Clinical trial NCT04752813: A Study of BPM31510 With Vitamin K1 in Subjects With Newly Diagnosed Glioblastoma (GB)
Official title: A Study of BPM31510 With Vitamin K1 in Subjects With Newly Diagnosed Glioblastoma (GB)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Glioblastoma
Glioblastoma Multiforme
Lead sponsor: BPGbio
Sponsor class: INDUSTRY
First posted: 2021-02-12
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-arm, non-randomized, open-label Phase 2 therapeutic study that will assess the effects of adding BPM31510 onto a conventional treatment framework of RT and concurrent TMZ chemotherapy for subjects with newly diagnosed glioblastoma.

Detailed description: The study will start with a dose-confirmation phase to establish safety of BPM31510 in combination with RT and TMZ. This phase will follow a standard 3+3 dose design with the starting dose of BPM31510 at 110 mg/kg/week (wk), with 1 potential dose de-escalation to 66 mg/kg/wk in the event a DLT is experienced at the 110 mg/kg dose. Toxicity at this dose level will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (CTCAE v5). Subjects will be monitored for DLTs associated with combination therapy for 30 days (d) (± 5 d) after the end of RT (DLT assessment period). Subjects will continue to be monitored for late radiation-related DLTs during follow up, every 8 wk (± 2 wk) during the first 12 months (mo), and then every 12 wk (± 2 wk) for a total of 5 years (y). Safety oversight will be provided by the independent Data and Safety Monitoring Committee (DSMC). The DSMC will review and confirm all DLT data, make recommendations for dose modifications, if necessary, and continue to monitor safety throughout the study. The efficacy phase of the study will begin after the recommended Phase 2 dose (RP2D) has been confirmed.

Eligibility criteria: Inclusion Criteria:

1. Subjects with newly diagnosed pathologically verified GB.
2. No prior RT, chemotherapy, immunotherapy, or targeted agents administered specifically for the lesion being treated.
3. Age ≥18 y.
4. Life expectancy ≥3 months.
5. Karnofsky performance score ≥60.
6. Adequate organ and marrow function as per protocol.
7. Ability for subject to understand and the willingness to sign a written ICF.
8. Subjects of childbearing potential must agree to use hormonal or barrier birth control with spermicidal gel to avoid pregnancy during the study.
9. Be at least 14 d out from surgery.

Exclusion Criteria:

1. No evidence of residual tumor.
2. History of clinically significant tumor-related cerebral hemorrhage.
3. Any serious cardiac history as per protocol.
4. Uncontrolled or severe coagulopathies or a history of clinically significant bleeding within the past 6 months.
5. Known predisposition for bleeding such as von Willebrand's disease or other such condition(s).
6. Uncontrolled concurrent illness.
7. Prior malignancy except for non-melanoma skin cancer and carcinoma in situ (of the cervix or bladder), unless diagnosed and definitively treated more than 3 y prior to first dose of study drug.
8. Receiving any of the following medications:

   1. Therapeutic doses of any anticoagulant, including low-molecular weight heparin. Concomitant use of warfarin, even at prophylactic doses, is prohibited.
   2. Digoxin, digitoxin, lanatoside C, or any type of digitalis alkaloids.
   3. Antiangiogenic drugs (ie, Avastin) either in the past 2 wk or if anticipated within the next 2 wk of informed consent.
   4. Theophylline
9. Known allergy to CoQ10.
10. Known allergy or adverse reaction to oral, subcutaneous, or IV Vitamin K1.
11. Pregnant or lactating.
12. Known to be positive for the human immunodeficiency virus (HIV). Note: HIV testing is not required for eligibility, but if performed previously and was positive, the subject is ineligible.

Primary outcomes:
measure: Efficacy will be assessed by subject progression free survival
timeFrame: 6 months
Secondary outcomes:
measure: Efficacy will be assessed by subject Overall survival
timeFrame: 5 years
measure: Safety and tolerability of BPM31510 and Vitamin K1 will be assessed by incidence of dose limiting toxicities (DLTs) and adverse events (AEs).
timeFrame: 28 days post treatment
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Palo Alto
country: United States
facility: Stanford University Cancer Center
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ridgewood
country: United States
facility: Valley Health
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Austin
country: United States
facility: Texas Oncology
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio Mays Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Fairfax
country: United States
facility: Inova
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
References: