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

NCT03687034 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: Olympian 2
• Study Type: interventional
• Target: 21
• Locations: 0 countries
• Sites: N/A

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

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  The primary objective of this study is to evaluate the safety and tolerability of BRCX014 using clinical assessments and lab results.

  Through study completion, an average of one year

Secondary Outcomes (3)

• Maximum tolerated dose

  Through study completion, an average of one year

• Levels of metabolites

  Through study completion, an average of one year

• Progression-free survival

  Through study completion, an average of one year

Study Arms (1)

BRCX014

EXPERIMENTAL

Subjects will receive escalating doses of BRCX014 in conjunction with standard-of-care (SOC) treatment. For patients with GBM, following standard chemo-radiation treatment (radiation: 2 Gy per day for a total of 60 Gy; and temozolomide: 75 mg per square meter of body-surface area per day, seven days per week from the first to the last day of radiotherapy), SOC treatment comprises six cycles of adjuvant temozolomide (150 to 200 mg per square meter for five days during each 28-day cycle), with or without use of alternating electric field therapy (Optune device).

Drug: Temozolomide; Device: Optune

Interventions

Temozolomide DRUG

Standard-of-care chemotherapy for patients with glioblastoma 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, seven 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 five days during each 28-day cycle).

Also known as: Temodar

BRCX014

Optune DEVICE

Standard-of-care treatment for glioblastoma includes alternating electric-field therapy, or Optune, as a Category 1 treatment in conjunction with temozolomide after maximal safe resection and completion of radiation therapy.

Also known as: TTFields

BRCX014

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Leaf Vertical Inc.: lead

MeSH Terms

Conditions

Glioblastoma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Nicholas Avgeropoulos, MD

  Orlando Health / UF Health Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Philip A Arlen, PhD

CONTACT

4074430656; parlen@leafvertical.com

William Fisher

CONTACT

407-797-2332; ceo@leafvertical.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: September 27, 2018
• Study Start: June 1, 2019
• Primary Completion: September 30, 2019
• Study Completion: December 31, 2020
• Last Updated: February 26, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share