A Study of the Efficacy of Cannabidiol in Patients With Multiple Myeloma, Glioblastoma Multiforme, and GI Malignancies

Several studies have shown a potential anti-tumor role for cannabinoids by modulating cell signaling pathways, inhibiting angiogenesis, inducing apoptosis, and overcoming chemotherapy resistance. In phase I trials, cannabinoids have been shown to enhance the uptake of chemotherapy into malignant cells without affecting normal cells. The investigators seeks to demonstrate that the combination of chemotherapy with BRCX014 will have a greater anti-tumor and anti-proliferative activity when compared to standard of care alone.

• Cannabidiol (Drug), also known as BRCX014, bioRenovate CX: * Sublingual dose of 1 mL (0.910 g) of BRCX014 in the morning, prior to the first meal of the day * Sublingual dose of 1 mL (0.910 g) of BRCX014 in the afternoon, prior to the evening meal
• Bortezomib (Drug), also known as Velcade: Standard of care (SOC) chemotherapy for multiple myeloma will include a bortezomib-based regimen given at 1.3 mg/m2 on days 1, 4, 8 \& 11 schedule to be repeated every 21 days.
• Leucovorin (Drug), also known as Folinic acid: Standard of care chemotherapy for Stage IV colon or rectal cancer, will include leucovorin 350 mg/m2 IV over 2 hours Day 1, 5-FU 400 mg/m2 IV bolus followed 2400 mg/m2 IV over 46 hours, oxaliplatin 100 mg/m2 IV Day 1, bevacizumab 5 mg/kg IV day1. Irinotecan can be substituted for oxaliplatin.
• 5-FU (Drug), also known as Efudex: Standard of care chemotherapy for Stage IV colon or rectal cancer, will include leucovorin 350 mg/m2 IV over 2 hours Day 1, 5-FU 400 mg/m2 IV bolus followed 2400 mg/m2 IV over 46 hours, oxaliplatin 100 mg/m2 IV Day 1, bevacizumab 5 mg/kg IV day1. Irinotecan can be substituted for oxaliplatin.
• Oxaliplatin (Drug), also known as Eloxatin: Standard of care chemotherapy for Stage IV colon or rectal cancer, will include leucovorin 350 mg/m2 IV over 2 hours Day 1, 5-FU 400 mg/m2 IV bolus followed 2400 mg/m2 IV over 46 hours, oxaliplatin 100 mg/m2 IV Day 1, bevacizumab 5 mg/kg IV day1. Irinotecan can be substituted for oxaliplatin.
• Bevacizumab (Drug), also known as Avastin: Standard of care chemotherapy for Stage IV colon or rectal cancer, will include leucovorin 350 mg/m2 IV over 2 hours Day 1, 5-FU 400 mg/m2 IV bolus followed 2400 mg/m2 IV over 46 hours, oxaliplatin 100 mg/m2 IV Day 1, bevacizumab 5 mg/kg IV day1. Irinotecan can be substituted for oxaliplatin.
• Irinotecan (Drug), also known as Camptosar: Standard of care chemotherapy for Stage IV colon or rectal cancer, will include leucovorin 350 mg/m2 IV over 2 hours Day 1, 5-FU 400 mg/m2 IV bolus followed 2400 mg/m2 IV over 46 hours, oxaliplatin 100 mg/m2 IV Day 1, bevacizumab 5 mg/kg IV day1. Irinotecan can be substituted for oxaliplatin.
• Gemcitabine (Drug), also known as Gemzar: Stage IV pancreatic cancer will include a gemcitabine-based regiment at 1000 mg/m2 day 1, 7, 15 of a 21-day cycle.
• Temozolomide (Drug), also known as Temodar: Standard of care chemotherapy for patients with glioblastoma multiforme includes concurrent radiation therapy (2 Gy per day for a total of 60 Gy) and temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle).

Primary outcomes

• Response rate [Through study completion, an average of one year]: The primary objective of this study is to evaluate the overall response rates of cancer patients as assessed by standard criteria.

Secondary outcomes

• Time to progression (TTP) in patients using lab results and radiographic data. [Through study completion, an average of one year]: A secondary objective of this study is to measure TTP using lab results and radiographic data.
• Progression-free survival (PFS) in patients using lab results and radiographic data. [Through study completion, an average of one year]: A secondary objective of this study is to measure PFS using lab results and radiographic data.
• Quality-of-life assessment in patients using patient-reported outcomes (PRO) data. [Through study completion, an average of one year]: A secondary objective of this study is to collect patient-reported outcomes (PRO) data.
• Quality-of-life assessment in patients using clinician-reported outcomes (ClinRO) data. [Through study completion, an average of one year]: A secondary objective of this study is to collect clinician-reported outcomes (ClinRO) data.

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Signed and dated informed consent
2. Male and Females age 18 to 80 years old at the time of screening
3. Confirmed tissue diagnosis of Multiple myeloma, GI malignancy by a licensed pathologist
4. A performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.
5. Females of childbearing potential willing to utilize two approved forms of contraceptives (e.g., birth control, abstinence, spermicidal lube, intrauterine device \[IUD\])
6. Male study subjects must be willing to use two approved forms of contraceptives (e.g., physical barrier-condoms, abstinence, spermicidal lube)

Exclusion Criteria:

1. Subject is pregnant or plans to become pregnant or actively lactating/nursing
2. Hypersensitivity to any ingredient in the study product
3. Initial laboratory values as determined by the principal investigator to be clinically significant
4. A substance abuse history within the last five years
5. Any diseases or conditions that may interfere with the conduct of the study or interpretation of the study results
6. .Close affiliation with the investigational site (e.g., a close relative of the investigator), dependent person (employee or student of investigational site, or sponsor's staff)
7. Currently enrolled in another investigational clinical study
8. A known history of severe depression or psychiatric disorders or active suicidal ideation
9. Inability or unwillingness to cooperate with the study procedures for any reasons

• Sarah F Katta, DO, Principal investigator, Leaf Vertical Inc.