Trial of Newly Diagnosed High Grade Glioma Treated With Concurrent Radiation Therapy, Temozolomide and BMX-001

NCT02655601 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: BMX-HGG-001
• Study Type: interventional
• Target: 177
• Locations: 1 country
• Sites: 9

Brief Summary

This is a Phase 2 study of newly diagnosed patients with high grade glioma (HGG) undergoing standard radiation therapy and temozolomide treatment. BMX-001 added to radiation therapy and temozolomide has the potential not only to benefit the survival of high grade glioma patients but also to protect against deterioration of cognition and impairment of quality of life. BMX-001 will be given subcutaneously first with a loading dose zero to four days prior to the start of chemoradiation and followed by twice a week doses at one-half of the loading dose for the duration of radiation therapy plus two weeks. Both safety and efficacy of BMX-001 will be evaluated. Impact on cognition will also be assessed. Eighty patients will be randomized to the treatment arm that will receive BMX-001 while undergoing chemoradiation and 80 patients randomized to receive chemoradiation alone. The sponsor hypothesizes that BMX-001 when added to standard radiation therapy and temozolomide will be safe at pharmacologically relevant doses in patients with newly diagnosed high grade glioma. The sponsor also hypothesizes that the addition of BMX-001 will positively impact the overall survival and improve objective measures of cognition in newly diagnosed high grade glioma patients.

Conditions

High Grade Glioma; Astrocytoma, Grade III; Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Phase 1: Maximum Tolerated Dose (MTD) of BMX-001 Administered in Combination With Standard RT and TMZ in Newly Diagnosed HGG Patients

  This was a dose escalation study in which patients were enrolled to receive 1 of 4 doses in dose ascending order. MTD was defined as the dose level that has an estimated DLT rate nearest to 0.25. This is applicable to the Phase 1 part of the study only. Note that an actual MTD was not reached, however a Phase 2 recommended dose was selected based on the dose that was most tolerable to patients.

  From the time the subject signs the informed consent form through 30 days after completion of the final BMX-001 treatment (up to approximately 16 weeks)

• Phase 2: Overall Survival, Intent to Treat (ITT) Population

  This is applicable for Phase 2 only. It was a secondary objective of Phase 1 and that is reported as a separate outcome measure. Assessment of overall survival. With standard treatment, the median survival of Grade IV patients is expected to be 14.6 months, and the median survival of Grade III is approximately 36 months. Given that we anticipate that approximately 10% of patients to be Grade III, we estimate that the overall median survival with standard treatment to be roughly 16.7 months.

  From the time between randomization and death, or the date of last follow-up if the patient remains alive. Per protocol, patients will be followed indefinitely

Secondary Outcomes (14)

• Phase 1: Median Overall Survival

  From the time between enrollment and death, or the date of last follow-up if the patient remains alive.

• Phase 1: Number of Participants Who Experiences a Dose-limiting Toxicity (DLT).

  From the time the subject signs the informed consent form through 30 days after completion of the final BMX-001 treatment (up to approximately 16 weeks)

• Phase 1: Examine the Impact on Cognition of BMX-001 in Combination With Standard RT and TMZ in Treatment of Newly Diagnosed HGG Patients Via the Adjusted Change T Score Achieved on the Controlled Oral Word Association Test (COWAT).

  From the time the subject signs the informed consent form through 6 months after completion of the final BMX-001 treatment (up to approximately 40 weeks)

• Phase 1: Examine the Impact on Cognition of BMX-001 in Combination With Standard RT and TMZ in Treatment of Newly Diagnosed HGG Patients Via the Normalized Score Achieved on the Trails Making Test (TMT): Part A

  From the time the subject signs the informed consent form through 6 months after completion of the final BMX-001 treatment (up to approximately 40 weeks)

• Phase 1: Examine the Impact on Cognition of BMX-001 in Combination With Standard RT and TMZ in Treatment of Newly Diagnosed HGG Patients Via the Normalized Score Achieved on the Trail Making Test (TMT): Part B

  From the time the subject signs the informed consent form through 6 months after completion of the final BMX-001 treatment (up to approximately 40 weeks)

Study Arms (3)

Phase 2 Arm A: Radiation Therapy, TMZ and BMX-001

EXPERIMENTAL

Patients will receive standard of care radiation therapy plus temozolomide (TMZ). BMX-001 will be given by subcutaneous injection with a loading dose of 28 mg/subject given within 4 days prior to initiation of radiation therapy and followed by biweekly maintenance doses at half the loading dose for a total of 8 weeks. A total of 80 subjects will receive BMX-001 in this phase.

Drug: BMX-001; Radiation: Radiation Therapy; Drug: Temozolomide

Phase 2 Arm B: Radiation Therapy and TMZ

ACTIVE COMPARATOR

In this arm, one-half of the study subjects will not receive BMX-001 but will undergo all components of standard therapy (radiation therapy plus temozolomide \[TMZ\]). A total of 80 subjects will be in this study arm.

Radiation: Radiation Therapy; Drug: Temozolomide

Phase 1

EXPERIMENTAL

All subjects enrolled will receive BMX-001 at one of 4 different dose levels. BMX-001 will be given by subcutaneous injection with a loading dose given within 4 days prior to initiation of radiation therapy and followed by biweekly maintenance doses (half the dosing dose) for a total of 8 weeks. Subjects will also undergo standard therapy (radiation therapy plus temozolomide \[TMZ\])

Drug: BMX-001; Radiation: Radiation Therapy; Drug: Temozolomide

Interventions

BMX-001 DRUG

BMX-001 consists of a porphyrin ring with pyridyl groups attached at each of the four methane bridge carbons. The nitrogen in the pyridyl ring is at the 2 position and has a side chain consisting of six carbons with an ether linkage. A manganese atom is chelated into the porphyrin ring and is the active center of the molecule. This molecule is an enzymatic scavenger of free radical species operating at close to diffusion-limited rates.

Also known as: manganese butoxyethyl pyridyl porphyrin

Phase 1; Phase 2 Arm A: Radiation Therapy, TMZ and BMX-001

Radiation Therapy RADIATION

RT will be delivered in daily fractions of 1.8-2 Gy given 5 days a week for 6 weeks for a total of 59.4-60 Gy.

Phase 1; Phase 2 Arm A: Radiation Therapy, TMZ and BMX-001; Phase 2 Arm B: Radiation Therapy and TMZ

Temozolomide DRUG

Initially, temozolomide (TMZ) will be dosed at 75 mg/m2 orally daily for 42 days. Two weeks after the completion of chemoradiation, patients will transition to adjuvant chemotherapy with TMZ dosed at 150-200 mg/m2 orally for 5 days of a 28-day cycle for a total of 12 cycles.

Also known as: TMZ

Phase 1; Phase 2 Arm A: Radiation Therapy, TMZ and BMX-001; Phase 2 Arm B: Radiation Therapy and TMZ

Eligibility Criteria

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

You may qualify if:

• Subjects must have histologically confirmed diagnosis of World Health Organization (WHO) grade III or IV malignant glioma
• Subjects must be planning to start standard of care radiation therapy and chemotherapy
• Subjects must be within 12 weeks of last major neurosurgical procedure for the high-grade glioma (craniotomy, open biopsy, or stereotactic biopsy)
• Subjects must have had a definitive resection with residual radiographic contrast enhancement on post-resection CT or MRI of less than or equal to 3 cm in any two perpendicular planes on any images
• Age \* 18 years
• Karnofsky Performance Status (KPS) ≥ 70%
• Hemoglobin ≥ 9.0 g/dl, absolute neutrophil count (ANC) ≥ 1,500 cells/µl, platelets ≥ 125,000 cells/µl
• Serum creatinine ≤ 1.5 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) and bilirubin ≤ 1.5 times upper limit of normal
• Signed informed consent approved by the Institutional Review Board
• If sexually active, patients must agree to use appropriate contraceptive measures for the duration of the study and for 12 months afterwards as stated in the informed consent
• Stable and/or decreasing dose of corticosteroids for greater than or equal to 7 days.

You may not qualify if:

• Pregnancy or breast-feeding
• Active infection requiring IV antibiotics 7 days before enrollment
• Signs of wound-healing problems or infection at the craniotomy/biopsy site.
• Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
• Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids
• Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of the grade of the tumor
• Evidence of \> grade 1 CNS hemorrhage on baseline MRI on CT scan
• Systemic treatment with inducers or strong inhibitors of cytochrome P450 within four days before enrollment or planned treatment during the time period of the study.
• Metal in the body (except dental fillings) e.g., pacemaker, infusion pump, metal aneurysm clip, metal prosthesis, joint, rod or plate.
• Severe allergy to contrast agent.
• Inadequately controlled hypertension
• Active or history of postural hypotension and autonomic dysfunction
• Clinically significant (i.e. active) cardiovascular disease or cerebrovascular disease, for example cerebrovascular accidents ≤ 6 months prior to study enrollment, myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment
• History or evidence upon physical/neurological examination of central nervous system disease (e.g. seizures) unrelated to cancer unless adequately controlled by medication or potentially interfering with protocol treatment
• Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to start of study treatment

Sponsors & Collaborators

• BioMimetix JV, LLC: lead
• Duke Cancer Institute: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (9)

University of Alabama- Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

St. Luke's Hospital

Kansas City, Missouri, 64111, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (3)

• Jones LW, Cohen RR, Mabe SK, West MJ, Desjardins A, Vredenburgh JJ, Friedman AH, Reardon DA, Waner E, Friedman HS. Assessment of physical functioning in recurrent glioma: preliminary comparison of performance status to functional capacity testing. J Neurooncol. 2009 Aug;94(1):79-85. doi: 10.1007/s11060-009-9803-x. Epub 2009 Feb 11.

  PMID: 19212703 BACKGROUND

• Moulder JE, Cohen EP. Future strategies for mitigation and treatment of chronic radiation-induced normal tissue injury. Semin Radiat Oncol. 2007 Apr;17(2):141-8. doi: 10.1016/j.semradonc.2006.11.010.

  PMID: 17395044 BACKGROUND

• Gad SC, Sullivan DW Jr, Spasojevic I, Mujer CV, Spainhour CB, Crapo JD. Nonclinical Safety and Toxicokinetics of MnTnBuOE-2-PyP5+ (BMX-001). Int J Toxicol. 2016 Jul;35(4):438-53. doi: 10.1177/1091581816642766. Epub 2016 Apr 20.

  PMID: 27098749 DERIVED

MeSH Terms

Conditions

Glioma; Astrocytoma; Glioblastoma

Interventions

Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin; Radiotherapy; Temozolomide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Sara Penchev
• Organization: BioMimetix JV, LLC

sara.penchev@bmxpharma.com

610-308-6640

Study Officials

• Katherine Peters, MD, PhD

  Duke Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Phase 1 - Single Arm Phase 2- Randomized
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: There is 1 arm of subjects enrolled in Phase 1 (all subjects receiving the study drug + SOC). In Phase 2, subjects are enrolled in two arms (Arm A: SOC + BMX-001 and Arm B: SOC alone)

Study Record Dates

• First Submitted: January 12, 2016
• First Posted: January 14, 2016
• Study Start: September 25, 2018
• Primary Completion: August 17, 2023
• Study Completion: December 31, 2024
• Last Updated: June 8, 2025
• Results First Posted: June 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)