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NCT Number: NCT02655601

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

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.

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Key information

Conditions

High Grade Glioma Astrocytoma Astrocytoma, Grade III Glioblastoma Glioma Neoplasms Neoplasms by Histologic Type Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neuroectodermal Tumors

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

University of Alabama- Birmingham, Birmingham, Alabama, United States

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About this study

160 patients will be enrolled and randomized with a treatment arm allocation ratio of 1:1 in the Phase 2 study. At enrollment, patients will be assessed with medical history, physical/neurological examinations, standard laboratory evaluations (CBC with differential and comprehensive metabolic panel (CMP)), baseline brain MRI with and without gadolinium, cognitive testing and patient-reported outcome questionnaires of HRQoL. On the first day of BMX-001 (loading dose), patients will be evaluated with medical history, patient physical/neurological examinations, and standard laboratory evaluations (CBC with differential and CMP), and ECG. Patients in Arm A will be administered BMX-001 subcutaneously first as a loading dose before the start of chemoradiation and then at maintenance dose (50% of the loading dose) twice a week for 8 weeks. Because oxidative stress continues to occur for up to several weeks following RT, the proposed protocol includes administering BMX-001 both before the start of RT and continuing for 2 weeks after the completion of RT and TMZ. TMZ will be dosed at 75 mg/m2 orally daily for 42 days and 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. During standard RT and TMZ, CBC with differential and CMP will be obtained weekly. Two weeks after the completion of standard RT and TMZ and every 8 weeks during adjuvant TMZ, patients will be evaluated with the following: medical history, physical/neurological examinations, Brain MRI with and without gadolinium, cognitive testing and patient-reported outcome questionnaires of HRQoL. 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. In light of the findings that BMX-001 can spare radiation-induced hair loss in a mouse model [41], we will evaluate and describe hair loss as an exploratory outcome in HGG patients by evaluating hair at baseline and then every 8 weeks. Patients will be discontinued from the study if they experience progression of disease, death or withdraw informed consent.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • 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
  • A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >480 milliseconds (ms) (CTCAE grade 1)
  • A known history of additional risk factors for Torsades de Pointes (TdP) (e.g., congestive heart failure, hypokalemia, known family history of Long QT Syndrome).

Treatment and study plan

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.

Other names: manganese butoxyethyl pyridyl porphyrin

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.

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.

Other names: TMZ

Primary outcomes

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

    Time frame: 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)

    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.

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

    Time frame: 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

    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.

Secondary outcomes

  1. Phase 1: Median Overall Survival

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

    Median Overall Survival (OS) is a key clinical outcome measure used to assess the efficacy of BMX-001 in combination with standard radiotherapy (RT) and temozolomide (TMZ) in patients with newly diagnosed high-grade gliomas (HGG). OS is defined as the time from the date of study enrollment to the date of death from any cause. Survival status was assessed at regular follow-up intervals (e.g., every 3 months post-treatment) through medical records, patient contact, and clinical evaluations. The final analysis was conducted after a pre-specified number of events (deaths) have occurred.

    Expected Outcome: Prolonged median OS compared to historical or control data (RT + TMZ alone) would suggest a survival benefit associated with BMX-001.

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

    Time frame: 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)

    This is only applicable for the Phase 1 portion of the study. All patients who received at least 1 dose of BMX-001, regardless of dose level, after enrolling on study are included in the analysis.

  3. 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).

    Time frame: 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)

    The Controlled Oral Word Association Test (COWAT) measures verbal fluency which reflects executive functioning, processing speed, mental flexibility, and language output.

    The raw score is then adjusted for age, education, and normative data to allow meaningful comparisons across individuals. The standardized score (T-score) is calculated using normative reference tables.

    Higher Scores = Better Cognitive Function, lower scores = cognitive impairment. T score range is 0-100.

    A T-score of 50 represents the mean performance in the normative population, this means a score of 50 indicates the population mean performance with a standard deviation of 10.

    T-scores below 40 suggest clinically significant cognitive decline. Scores range from < 30 (significantly below average), to 30-39 (below average), 40-59 (average), and greater than or equal to 60 is above average.

    Stable or improved COWAT scores over time would suggest that adding BMX-001 may help preserve cognitive function.

  4. 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

    Time frame: 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)

    Part A of the Trails Making Test (TMT) measures visual attention and processing speed by requiring the patient to connect numbers sequentially (1 → 2 → 3, etc.) as quickly as possible. This is a widely used neuropsychological test that measures visual attention, processing speed, and psychomotor function.

    Raw scores are measured in seconds (time to complete the task), but T-scores are derived by converting time-based results into a normed distribution accounting for age and education.

    Mean (SD) change in cognitive assessment in T-Scores is reported and the range is 0-100.

    T score interpretation and range is < 30 (significantly impaired), 30-39 (mildly impaired), 40-59 (Average), >/= 60 (Above average). A T-score of 50 represents the mean performance in the normative population, this means a score of 50 indicates the population mean performance with a standard deviation of 10.

    Higher scores = better performance.

  5. 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

    Time frame: 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)

    The Trails Making Test (TMT) Part B is a widely used neuropsychological test that measures set-shifting ability, processing speed, and working memory. While Part A focuses on speed, visual scanning, and attention.

    Prolonged completion time or an increase in errors compared to baseline or age-adjusted norms would indicate cognitive decline.

    Raw scores are measured in seconds (time to complete the task), but T-scores are derived by converting time-based results into a normed distribution accounting for age and education.

    Mean (SD) change in T score is reported, range is 0-100. T score interpretation and range is < 30 (significantly impaired), 30-39 (mildly impaired), 40-59 (Average), >/= 60 (Above average). A T-score of 50 represents the mean performance in the normative population, this means a score of 50 indicates the population mean performance with a standard deviation of 10.

    Higher scores = better performance.

  6. 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 Total Recall Change T-score Achieved on the Hopkins Verbal Learning Test- Revised (HVLT-R)

    Time frame: 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)

    Hopkins Verbal Learning Test- Revised (HVLT-R) is a standardized neuropsychological assessment that measures verbal learning and memory, including total (immediate recall). Total Recall T-score is derived from the sum of correctly recalled words across three learning trials and is normalized based on age-adjusted normative data. This provides insight into immediate verbal memory performance and learning ability.

    Total Recall (Immediate Memory & Learning) is Sum of correctly recalled words across three learning trials and is a measurement of immediate recall capacity and learning efficiency.

    Raw score range is 0-36, T score range is 0-100. T scores >/= 60 are above average and T scores < 40 are below average. A T-score of 50 represents the mean performance in the normative population, this means a score of 50 indicates the population mean with a standard deviation of 10

  7. Phase 2: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

    Time frame: Adverse events occurring from baseline through 30 days post completion of treatment (approximately 12 weeks total).

    To assess the safety and tolerability of standard RT and TMZ in combination with BMX-001 compared to standard RT and TMZ alone in newly diagnosed HGG patients. The phase 2 portion of this study has two adverse event endpoints:

    • The proportion of patients who experience any grade 3 or 4 adverse event during radiation and temozolomide treatment, and
    • The proportion of patients who experience a grade 3 or 4 adverse event that is definitely, possibly, or probably related to BMX-001 treatment during this same period.

    This outcome measure does not apply to the Phase 1 portion of the study, as it was not designated as an outcome for Phase 1 but was specified only for Phase 2.

  8. Phase 2: Incidence of Treatment-Emergent Adverse Events Related to BMX-001

    Time frame: Adverse events occurring from baseline through 30 days post completion of treatment (approximately 12 weeks total).

    To assess the safety and tolerability of standard RT and TMZ in combination with BMX-001 compared to standard RT and TMZ alone in newly diagnosed HGG patients.

    This outcome is measured to test the proportion of patients who experience a grade 3 or 4 adverse event that is definitely, possibly, or probably related to BMX-001 treatment during this same period.

    This outcome measure does not apply to the Phase 1 portion of the study, as it was not designated as an outcome for Phase 1 but was specified only for Phase 2. It also only applies to Arm A in the study as Arm B did not receive the study drug.

  9. Phase 2: Protection/Improvement of Cognition Using Hopkins Verbal Learning-Revised

    Time frame: Baseline and Week 24

    Hopkins Verbal Learning Test- Revised (HVLT-R) is a standardized neuropsychological test that measures verbal learning and memory, including total (immediate recall), delayed recall, and recognition discrimination. It is scored using a T-score which are calculated based on raw scores (e.g., number of words recalled) and standardized using normative data adjusted for age, education, and sometimes sex. T-score range is 0-100. T-scores >/= 60 are above average and T scores < 40 are below average. Higher scores are better. Total recall interpretation - T ≥ 60: above average; T < 40: below average. Delayed recall - T < 30 may suggest memory consolidation issues, and recognition discrimination - T < 30 may indicate impaired recognition memory. A T-score of 50 represents the mean performance in the normative population, this means a score of 50 indicates the population mean performance with a standard deviation of 10.

    Mean (SD) change in cognitive assessment is reported.

  10. Phase 2: Protection/Improvement of Cognition Via the Controlled Oral Word Association Test (COWAT)

    Time frame: Baseline and Week 24

    This Controlled Oral Word Association Test (COWAT) measure verbal fluency which reflects executive functioning, processing speed, mental flexibility, and language output.

    The raw score is adjusted for age, education, and normative data to allow meaningful comparisons across individuals. The standardized score (T-score) is calculated using normative reference tables.

    Higher Scores = Better Cognitive Function, lower scores = cognitive impairment. T-score range is 0-100 A T-score of 50 represents the mean performance in the normative population, this means a score of 50 indicates the population mean performance with a standard deviation of 10.

    T-scores below 40 suggest clinically significant cognitive decline. Scores range from < 30 (significantly below average), to 30-39 (below average), 40-59 (average), and greater than or equal to 60 is above average.

    Stable or improved COWAT scores over time would suggest that adding BMX-001 may help preserve cognition.

  11. Phase 2: Protection/Improvement of Cognition - Trails Making Test A and B

    Time frame: Baseline and Week 24 Baseline and Week 24 Baseline and Week 24

    Phase 1 is reported separately. Neurocognitive testing was done and reported here for the Trails Test A and B Part A: Visual attention and processing speed Part B: Executive functioning, task switching, and divided attention. Part A testing time is typically 20-90 sec, and Part B time is typically 40-180 sec.

    Raw scores are measured in seconds (time to complete the task), but T-scores are derived by converting time-based results into a normed distribution accounting for age and education.

    Mean (SD) change in cognitive assessment in T-Scores is reported T score interpretation and range is < 30 (significantly impaired), 30-39 (mildly impaired), 40-59 (Average), >/60 (above average) A T-score of 50 represents the mean performance in the normative population, this means a score of 50 indicates the population mean performance with a standard deviation of 10.

    Lower times = better

  12. Phase 2: Protection of Bone Marrow Against Chemotherapy-Induced Thrombocytopenia

    Time frame: Approximately 12 weeks (from Baseline to 30 days post completion of treatment)

    This was not a secondary outcome in Phase 1 and therefore only applies to Phase 2. The proportion of patients who experience grade 3 or 4 thrombocytopenia during concurrent temozolomide and radiation will be recorded within each treatment group. The proportion of patients who experience a platelet count less than 100K during concurrent temozolomide and radiation will also be recorded within each treatment group. For both endpoints described above, a chi-square or Fisher's exact test was conducted to compare the prevalence of such thrombocytopenia observed in patients with and without BMX-001.

  13. Phase 1 and Phase 2: Progression-free Survival (PFS)

    Time frame: up to 5 years

    The primary analysis of PFS will consider all patients, and consider them in their assigned treatment arm regardless of compliance. This approach to analysis is consistent with an intent-to-treat analysis approach. Progression-Free Survival (PFS) is defined as the time from randomization (Phase 2) or study enrollment (Phase 1) to the first occurrence of either disease progression (as determined by standardized radiographic criteria, the RANO [Response Assessment in Neuro-Oncology] criteria) or death from any cause, whichever occurs first. Patients who have not experienced progression or death at the time of analysis will be censored at their last known follow-up date. PFS will be estimated using the Kaplan-Meier method, providing median PFS and corresponding 95% confidence intervals (CI).

  14. Phase 1 and 2: Complete or Partial Radiographic Response to Tumor

    Time frame: 12 weeks

    The guidelines and criteria for radiographic response will be based on the updated RANO criteria for newly diagnosed GBM. MRI brain with and without contrast will be obtained at enrollment, 2-4 weeks after standard RT and TMZ, and every 8 weeks during adjuvant TMZ. Since this is a study in newly diagnosed patients with HGG, the baseline imaging will be designated as the imaging obtained 2 to 4 weeks after the completion of standard RT and TMZ. At each time point, based on RANO criteria, the subject response will be characterized as Complete Response, Partial Response, Progressive Disease, Stable Disease, or Not Evaluable.

Sponsors and collaborators

Lead sponsor

BioMimetix JV, LLC

Industry

Collaborators

  • Duke Cancer Institute
  • National Cancer Institute (NCI)

Registry information

Official study title

A Phase 2 Trial for Patients With Newly Diagnosed High Grade Glioma Treated With Concurrent Radiation Therapy, Temozolomide, and BMX-001

Acronym: BMX-HGG

Important dates

Study start
2018
Primary completion
2023
Study completion
2024
First posted
Jan 14, 2016
Registry last updated
Jun 8, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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