A Study of BPM31510 With Vitamin K1 in Subjects With Newly Diagnosed Glioblastoma (GB)

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.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma; Glioblastoma Multiforme
• Intervention / Treatment: Drug: BPM31510; Other: Vitamin K1; Drug: Temozolomide (TMZ); Radiation: Radiation

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Vijay Modur, MD, PhD; Phone Number: 617-588-0083; Email: clinicaltrials.connect@berghealth.com
• Study Contact Backup: Name: Arianne Lyng; Phone Number: 508-988-0273; Email: clinicaltrials.connect@berghealth.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
      • Contact: Chirag Patil, MD,MS; Email: clinicaltrials.connect@berghealth.com
    • Palo Alto, California, United States, 94305
      • Recruiting
      • Stanford University Cancer Center
      • Contact: Seema Nagpal, MD; Email: clinicaltrials.connect@berghealth.com
    • Santa Monica, California, United States, 90403
      • Withdrawn
      • Sarcoma Oncology Research Center
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai Hospital
      • Contact: Rebecca M Brown, MD,PhD; Email: clinicaltrials.connect@berghealth.com
  • Virginia
    • Fairfax, Virginia, United States, 22037
      • Recruiting
      • Inova
      • Contact: Adam Cohen, MD; Email: clinicaltrials.connect@berghealth.com
  • Washington
    • Seattle, Washington, United States, 98101
      • Not yet recruiting
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BPM31510, Vitamin K1, RT and TMZ; Subjects will receive a BPM31510 96hr infusion once weekly for 8 wk. Prophylactic Vitamin K1 at a recommended dose of 10 mg will be given intramuscular (IM) to all subjects prior to the beginning of each week of therapy. After 2 wk of treatment with BPM31510, subjects will start concurrent standard RT and TMZ 75 mg/m2 once daily (qd) × 42 days. Subjects will receive the standard TMZ treatment for additional 6 cycles post BPM31510 treatment.

Drug: BPM31510; Subjects will receive a weekly, 96-h infusion of BPM31510 for a duration of 8 weeks.; Other: Vitamin K1; Subjects will receive prophylactic Vitamin K1 at a recommended dose of 10 mg Intramuscularly prior to the beginning of each week of BPM31510 therapy.; Drug: Temozolomide (TMZ); After 2 wk of treatment with BPM31510 (ie, on Day 15), subjects will start concurrent TMZ 75 mg/m2 once daily (qd) × 42 days. Subjects will receive the standard TMZ treatment for additional 6 cycles post BPM31510 treatment.; Radiation: Radiation; After 2 wk of treatment with BPM31510 (ie, on Day 15), subjects will start concurrent standard RT for 42 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy will be assessed by subject progression free survival	Progression free survival will be determined by measuring the proportion of subjects who have met RANO criteria for complete response, partial response , or stable disease at 6 mo following initiation of BPM31510.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy will be assessed by subject Overall survival	Overall survival as determined by measuring from start date of BPM31510 to the date of death or date of last follow-up (for subjects who have not died).	5 years
Safety and tolerability of BPM31510 and Vitamin K1 will be assessed by incidence of dose limiting toxicities (DLTs) and adverse events (AEs).	A DLT is defined as an event possibly related to BPM31510 and clearly not due to an underlying disease or extraneous causes. An AE is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.	28 days post treatment

Collaborators and Investigators

• Sponsor: Berg, LLC
• Collaborators: BPGbio

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2022
• Primary Completion (Estimated): February 24, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: February 1, 2021
• First Submitted That Met QC Criteria: February 11, 2021
• First Posted (Actual): February 12, 2021

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Micronutrients; Vitamins; Antifibrinolytic Agents; Hemostatics; Coagulants; Temozolomide; Vitamin K; Vitamin K 1
• Other Study ID Numbers: BPM31510IV-11

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No