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

Study Overview
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Brief Summary
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A Randomized, Double-Blind, Placebo-Controlled, Parallel, Multi-Center Study to Assess the Efficacy of BRCX014 Combined with Standard-Of-Care Treatment in Subjects with Glioblastoma Multiforme, Multiple Myeloma, and GI Malignancies

Detailed Description
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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.

Official Title
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Randomized Double-Blind, Placebo-Controlled Parallel Multi-Center Study to Assess the Efficacy of Cannabidiol (BRCX014) Combined With Standard-Of-Care Treatment in Subjects With Multiple Myeloma, Glioblastoma Multiforme, and GI Malignancies

Conditions
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Cancer of Liver, Cancer of Pancreas, Cancer of Rectum, Cancer of Colon, Cancer, Gall Bladder, Myeloma Multiple, Glioblastoma Multiforme

Intervention / Treatment
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* Drug: Cannabidiol
* Drug: Bortezomib
* Drug: Leucovorin
* Drug: 5-FU
* Drug: Oxaliplatin
* Drug: Bevacizumab
* Drug: Irinotecan
* Drug: Gemcitabine
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed and dated informed consent Male and Females age 18 to 80 years old at the time of screening Confirmed tissue diagnosis of Multiple myeloma, GI malignancy by a licensed pathologist A performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale. Females of childbearing potential willing to utilize two approved forms of contraceptives (e.g., birth control, abstinence, spermicidal lube, intrauterine device [IUD]) Male study subjects must be willing to use two approved forms of contraceptives (e.g., physical barrier-condoms, abstinence, spermicidal lube) Exclusion Criteria: Subject is pregnant or plans to become pregnant or actively lactating/nursing Hypersensitivity to any ingredient in the study product Initial laboratory values as determined by the principal investigator to be clinically significant A substance abuse history within the last five years Any diseases or conditions that may interfere with the conduct of the study or interpretation of the study results .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) Currently enrolled in another investigational clinical study A known history of severe depression or psychiatric disorders or active suicidal ideation Inability or unwillingness to cooperate with the study procedures for any reasons

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Study length for randomized patients in the treatment group(s) will be 180 days. For those subjects randomized into the control group(s), after 90 days of the control group study treatment, will be given the choice to rollover into the treatment group. Crossover is also permitted if there is progression of disease before 90 days.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Colon: Chemo + Placebo<br>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. | Drug: Leucovorin<br>* 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.<br>* Other names: Folinic acid;Drug: 5-FU<br>* 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.<br>* Other names: Efudex;Drug: Oxaliplatin<br>* 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.<br>* Other names: Eloxatin;Drug: Bevacizumab<br>* 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.<br>* Other names: Avastin;Drug: Irinotecan<br>* 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.<br>* Other names: Camptosar;|
| Experimental: Colon: Chemo + BRCX014<br>Cannabidiol (BRCX014) 200 mg daily plus 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. | Drug: Cannabidiol<br>* 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<br>* Other names: bioRenovate CX;Drug: Leucovorin<br>* 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.<br>* Other names: Folinic acid;Drug: 5-FU<br>* 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.<br>* Other names: Efudex;Drug: Oxaliplatin<br>* 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.<br>* Other names: Eloxatin;Drug: Bevacizumab<br>* 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.<br>* Other names: Avastin;Drug: Irinotecan<br>* 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.<br>* Other names: Camptosar;|
| Placebo Comparator: Rectal: Chemo + Placebo<br>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. | Drug: Leucovorin<br>* 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.<br>* Other names: Folinic acid;Drug: 5-FU<br>* 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.<br>* Other names: Efudex;Drug: Oxaliplatin<br>* 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.<br>* Other names: Eloxatin;Drug: Bevacizumab<br>* 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.<br>* Other names: Avastin;Drug: Irinotecan<br>* 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.<br>* Other names: Camptosar;|
| Experimental: Rectal: Chemo + BRCX014<br>Cannabidiol (BRCX014) 200 mg daily plus 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. | Drug: Cannabidiol<br>* 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<br>* Other names: bioRenovate CX;Drug: Leucovorin<br>* 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.<br>* Other names: Folinic acid;Drug: 5-FU<br>* 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.<br>* Other names: Efudex;Drug: Oxaliplatin<br>* 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.<br>* Other names: Eloxatin;Drug: Bevacizumab<br>* 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.<br>* Other names: Avastin;Drug: Irinotecan<br>* 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.<br>* Other names: Camptosar;|
| Placebo Comparator: Multiple myeloma: Chemo + Placebo<br>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. | Drug: Bortezomib<br>* 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.<br>* Other names: Velcade;|
| Experimental: Multiple myeloma: Chemo + BRCX014<br>Cannabidiol (BRCX014) 200 mg daily plus 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. | Drug: Cannabidiol<br>* 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<br>* Other names: bioRenovate CX;Drug: Bortezomib<br>* 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.<br>* Other names: Velcade;|
| Placebo Comparator: Pancreatic: Chemo + Placebo<br>Stage IV pancreatic cancer will include a gemcitabine-based regiment at 1000 mg/m2 day 1, 7, 15 of a 21-day cycle. | Drug: Gemcitabine<br>* Stage IV pancreatic cancer will include a gemcitabine-based regiment at 1000 mg/m2 day 1, 7, 15 of a 21-day cycle.<br>* Other names: Gemzar;|
| Experimental: Pancreatic: Chemo + BRCX014<br>Cannabidiol (BRCX014) 200 mg daily plus Stage IV pancreatic cancer will include a gemcitabine-based regiment at 1000 mg/m2 day 1, 7, 15 of a 21-day cycle. | Drug: Cannabidiol<br>* 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<br>* Other names: bioRenovate CX;Drug: Gemcitabine<br>* Stage IV pancreatic cancer will include a gemcitabine-based regiment at 1000 mg/m2 day 1, 7, 15 of a 21-day cycle.<br>* Other names: Gemzar;|
| Placebo Comparator: GBM: Chemo + Placebo<br>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). | Drug: Temozolomide<br>* 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).<br>* Other names: Temodar;|
| Experimental: GBM: Chemo + BRCX014<br>Cannabidiol (BRCX014) 200 mg daily plus 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). | Drug: Cannabidiol<br>* 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<br>* Other names: bioRenovate CX;Drug: Temozolomide<br>* 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).<br>* Other names: Temodar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | The primary objective of this study is to evaluate the overall response rates of cancer patients as assessed by standard criteria. | Through study completion, an average of one year | 

Secondary Outcome Measures

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