Een Fase 1a ‘Window Trial’ naar cannabidiol (CBD) voor primaire tumoren van borstkanker

Inclusion Criteria:

1. Patients who are able to consent for surgery.

2. Histologically confirmed invasive breast cancer (stages I, II, or III) with Ki67 proliferation rate greater than or equal to 10%.

3. Women 18 years of age or older at time of consent.

4. Women of child-bearing potential (WOCBP) must agree to use an approved form of birth control and to have a negative pregnancy test result before registration. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 consecutive months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to registration:

   1. ANC ≥ 1.5 × 109/L

   2. Platelet count ≥ 100 × 109/L

   3. Hemoglobin ≥ 9 g/dL

   4. Albumin ≥ 2.5 g/dL

   5. Bilirubin ≤ 1.5 × the upper limit of normal (ULN)

   6. AST, ALT, and alkaline phosphatase ≤ 3 × ULN

   7. Serum creatinine ≤ 1.5 × ULN or creatinine clearance (CrCl) ≥ 40 mL/min on the basis of measured CrCl from a 24-hour urine collection or Cockcroft-Gault* glomerular filtration rate estimation:

      (140-age) × (weight in kg) × (0.85 if female)

      72 × (serum creatinine in mg/dL)

      • The Modification of Diet in Renal Disease (Levey et al. 2006) and the Chronic Kidney Disease Epidemiology Collaboration (Levey et al. 2009) formulas for estimation of glomerular filtration rate are also acceptable.

7. Self declared ability and capacity to comply with the study and follow-up procedures.

8. Subjects must be scheduled for surgery no less than 5 days from the planned start of day 1 and no more than 56 days from the planned start of day 1.

Exclusion Criteria:

1. Subjects undergoing neoadjuvant chemotherapy or neoadjuvant endocrine therapy.
2. Known allergy to sesame. Please note the study product contains sesame oil.
3. South Carolina State employees or anyone whose work requires THC drug testing.
4. Patients taking drugs metabolized by cytochrome p450 including warfarin, amiodarone, levothyroxine, clobazam, lamotrigine, valproate, prednisolone, hydrocortisone, clarithromycin, itraconazole, erythromycin, fluconazole, clopidogrel, rifampin, sulfamethoxazole, any opioids, and antiepileptic medications including carbamazapine, phenytoin, and valproic acid.
5. Self reported routine use of recreational or medicinal marijuana products, including over-the-counter CBD oil, Marinol®, Delta-8 THC, or cannabis (defined as > 4 times over last 30 days) or illicit drug use including opioids, cocaine, amphetamines, PCP, LSD.
6. Self reported concurrent use of over-the-counter CBD oil, Marinol®, Delta-8 THC, or cannabis.
7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to CBD or placebo.
8. Underlying history of epilepsy/ recurrent seizure disorder or unexplained seizure within past 6 months.
9. Patients with uncontrolled cardiovascular disease defined by myocardial infarction, stroke, or transient ischemic attack, or need for coronary stent placement within past six months.
10. Patients with a medical history of psychiatric illness or psychiatric symptoms that would prevent them from completing study procedures or would disqualify them from surgical intervention (e.g., untreated schizophrenia, bipolar disorder, or suicide ideation/attempt resulting in psychiatric hospitalization within the last 30 days).
11. Women who are pregnant or breastfeeding.
12. Use of blood thinners at the time of registration (warfarin, rivaroxaban, clopidogrel, and apixaban) .