceptable with physician approval
- Pregnant or breastfeeding
- Current moderate/severe drug or alcohol use disorder (including cannabis use disorder), positive urine drug screen for illicit drugs or cannabis, or positive alcohol (breathalyzer) during screening
- History of seizure disorder, epilepsy (controlled or uncontrolled)
- Current legal obligations (parole, probation, incarceration, urine drug screen requirements as part of parole/probation/previous incarceration)
- Currently enrolled in substance use treatment
- Self-reported cannabis and synthetic cannabinoid use in the past 30 days (medical or non-medical use is exclusionary)
- Self-reported illicit drug use in past 60 days (ex: methamphetamine, heroin, illicit fentanyl)
- Self-reported daily alcohol use
- Providing a urine sample testing positive for cannabinoids (THC, CBD) or synthetic cannabinoids (K2, spice-like compounds) via immunoassay or LCMS testing during screening; if infrequent use is reported, participant must provide additional samples testing negative for THC/CBD before randomization can be initiated
- Providing a sample testing positive for alcohol (breathalyzer) or non-medical use of other drugs (methamphetamine, cocaine) during screening; testing positive during enrollment will lead to discontinuation of the participant’s enrollment
- No access to internet/data or devices needed to participate in daily video calls
Additional locations may be listed on ClinicalTrials.gov for NCT06601218.
Locations matching your search criteria
United States
Kentucky
Lexington
PRIMARY OBJECTIVE:
I. To evaluate the safety and tolerability of daily oral cannabis administration (5 mg THC, 15 mg THC, 15 mg THC+15 mg CBD) relative to placebo in patients with cancer who are on an active anti-cancer therapy.
SECONDARY OBJECTIVES:
I. To evaluate frequency and severity of safety criteria violations from dosing to 4 hours (hrs) post-dose (heart rate [HR], oxygen [O2] saturation from fitness tracker).
II. To evaluate the percent of patients who withdrawal from the study or removed by physician/investigators for all reasons.
III. To determine final tolerated dose for future study (investigator determination after review of adverse events [AEs], participant rated visual analogue scale [VAS], vitals).
IV. To evaluate the effects of cannabis on cancer burden total score, as measured by the prostate-cancer specific National Comprehensive Cancer Network (NCCN)/Functional Assessment of Cancer Therapy (FACT-P) symptom index, a validated questionnaire that assesses cancer burden in the form of symptoms and concerns.
EXPLORATORY OBJECTIVES:
I. To assess the frequency and severity of the following symptoms that are hypothesized to be affected by cannabis, but for which little controlled data is available:
Ia. Quality of life (FACT-P subscales that assess quality of life related to physical, social/family, emotional, and functional well-being);
Ib. Drug effect profile (VAS scores assessing abuse potential, positive/aversive effects and drug tolerability; [Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), 2013; Walsh et al. 2008]; cannabis withdrawal [DSM-5, 2013]; also monitoring for suicidality [Columbia Suicide Severity Rating Scale (C-SSRS), Posner et al., 2011]);
Ic. Appetite (Functional Assessment of Anorexia/Cachexia Therapy [FAACT] anorexia/cachexia subscale [A/CS], 5 items from the subscale of appetite concerns as validated by [Gelhorn et al., 2019]; also one VAS item rating past-week general appetite);
Id. Nausea/vomiting (2 items from the Breast Cancer Prevention Trial [BCPT] subscale [Stanton et al., 2005]);
Ie. Sleep quality (Pittsburgh Sleep Quality Index; also 6 items from the brief version of the scale [Sancho-Domingo et al., 2020]);
If. General mood (Positive and Negative Affect Schedule [PANAS]; VAS scores);
Ig. Pain response (Short-form McGill Pain Questionnaire 2 [SF-MPQ-2]);
Ih. Body weight (measured at once-monthly laboratory visits);
Ii. To evaluate analgesic usage (Kentucky All Schedule Prescription Electronic Reporting System [KASPER], physician notes; self-report items created from Ren et al., 2021; Sohler et al., 2018);
Ij. Hot flashes and night sweats (particularly in those with prostate, breast cancer patients or those who present with these complaints at baseline; 2 items from the BCPT subscale [Stanton et al., 2005]).
II. Pharmacokinetic plasma concentration of novel anti-androgen therapies (abiraterone acetate, enzalutamide, or apalutamide or darolutamide) in prostate cancer patients and oral tyrosine kinase inhibitors (cabozantinib or tivozanib or lenvatinib/everolimus) in renal cancer patients.
OUTLINE: Patients are randomized to 1 of 4 arms.
ARM I: Patients receive low dose oral (PO) cannabis (THC) for 4 months. Patients also wear a fitness tracker and undergo blood sample collection on study.
ARM II: Patients receive higher dose oral (PO) cannabis (THC) for 4 months. Patients also wear a fitness tracker and undergo blood sample collection on study.
ARM III: Patients receive higher dose oral (PO) cannabis (THC + CBD) for 4 months. Patients also wear a fitness tracker and undergo blood sample collection on study.
ARM IV: Patients receive oral (PO) placebo QD for 4 months. Patients also wear a fitness tracker and undergo blood sample collection on study.
After completion of study intervention, patients are followed up at 30 days.
Trial PhasePhase I
Trial Typesupportive care
Lead OrganizationUniversity of Kentucky/Markey Cancer Center
Principal InvestigatorShanna Babalonis
- Primary ID23-MCC-CANNABIS
- Secondary IDsNCI-2024-01687
- ClinicalTrials.gov IDNCT06601218