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

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

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

Study Overview

• Status: Unknown
• Conditions: Glioblastoma Multiforme; Cancer of Liver; Cancer of Pancreas; Cancer of Colon; Myeloma Multiple; Cancer of Rectum; Cancer, Gall Bladder
• Intervention / Treatment: Drug: Leucovorin; Drug: 5-FU; Drug: Oxaliplatin; Drug: Bevacizumab; Drug: Irinotecan; Drug: Cannabidiol; Drug: Bortezomib; Drug: Gemcitabine; Drug: Temozolomide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: William Fisher; Phone Number: 407-797-2332; Email: ceo@leafvertical.com
• Study Contact Backup: Name: Philip Arlen, PhD; Phone Number: 407-443-0656; Email: parlen@leafvertical.com

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • Southwest Cancer Center
      • Contact: Philip Arlen, PhD; Phone Number: 407-443-0656; Email: parlen@leafvertical.com
      • Contact: Sarah Katta, DO; Phone Number: 407-426-8660; Email: sarahfk1978@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

10

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Leaf Vertical Inc.
• Investigators: Principal Investigator: Sarah F Katta, DO, Leaf Vertical Inc.

Study record dates

Study Major Dates

• Study Start (Anticipated): January 15, 2019
• Primary Completion (Anticipated): June 30, 2020
• Study Completion (Anticipated): December 15, 2020

Study Registration Dates

• First Submitted: June 5, 2018
• First Submitted That Met QC Criteria: July 22, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Actual): July 31, 2018
• Last Update Submitted That Met QC Criteria: July 22, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Hematologic Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Liver Diseases; Hemorrhagic Disorders; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Colonic Diseases; Intestinal Diseases; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Gallbladder Diseases; Biliary Tract Diseases; Pancreatic Diseases; Biliary Tract Neoplasms; Glioblastoma; Multiple Myeloma; Neoplasms, Plasma Cell; Rectal Neoplasms; Pancreatic Neoplasms; Liver Neoplasms; Colonic Neoplasms; Gallbladder Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Anticonvulsants; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Gemcitabine; Temozolomide; Oxaliplatin; Bevacizumab; Leucovorin; Irinotecan; Bortezomib; Cannabidiol
• Other Study ID Numbers: Olympian

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No