Cannabis for Cancer-Related Symptoms

(CAFCARS Trial)

Recruiting at 7 trial locations

Overseen By Alshanee Sharma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pippa Hawley

Must not be taking: CYP1A1, 1A2, 1B1 drugs

Disqualifiers: Substance misuse, Psychosis, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16-48 days

150 Participants Needed

Trial Summary

What is the purpose of this trial?

Clinical evidence is urgently needed to be able to advise patients on which cannabis-based products to take, or to avoid, in managing cancer-related symptoms. This trial was therefore designed to determine which cannabis extract combination (High THC-Low CBD, Low THC-High CBD, or Equal amounts of THC and CBD) is most effective at treating cancer related symptoms for each patient relative to placebo. Investigators propose a randomized, double-blind, N-of-1 trial to test the effectiveness of each cannabis extract combination using cannabis oils in a minimum of 120 patients on 4 cancer-related symptoms: nausea, pain, anxiety and sleep disturbance. The three active treatments will be the following cannabis oil extract combinations: High THC/Low CBD, Low THC/High CBD, and Equal amounts of THC/CBD. * THC = Tetrahydrocannabinol * CBD = Cannabidiol The placebo treatment will be Medium Chain Triglyceride (MCT) oil. The active oils and the placebo are similar in taste, smell and effectively blind subjects. Primary objective: To identify whether there is an active cannabis extract that is more effective than placebo in managing overall cancer-related symptoms for individual subjects who completed at least 1 treatment cycle for the entire patient population represented by those individual subjects, and for subsets of that subject population defined by relevant baseline patient characteristics. Secondary objective: To identify whether there is a cannabis extract that is more effective than placebo in managing each of the 4 index symptoms (pain, nausea, anxiety and sleep disturbance) for individual subjects who completed at least 1 treatment cycle, for the entire patient population represented by those individual subjects, and for subsets of that subject population defined by relevant baseline patient characteristics. Tertiary objectives: To investigate the safety (e.g., serious adverse events) of each of the three cannabis extracts. To identify subject preference of each of the 4 oils (if any).

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, if you are taking medications that might interact with cannabinoids (CYP1A1, 1A2, and 1B1), you may need to switch to a different medication. Please consult with the trial team for specific guidance.

What data supports the idea that Cannabis for Cancer-Related Symptoms is an effective treatment?

The available research shows that cannabis can help manage cancer-related symptoms like pain, nausea, and loss of appetite. It is particularly effective for chemotherapy-induced nausea and vomiting, and it can also improve sleep quality and reduce anxiety. While cannabis might not be as strong as some other treatments for nausea, it is unique because it also boosts appetite. Both THC and CBD, the main components of cannabis, have shown benefits. THC is better for improving sleep, while CBD can be just as effective for other symptoms. Overall, cannabis offers a range of benefits for cancer patients, making it a valuable option for symptom relief. ^{1 2 3 4 5}

What safety data exists for cannabis in treating cancer symptoms?

The provided research does not directly address the safety data for cannabis or its derivatives like THC and CBD in treating cancer-related symptoms. The studies focus on general adverse event reporting in cancer therapies, pharmacovigilance, and patient-reported outcomes, but do not specifically mention cannabis or cannabinoids. Therefore, specific safety data for cannabis in this context is not available in the given research. ^{6 7 8 9 10}

Is cannabis a promising drug for cancer-related symptoms?

Yes, cannabis shows promise in treating cancer-related symptoms. It can help improve appetite, reduce nausea and vomiting, and relieve pain in cancer patients. Some studies suggest that cannabinoids, like THC and CBD, may also have anti-cancer properties, although more research is needed to confirm these effects in humans. ^{4 11 12 13 14}

Research Team

Philippa Hawley, FRCPC

Principal Investigator

BC Cancer

Eligibility Criteria

This trial is for adults over 19 with stable cancer-related symptoms like nausea, pain, anxiety, or sleep issues. Participants must not use other cannabis products during the study and should have a life expectancy of at least 4 months. They can't join if they're pregnant, on another trial, have certain mental health conditions or substance misuse disorders.

Inclusion Criteria

I can be reached by phone.

Willing to commit to not taking cannabis in any form other than the study products for the duration of the study

I am 19 years old or older.

Exclusion Criteria

They have any concurrent condition likely to interfere with completion of the study protocol, such as allergy to any component of the study products

I cannot or will not avoid using heavy machinery during the study.

They have an active psychiatric disorder likely, in the investigator's opinion, to interfere with adherence to study protocol

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a series of N-of-1 trials with cannabis oil extracts and placebo for cancer-related symptom management

16-48 days

Daily self-administration with regular monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Cannabis

Trial Overview The trial tests three types of cannabis oil extracts (High THC/Low CBD, Low THC/High CBD, Equal THC/CBD) against a placebo to see which is best for managing cancer-related symptoms. Each participant will try all options in random order to compare effectiveness and safety.

Participant Groups

Group I: Low THC/High CBD Cannabis Oil Experimental Treatment 1 Intervention

THC+THCa = 37mg CBD+CBDA = 784mg Total cannabinoids = 821mg (1.37mg/drop) Dried marijuana equivalent = 6g

Group II: High THC/Low CBD Cannabis Oil Experimental Treatment 1 Intervention

THC+THCa = 573 mg CBD+CBDA = 0 mg Total cannabinoids = 573 mg (0.95mg/drop) Dried marijuana equivalent = 5g

Group III: Equal amounts of THC/CBD Cannabis Oil Experimental Treatment 1 Intervention

THC+THCa = 516mg CBD+CBDA = 456mg Total cannabinoids = 972mg (1.62mg/drop) Dried marijuana equivalent = 6g

Group IV: Placebo Oil Placebo Group 1 Intervention

Medium Chain Triglyceride (MCT) oil

Cannabis is already approved in Canada, United States, European Union for the following indications:

Approved in Canada as Cannabis for:

• Chronic pain
• Nausea and vomiting associated with chemotherapy
• Spasticity associated with multiple sclerosis

Approved in United States as Cannabis for:

• Seizures associated with Lennox-Gastaut syndrome and Dravet syndrome
• Nausea and vomiting associated with chemotherapy

Approved in European Union as Cannabis for:

• Spasticity associated with multiple sclerosis
• Chronic pain

Who Is Running the Clinical Trial?

Pippa Hawley

Lead Sponsor

Trials

2

Recruited

330+

Findings from Research

Cannabidiol (CBD), a non-intoxicating compound from Cannabis sativa, shows a wide range of therapeutic effects that may be beneficial in managing cancer, based on both preclinical and clinical research.

The article discusses potential mechanisms of action for CBD in cancer treatment and suggests that it could be effectively integrated with traditional cancer therapies to help manage side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol (CBD) in Cancer Management. O'Brien, K.[2022]

Cannabis and cannabinoid-based medicines have shown favorable outcomes in alleviating chemotherapy-induced nausea and vomiting, as well as managing cancer-related pain, suggesting they can be beneficial in palliative oncology.

While short- and long-term side effects of cannabis use appear manageable and diminish after stopping the drug, further research is necessary to fully understand its efficacy and safety before it can be integrated into standard oncology treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis Use in Palliative Oncology: A Review of the Evidence for Popular Indications. Turgeman, I., Bar-Sela, G.[2017]

Cannabis has potential benefits for cancer patients, particularly in managing symptoms like nausea, pain, and appetite loss, and may be the only effective treatment for some individuals.

Emerging evidence suggests that cannabinoids may have direct anticancer effects through mechanisms like promoting cell death and inhibiting tumor growth, although more human studies are needed to confirm these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating cannabis into clinical cancer care. Abrams, DI.[2018]

Cannabidiol (CBD), a non-psychoactive compound from Cannabis sativa L., shows promising anti-tumor effects across various cancer types, as highlighted by recent in vitro and in vivo studies.

CBD exhibits multiple mechanisms of action, including anti-proliferative, pro-apoptotic, and anti-inflammatory properties, making it a potential therapeutic option in cancer treatment with a favorable pharmacological profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabidiol-from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer. Kis, B., Ifrim, FC., Buda, V., et al.[2023]

In a study of 108 oncology patients, both THC-dominant and CBD-dominant cannabis treatments showed significant improvements in various cancer-related symptoms, including pain intensity and sleep quality, over a one-month period.

There were no significant safety differences among THC-dominant, CBD-dominant, and mixed cannabis treatments, suggesting that CBD-dominant products can be effective alternatives to THC-dominant products for managing cancer symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-Term Medical Cannabis Treatment Regimens Produced Beneficial Effects among Palliative Cancer Patients. Aviram, J., Lewitus, GM., Vysotski, Y., et al.[2020]

Modern multimodal tumor therapies, which include radiotherapy, chemotherapy, immunotherapy, and targeted therapies, can lead to significant acute and long-lasting side effects that negatively impact patients' quality of life and survival.

The paper highlights the need for better characterization of side effects from newly approved therapies and provides recommendations for monitoring and managing these effects in specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology. Rassaf, T., Totzeck, M., Backs, J., et al.[2021]

In a multicenter clinical trial involving 152 lung cancer patients, the use of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) allowed for high compliance in self-reporting adverse events, particularly during treatment (86% compliance).

The study demonstrated that patients were willing to self-report their symptoms using tablet computers, and identified that improving data collection methods, such as allowing electronic reporting between visits, could further enhance compliance and data quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial. Basch, E., Pugh, SL., Dueck, AC., et al.[2022]

Patient forums can significantly enhance pharmacovigilance by providing real-time, uncensored reports of adverse drug events (ADEs) for rare cancers, as demonstrated in a case study on Gastrointestinal Stromal Tumor patients.

Using machine learning algorithms, the study identified that certain side effects, like cognitive impairment and alopecia from avapritinib, were reported at different rates compared to clinical trials, highlighting the potential of patient forums to uncover long-term and novel ADEs not previously documented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated gathering of real-world data from online patient forums can complement pharmacovigilance for rare cancers. Dirkson, A., Verberne, S., Kraaij, W., et al.[2022]

A review of 166 phase III randomized clinical trials published between 2011 and 2013 revealed frequent misreporting of adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE v3.0), indicating a significant issue in adherence to established guidelines.

Inappropriate grading of toxicities was common, with serious conditions like febrile neutropenia often graded too low, and less severe conditions like alopecia graded too high, which could mislead clinicians and affect treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use and misuse of common terminology criteria for adverse events in cancer clinical trials. Zhang, S., Liang, F., Tannock, I.[2018]

The study involved 127 cancer patients undergoing chemotherapy or radiation therapy, and it confirmed that most adverse event (AE) terms in the PRO-CTCAE library were easily understood by patients, regardless of their education level.

Minor modifications were made to 17 AE terms to enhance clarity and comprehension, ultimately supporting the content validity of the PRO-CTCAE for accurately capturing patient-reported outcomes during cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive interviewing of the US National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Hay, JL., Atkinson, TM., Reeve, BB., et al.[2022]

There is inconsistent evidence linking cannabis smoking to cancers of the respiratory system, with some case reports in young adults but no strong epidemiological support.

While THC and cannabinoids may help alleviate cancer symptoms like nausea and pain, there is currently no evidence of their anticancer effects in humans, highlighting the need for safe medical use without psychoactive side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoids and cancer: causation, remediation, and palliation. Hall, W., Christie, M., Currow, D.[2022]

Medical cannabis, particularly formulations containing THC and CBD, shows potential for managing cancer-associated pain, with some studies indicating effective pain relief at doses as low as 2.7 mg THC combined with CBD.

Despite some positive findings, many studies had small sample sizes and lacked statistical power, highlighting the need for larger, well-designed clinical trials to better understand the efficacy and optimal dosing of cannabis-based therapies for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A selective review of medical cannabis in cancer pain management. Blake, A., Wan, BA., Malek, L., et al.[2022]

Cannabinoids, particularly CBD and Δ9-THC, have shown potential in preclinical studies for treating various cancers, including leukemia and glioblastoma, by blocking tumor cell growth and inducing apoptosis.

Cannabinoid-based products are approved for medical use in cancer patients and have a favorable safety profile, although psychoactive effects and poor bioavailability can limit their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabis and its constituents for cancer: History, biogenesis, chemistry and pharmacological activities. Lal, S., Shekher, A., Puneet, ., et al.[2021]

THC, CBD, and standardized cannabis extracts (F1) effectively inhibited the migration and invasion of human breast cancer cells (MCF-7) by targeting multiple signaling pathways, including FAK, Akt, and NF-κB.

CBD and F1 also induced apoptosis in MCF-7 cells through the Bcl-2/caspase-3 pathways, suggesting their potential as therapeutic agents in preventing breast cancer metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cannabinoids and standardized cannabis extracts inhibit migration, invasion, and induce apoptosis in MCF-7 cells through FAK/MAPK/Akt/NF-κB signaling. Suttithumsatid, W., Sukketsiri, W., Panichayupakaranant, P.[2023]

References

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Cannabidiol (CBD) in Cancer Management. [2022]

2. Israel pubmed.ncbi.nlm.nih.gov

Cannabis Use in Palliative Oncology: A Review of the Evidence for Popular Indications. [2017]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Integrating cannabis into clinical cancer care. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Cannabidiol-from Plant to Human Body: A Promising Bioactive Molecule with Multi-Target Effects in Cancer. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Short-Term Medical Cannabis Treatment Regimens Produced Beneficial Effects among Palliative Cancer Patients. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

Onco-Cardiology: Consensus Paper of the German Cardiac Society, the German Society for Pediatric Cardiology and Congenital Heart Defects and the German Society for Hematology and Medical Oncology. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Automated gathering of real-world data from online patient forums can complement pharmacovigilance for rare cancers. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Use and misuse of common terminology criteria for adverse events in cancer clinical trials. [2018]

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Cognitive interviewing of the US National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). [2022]

11. England pubmed.ncbi.nlm.nih.gov

Cannabinoids and cancer: causation, remediation, and palliation. [2022]

12. China pubmed.ncbi.nlm.nih.gov

A selective review of medical cannabis in cancer pain management. [2022]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Cannabis and its constituents for cancer: History, biogenesis, chemistry and pharmacological activities. [2021]

14. England pubmed.ncbi.nlm.nih.gov

Cannabinoids and standardized cannabis extracts inhibit migration, invasion, and induce apoptosis in MCF-7 cells through FAK/MAPK/Akt/NF-κB signaling. [2023]