Studying the Safety, Efficacy, and Pharmacokinetic Characteristics of BNCT in Patients With Recurrent High-grade Gliomas

NCT05737212 | Terminated Phase 1 DMC

• 1 other identifier: DM-BNCT-P001
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-centered, radiation dose escalation, open, exploratory, Phase 1/2a clinical trial on the safety, efficacy and pharmacokinetic characteristics of BNCT in patients with recurrent high-grade gliomas. The Phase I clinical study is to explore the adequate radiation dose level of BNCT based on confirmation of the maximum tolerated dose (radiation dose) of BNCT in patients with recurrent high-grade gliomas and characterize the safety, efficacy and pharmacokinetics. To evaluate the primary objective of tolerability, subject population with history of exposure to a similar treatment recurrent high-grade glioma who received prior standard radiotherapy will be recruited. The Phase IIa is to confirm the efficacy and safety after irradiation of radiation dose confirmed in the Phase I clinical study. To evaluate the primary objective of efficacy, subject population with glioblastoma (The 2021 WHO Classification of Tumors of the Central Nervous System, Glioblastoma IDH-wild type, WHO Grade 4) will be recruited.

Conditions

Recurrent High-grade Glioma; Recurrent Glioblastoma; Recurrent Anaplastic Astrocytoma; Recurrent Anaplastic Oligodendroglioma

Keywords

Boron neutron capture therapy; boronophenylalanine; neutron capture therapy

Outcome Measures

Primary Outcomes (2)

• Phase I: To explore the adequate radiation dose level of BNCT based on confirmation of the maximum tolerated dose of BNCT

  To explore the adequate radiation dose level of BNCT based on confirmation of the maximum tolerated dose (radiation dose) of BNCT in patients with recurrent high-grade gliomas

  During 90 days post-BNCT

• Phase IIa: Proportion of 6-month PFS evaluated by central imaging according to the modified RANO criteria

  Percentage of patients that are free from progressive disease for 6 months per modified RANO criteria

  6 months

Secondary Outcomes (19)

• Proportion of 6-month PFS evaluated by central imaging according to the RANO criteria

  Up to 6 months

• Proportion of 6-month PFS evaluated by the investigator according to the modified RANO criteria

  Up to 6 months

• Median PFS evaluated by central imaging according to the modified RANO criteria

  Up to 6 months

• Median PFS evaluated by central imaging according to the RANO criteria

  Up to 6 months

• Median PFS evaluated by the investigator according to the modified RANO criteria

  Up to 6 months

Study Arms (3)

Group 1

EXPERIMENTAL

Radiation dose: 9 Gy-Eq * Investigational product, boronophenylalanine, DMX-101 500mg/kg/3hr * Investigational Device, DM-BTPS, DM-BNCT - neutron irradiation to reach maximum BNCT dose in brain of 9 Gy-Eq

Radiation: 500mg/kg/3hr followed by neutron irradiation to reach maximum brain dose of 9Gy-Eq

Group 2

EXPERIMENTAL

Radiation dose: 11 Gy-Eq * Investigational product, boronophenylalanine, DMX-101 500mg/kg/3hr * Investigational Device, DM-BTPS, DM-BNCT - neutron irradiation to reach maximum BNCT dose in brain of 11 Gy-Eq

Radiation: 500mg/kg/3hr followed by neutron irradiation to reach maximum brain dose of 11Gy-Eq

Group 3

EXPERIMENTAL

Radiation dose: 13 Gy-Eq * Investigational product, boronophenylalanine, DMX-101 500mg/kg/3hr * Investigational Device, DM-BTPS, DM-BNCT - neutron irradiation to reach maximum BNCT dose in brain of 13Gy-Eq

Radiation: 500mg/kg/3hr followed by neutron irradiation to reach maximum brain dose of 13Gy-Eq

Interventions

500mg/kg/3hr followed by neutron irradiation to reach maximum brain dose of 9Gy-Eq RADIATION

Patients will be infused DMX-101 intravenously at a dose of 500mg/kg/hr over 3 hours. Thereafter, patient will receive neutron irradiation simultaneously for a certain period of time based on his Boronophenylalanine (BPA) concentration in the blood.

Group 1

500mg/kg/3hr followed by neutron irradiation to reach maximum brain dose of 11Gy-Eq RADIATION

Patients will be infused DMX-101 intravenously at a dose of 500mg/kg/hr over 3 hours. Thereafter, patient will receive neutron irradiation simultaneously for a certain period of time based on his Boronophenylalanine (BPA) concentration in the blood.

Group 2

500mg/kg/3hr followed by neutron irradiation to reach maximum brain dose of 13Gy-Eq RADIATION

Patients will be infused DMX-101 intravenously at a dose of 500mg/kg/hr over 3 hours. Thereafter, patient will receive neutron irradiation simultaneously for a certain period of time based on his Boronophenylalanine (BPA) concentration in the blood.

Group 3

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• An adult at the age 19 or above to under 80 at the time of written consent
• Individual diagnosed with the following according to the WHO classification (2021)
• Astrocytoma, IDH-mutant, WHO grade 3, 4
• Oligodendroglioma, IDH-mutant, and 1p/19q-codeleted, WHO grade 3
• Glioblastoma, IDH wildtype, WHO grade 4
• Anaplastic Astrocytoma, NOS, WHO grade 3
• Anaplastic Oligoastrocytoma, NOS, WHO grade 3
• Anaplastic Oligodendroglioma, NOS, WHO grade 3
• Glioblastoma, NOS, WHO grade 4
• Individual who received radiation therapy at the standard level (54 to 66 Gy/25 to 35 fractions) or lower
• Individual confirmed to have disease progression\* according to the RANO criteria within 4 weeks from the screening visit (\*) At least one lesion with contrast enhancement needs to exist on the contrast enhancement MRI. For a subject who shows no lesion with contrast enhancement, functional imaging such as 18F-FET or 18F-FDOPA PET/CT needs to confirm the existence of at least one clear recurrent lesion.
• However, in the event differentiation between recurrence and pseudoprogression is unclear, the subject cannot participate in the screening
• Individual who is able to lie or sit for 30 minutes to 1 hour using the fixing device of the treatment couch
• Individual with no metal implant such as a pacemaker
• Individual with KPS (Karnofsky performance score) ≥ 60

You may not qualify if:

• Individual to which a traditional therapy such as reoperation or reirradiation is effectively applicable based on consultation with a brain tumor multidisciplinary committee or consultation among two or more medical departments, including neurosurgery and radiation oncology
• Individual who received cytotoxic anticancer therapy within 4 weeks from the screening visit (including previous interstitial anticancer therapy, local medication, and convection-enhanced delivery)
• Individual who received targeted anticancer therapy (e.g., bevacizumab) within 6 weeks from the screening visit
• Individual who received radiotherapy within 6 months from the screening visit
• Individual who received a radical surgery for high-grade glioma within 4 weeks from the screening visit
• Individual who received biopsy within 1 week from the screening visit
• Individual confirmed to have a history of the following:
• Interstitial brachytherapy
• Stereotactic radiosurgery
• Reirradiation for a recurrent lesion
• Cancer immunotherapy
• Individual with uncontrollable brain edema\* even with the use of corticosteroid (\*) Uncontrollable brain edema: Uncontrolled serious headache, vomiting, dyspnea, consciousness disturbance of NCI CTCAE (Ver. 5.0) grade 3 or above. However, for a patient taking corticosteroid, the patient must at least be on a stable dose or dose reduction for 7 days prior to the MRI scan at the screening visit.
• Individual confirmed with meningeal dissemination
• Individual diagnosed with cancer in another site\* in the past at the time of the screening visit and whose disease-free period is less than 3 years (\*) Patients with the skin basal cell carcinoma and carcinoma in situ of uterine cervix who received radical treatment are excluded
• Individual with hypotonic dehydration or hereditary fructose intolerance

Sponsors & Collaborators

• Dawonmedax Co., Ltd.: lead

Study Sites (1)

Gachon University Gil Medical Center

Incheon, South Korea

Location

MeSH Terms

Conditions

Glioma; Glioblastoma; Astrocytoma; Oligodendroglioma

Condition Hierarchy (Ancestors)

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

Study Officials

• Woo Kim, M.D., Ph.D.

  Dawonmedax Co., Ltd.

  STUDY DIRECTOR

Study Design

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

Model Details: In the Phase I clinical study, the 3+3 dose escalation design is applied to evaluate the dose limiting toxicity (DLT) and 3 study subjects are enrolled to each group (Group 1, Group 2, Group 3). Depending on whether or not DLT occurs, 3 subjects at minimum to 18 subjects at maximum are enrolled. However, in the event a subject assigned a subject number withdraws from the study before starting BNCT or within 90 days from starting BNCT for reasons other than safety, up to 3 additional subjects can be enrolled for each dose group, resulting in 27 subjects at maximum allowed for enrollment for the Phase I clinical study. In the Phase IIa clinical study, up to 12 subjects are enrolled. However, subjects who are included in a group that has received the radiation dose confirmed as the maximum tolerated dose (MTD) in the Phase 1 clinical study AND satisfy all inclusion/exclusion criteria of the Phase IIa are included in the number of subjects of Phase IIa.

Study Record Dates

• First Submitted: February 9, 2023
• First Posted: February 21, 2023
• Study Start: December 5, 2022
• Primary Completion: June 11, 2024
• Study Completion: June 11, 2024
• Last Updated: February 21, 2025

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)