A Study of the Safety and Pharmacokinetics of BRCX014 in Patients With Glioblastoma

A Phase I Study of BRCX014 to Investigate Dose-Ranging Safety and Pharmacokinetics in Adults With Glioblastoma (GBM) and Non-Methylated MGMT Gene Status

An Open-Label, Multi-Center Study to Assess the Safety and Pharmacokinetics of BRCX014 Combined with Standard-of-Care Treatment in Subjects with Glioblastoma

Several studies have shown a possible anti-tumor role for cannabinoids by modulating cell signaling pathways, inhibiting angiogenesis, inducing apoptosis, and overcoming chemotherapy resistance. The investigators seek to demonstrate the safety profile of BRCX014, a cannabinoid formulation, when given to glioblastoma patients in conjunction with standard-of-care therapy.

Inclusion Criteria:

• Histopathologically confirmed glioblastoma (astrocytoma WHO grade IV)

• MGMT promoter methylation status is negative

• Brain MRI confirmation of disease according to RANO (Response Assessment in Neuro-Oncology) criteria

• Completion of standard-of-care temozolomide-based chemoradiation for post-operative treatment of glioblastoma plus two-to-six week "washout" period and stable-to-improved baseline brain MRI.

• Male and female subjects between the ages of 18 and 85 years

• Karnofsky Performance Score ≥ 60%

• Expected survival of at least six months from the day of enrollment

• No severe dysfunction of major organs (e.g., bone marrow, liver, kidneys, heart, lungs, etc.) and laboratory results from up to 14 days prior to enrollment fall within criteria:

  • Hemoglobin > 10 g/dL
  • Leukocytes ≥ 3,000 per μl
  • Absolute neutrophil count ≥ 1,500 per μl
  • Platelet count > 100,000 per μl
  • BUN < 25 mg
  • Serum creatinine within normal institutional limits OR Creatinine clearance ≥ 60 ml/min/1.73 m2 for patients with creatinine levels above institutional normal
  • Total serum bilirubin within normal institutional limits
  • ALT (SGPT) ≤ 2.5× the institutional upper limit of normal OR AST (SGOT) ≤ 2.5× the institutional upper limit of normal

• Ability to take medication sublingually

• Willingness and ability to comply with scheduled visits, laboratory tests, and other trial procedures

• Accessible for treatment and follow-up

• Female subjects: Use of two approved forms of contraceptives

• Male subjects: Use of two approved forms of contraceptives and willing to instruct their partners to use one form of contraceptive as well

• Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

• MGMT promoter methylation status is positive (i.e., promoter is methylated)
• Prior radiotherapy for GBM within two (2) weeks of entering the study or has not recovered from adverse events due to agents administered more than four (4) weeks earlier
• Prior chemotherapy, immunotherapy, or radiation therapy for other cancers (except for treatment of limited curable skin cancers)
• Currently or recently (in the previous six months) part of a clinical trial involving any other investigational agents
• Hypersensitivity or allergy to any ingredient in the study drug
• Receiving any medications or substances that are known substantial inhibitors or inducers of CYP3A4
• Consumption of grapefruit or grapefruit juice three (3) days prior to screening or unwillingness to abstain from consuming grapefruit in any form during the study
• Uncontrolled intercurrent illness that would limit compliance with study requirements
• Pregnancy, possible pregnancy, plans for pregnancy, or active lactation or nursing
• Positive HIV or hepatitis status
• Unwillingness or inability to take medication sublingually
• Diagnosis of cancer more than 120 days prior to initial visit
• History of prior malignancy except curatively treated skin cancers
• History of prior chemotherapy or radiation for other cancers (except for treatment of limited curable skin cancers) before initial visit
• Clinically significant unstable medical conditions other than GBM
• Clinically relevant symptoms or clinically significant illness in the four (4) weeks prior to screening or registration, other than GBM
• Clinically significant unstable medical conditions, other than GBM, deemed by the investigator to pose an unacceptable risk to the patient
• History of substance abuse within the last two years
• Current use of recreational or medicinal cannabis, synthetic cannabinoid-based medications, or alcohol, or planned use while in the study
• Evidence of any diseases or conditions that may interfere with the study or interpretation of study results
• Inability or unwillingness to cooperate with the study procedures
• Known history of severe depression or psychiatric disorders, or active suicidal ideation
• Subjects with close affiliation with an investigational site
• Absence of or unwillingness to sign and date the informed consent document