Clinical trial NCT03687034: A Study of the Safety and Pharmacokinetics of BRCX014 in Patients With Glioblastoma
Official title: A Phase I Study of BRCX014 to Investigate Dose-Ranging Safety and Pharmacokinetics in Adults With Glioblastoma (GBM) and Non-Methylated MGMT Gene Status
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Glioblastoma
Lead sponsor: Leaf Vertical Inc.
Sponsor class: INDUSTRY
First posted: 2018-09-27
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study consists of dose escalations that follow the standard 3+3 design, proceeding until the maximum tolerated dose is attained. The treatment period for patients in this study at each dose will be one year.
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Through study completion, an average of one year
Secondary outcomes:
measure: Maximum tolerated dose
timeFrame: Through study completion, an average of one year
measure: Levels of metabolites
timeFrame: Through study completion, an average of one year
measure: Progression-free survival
timeFrame: Through study completion, an average of one year
Other outcomes:
Locations:
Study officials:
affiliation: Orlando Health / UF Health Cancer Center
name: Nicholas Avgeropoulos, MD
role: PRINCIPAL_INVESTIGATOR
References: