Promising Early Results for Use of an Oral THC/CBD Extract As Secondary Prophylaxis in the Setting of CINV
Results of the phase 2 crossover component of a phase 2/3 study designed to evaluate the safety and efficacy of an oral formulation of a tetrahydrocannabinol (THC)/cannabidiol (CBD) cannabis extract in the secondary prevention of patients experiencing chemotherapy-induced nausea and vomiting (CINV) revealed that most patients preferred this treatment compared with placebo. These findings were accepted for presentation at the ASCO2 Virtual Scientific Program and released on May 29, 2020.
Despite the use of guideline-concordant prophylaxis for CINV, many patients treated with moderately or highly emetogenic chemotherapy experience these often dreaded adverse effects of chemotherapy, even following the administration of secondary/rescue antiemetic therapy.
The design of this multicenter, placebo-controlled, double-blinded, crossover, phase 2 clinical trial (ACTRN12616001036404), which has been previously described, 2 involved enrollment of adult patients with cancer of any type or stage undergoing treatment with moderately or highly emetogenic chemotherapy who reported significant vomiting and/or nausea in the previous cycle of chemotherapy despite receiving guideline-concordant antiemetic therapy. All enrolled patients were scheduled to have at least 2 additional chemotherapy cycles.
Starting on 1 day prior to the first day of the first chemotherapy cycle following study enrollment (A), and continuing through day 5 following initiation of that cycle of chemotherapy, oral THC 2.5 mg/CBD 2.5 mg capsules were administered 3 times daily to study patients and could be titrated to 1 to 4 times daily based on patient response. All study patients then crossed over to receive oral placebo capsules on the same schedule for the second chemotherapy cycle (B). Hence, each patient essentially served as their own control. Guideline-recommended CINV prophylactic therapy was also administered to all patients prior to initiation of each chemotherapy cycle.
The primary endpoint of the phase 2 study involved determination of the percentages of patients reporting a complete response (ie, CR, defined as no nausea or use of rescue medications) between 0 and 120 hours following chemotherapy initiation.
Key secondary study end points included safety preference for cycle A or B study intervention, as well as the percentage of patients experiencing no emesis, no significant nausea, and no use of rescue medication up to 120 hours following initiation of chemotherapy.
Of the 72 patients included in the efficacy analysis who completed at least 2 chemotherapy cycles following study enrollment, the median age was 55 years, approximately three-quarters were female, 58% reported previous use of cannabis (although use of other sources of cannabis were not permitted during the study), and 55% received potentially curative therapy. The most commonly received chemotherapy regimen was a doxorubicin plus cyclophosphamide-based regimen, which was administered to 26% of patients.
Significantly higher rates of CR (25% vs 14%; P =.04), no significant nausea (21% vs 10%; P =.03), and use of rescue medication (28% vs 15%; P =.03) were reported during cycle A compared with cycle B, respectively. The study endpoint of no emesis was reported by 69% and 57% of patients for cycle A and cycle B, respectively (P =.05).
Notably, 83% of patients reported a preference for the study intervention administered in cycle A over that given to them during cycle B.
For the 78 patients included in the safety analysis, no serious adverse events were attributed to THC/CBD, although reported frequencies of sedation (19% vs 4%), dizziness (10% vs 1%), and disorientation (3% vs 0%) were higher during administration of THC/CBD compared with placebo, respectively.
Some of the study limitations identified by the study presenter Peter Grimison, MBBS, MPH, PhD, FRACP, clinical associate professor at the Chris O’Brien Lifehouse, Sydney Cancer Center in New South Wales, included concomitant use of olanzapine in only 4% of patients, and nonparticipation of a high percentage of those initially identified as being eligible for the study (due to current cannabis use, refusal to stop driving during study duration, psychiatric comorbidities, and because of the crossover design of the study, as well as other reasons).
“Based on these positive results, the definitive parallel phase 3 trial component continues to accrue,” Dr Grimison noted in his concluding remarks.
Disclosure: Research funding for this study of a proprietary formulation of a cannabis extract developed by Tilray was provided by the New South Wales Ministry of Health. For a full list of disclosures, please refer to the study abstract.
Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.
Medical Cannabis During Chemoradiation for Head and Neck Cancer
Blood (less than 10 mL in an EDTA tube), urine (less than 15 mL), and oral swab samples will be collected from patients at baseline, once during weeks 1-2, once during week 5-6, and at the time of post-treatment follow-up appointments. These collections are included in the Study Calendar (section 4.6). Blood tests are routinely performed on a weekly basis for patients receiving systemic therapy and we will make all attempts to coordinate biospecimen collection for study purposes with biospecimen collection for standard clinical care in order to minimize patient inconvenience.
Each specimen will be analyzed in the Stable Isotope & Metabolomics Core Facility of the Diabetes Research Center under the direction of Dr. Irwin Kurland. We will test each sample for over 150 metabolites that are involved in pathways such as the urea cycle, fatty acid metabolism, and spermidine and spermine metabolism.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
|Sampling Method:||Non-Probability Sample|
- Patients must have histologically confirmed squamous cell carcinoma of the head and neck region planned for definitive or adjuvant treatment with concurrent radiation therapy and systemic therapy
- Patients may receive platinum-based chemotherapy or cetuximab concurrently with radiation therapy
- Age >18 years and ECOG performance status <2 (Karnofsky >60).
- Patients must be willing to use medically certified cannabis as directed after study enrollment
- Patients must be able to read English, Spanish, or French fluently
- Ability to understand and the willingness to sign a written informed consent document.
- Prior diagnosis of cannabis use disorder as defined in the DSM-V
- Current opioid use disorder on maintenance opioid therapy
- Current active use of smoked cannabis or cannabis derivatives AND unwillingness to cease use of non-medically certified cannabis for the duration of study participation.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to cannabis derivatives
- Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.