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NCT Number: NCT07674095

Assessment of a Large US EHR Database as Meeting FDA Fit-for-Purpose Requirements to Provide External Controls for Study BPM31510 in Participants With Glioblastoma

Glioblastoma is a rare, aggressive brain tumor that leads to death within 2 years of diagnosis in more than half of patients. There are currently 123 studies ongoing that are testing treatments for glioblastoma. BPGbio has developed BPM31510 and is executing an ongoing single-arm Phase 2 study (NCT04752813) targeting 50 participants.

Because glioblastoma is a rare and often fatal disease with multiple drugs in development, a randomized placebo-controlled trial is unlikely to be feasible. Therefore, BPGbio is exploring the possible use of untreated patients from the Truveta database to create a control group. The purpose of this study is to explore whether the Truveta database in this indication meets FDA criteria as fit-for-purpose for regulatory use.

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Key information

Conditions

Glioblastoma Astrocytoma 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

Observational

Primary location

BPGbio

Waltham, Massachusetts, 02451, United States

About this study

This is a retrospective, observational cohort study to assess the degree to which the Truveta dataset meets the United States (US) Food and Drug Administration (FDA) fit-for-purpose requirements for label-enabling regulatory use as an external/synthetic control arm for the single-arm Phase 2 trial BPM31510IV-11 for the study of BPM31510 in subjects with newly diagnosed glioblastoma.

Glioblastoma is a rare disease with approximately 11,000 newly diagnosed cases in the US annually. The application of standard clinical trial eligibility criteria plus the requirement of no prior treatment (radiotherapy, chemotherapy, immunotherapy or targeted agents) in an environment of multiple ongoing Phase 2 and Phase 3 trials in this indication will make recruitment for a randomized, double-blind placebo-controlled trial infeasible. This is likely a core contributor to the lack of new glioblastoma treatments since the approval of temozolomide for newly diagnosed glioblastoma in 2005. Recently, the FDA approved dordaviprone for second-line treatment of diffuse midline glioma with an H3 K27M mutation based on a series of single arm studies with a total of 50 treated participants.

The addition of an external/synthetic control arm to the single-arm, non-randomized, open-label Phase 2 trial (BPM31510IV-11) will provide adequate and well-controlled data demonstrating substantial evidence of effectiveness to serve as the primary basis for approval for BPM31510.

The scientific integrity of this study is dependent on demonstrating that the proposed real-world Truveta database meets FDA requirements for real-world data for label-enabling regulatory submission.

Who can participate

Healthy volunteers accepted: No

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

Cohort 1 inclusion Criteria:

  • Between 01-01-2021 and 06-30-2025, an ICD-10-CM code C71.X (malignant brain neoplasm) and/or SNOMED CT 276826005 (malignant glioma of brain)
  • Between 01-01-2021 and 06-30-2025, current procedural terminology (CPT) codes indicating surgery with either a biopsy or excision of a brain tumor
  • Patients must be adults at least 18 years of age at time of surgery
  • CPT codes indicating submission of surgical sample for pathology for IDH testing
  • SNOMED CT codes for "glioblastoma" after IDH testing
  • Note that while a diagnosis can be made based on IDH from a biopsy or resection sample, resection is required for study inclusion.
  • A post-resection CPT code for brain MRI
  • At least one visit meeting all eligibility criteria between 15- and 50-days post-resection.

Cohort 1 exclusion Criteria:

  • History of malignant neoplasm of the brain >12 months before index
  • Patients with prior chemotherapy, radiotherapy, immunotherapy or targeted treatment agents (including anti-angiogenic drugs) less than 12 months before and/or 14 days after resection.

Cohort 2 inclusion Criteria:

Patients must meet all eligibility criteria for Cohort 1 and the following:

  • Brain MRI scan post-resection available for evaluation
  • Karnofsky performance score of at least 60
  • Laboratory values within the following specified ranges:
  • Absolute neutrophil count of at least 1.5 k/microliter (μL)
  • Platelet count of at least 100 k/μL
  • Hemoglobin level of at least 9 gram/deciliter (dL)
  • Serum creatinine level of at most 1.8 milligram(mg)/dL or creatinine clearance of more than 50 milliliter/min
  • Bilirubin level of at least 1.5 mg/dL
  • ALT level of at most 3.0 × upper limit of normal (ULN)
  • AST of at most 3.0 × ULN
  • PT of at most 1.5 × ULN
  • INR of at most 1.5 × ULN
  • PTT of at most 1.5 × ULN

Cohort 2 exclusion Criteria:

  • No resection was performed
  • One-year pre-index history of spontaneous or tumor-related intracranial hemorrhage
  • One-year pre-index history of diffuse leptomeningeal disease
  • Patients on dexamethasone daily dosing more than 2 mg at index
  • Three-month pre-index history of cardiovascular disease (myocardial infarction, coronary artery disease, arrhythmia, unstable angina pectoris, cerebrovascular accident)
  • Six-month pre-index history of acquired coagulopathies (hemorrhagic disorder due to circulating anticoagulants or acquired coagulation factor deficiency)
  • Six-month pre-index history of clinically significant bleeding
  • Known predisposition for bleeding such as von Willebrand's disease or other such condition(s) (i.e., hereditary deficiency of factor VIII, IX and XI)
  • Six-month pre-index history of significant psychiatric illness
  • Six-month pre-index history of major infection
  • Prior malignancy except for non-melanoma skin cancer and carcinoma in situ of the cervix or bladder
  • Receiving any of the following medications at the index date:
  • Any anticoagulant, including low-molecular weight heparin and warfarin within two months pre-index
  • Any digitalis alkaloid (digoxin, digitoxin, lanatoside C) within two months pre-index
  • Antiangiogenic drugs (e.g., bevacizumab) two weeks before or two weeks after index
  • Theophylline two weeks before or two weeks after index
  • Patients with a record of pregnancy, pregnancy termination, or hospital admissions for birth/delivery, or a positive laboratory test indicating pregnancy up to 9 months before index date
  • Known to be positive for the human immunodeficiency virus
  • Patients not receiving radiation therapy in the year after diagnosis.

Treatment and study plan

Primary outcomes

  1. Number of Truveta participants with glioblastoma

    Time frame: 01 Jan 2021 to 30 Jun 2025

    The number of Truveta participants eligible for each cohort will be determined:

    • Cohort 1: The number of adults in Truveta with newly diagnosed glioblastoma between 01 Jan 2021 and 30 Jun 2025 based on the below criteria:
    • International Classification of Diseases, Tenth Revision, clinical modification (ICD 10-CM) and/or Systematized Nomenclature of Medicine - Clinical Terms (SNOMED CT) code for malignant brain neoplasm and/or malignant glioma of brain
    • Resection/biopsy with histology submission/Isocitrate Dehydrogenase (IDH) test
    • Post-IDH test SNOMED CT code specific to glioblastoma
    • Post-resection magnetic resonance imaging (MRI)
    • Not yet treated with chemotherapy/radiation/immunotherapy by 14 days after resection.
    • Cohort 2: The number of adults in Truveta who are eligible for Cohort 1 who also meet the eligibility criteria of the Phase 2 BPM31510 trial (for which they might serve as comparison group).

  2. Completeness and quality of baseline and follow-up data in Truveta

    Time frame: 01 Jan 2021 to 30 Jun 2025

    This study will characterize baseline variables on the index date for Cohorts 1 and 2 separately in terms of:

    • Distribution of each value
    • Missing values
    • Values with incorrect units
    • Values outside a medically plausible range The index date is defined as the date on which a participant meets all eligibility criteria between 15 and 50 days after resection between 01 Jan 2021 to 30 Jun 2025. For participants who have more than one healthcare visit in which they meet all eligibility criteria, one eligible date will be randomly selected as the index date.

  3. Quality of baseline data assessment across subgroups

    Time frame: At the index visit date with a lookback period of 12 months. All participants must have at least 12 months of EHR data before the index date.

    If a meaningful amount of baseline data is missing, incorrect or medically implausible ( more than 10%), a test for bias comparing those with and without missing data across the below subgroups will be performed for Cohort 1 and Cohort 2 separately:

    • Age
    • Sex
    • US region
    • Insurance type
    • Index year

Secondary outcomes

  1. Healthcare resource utilization at baseline

    Time frame: 12 months before index.

    Healthcare resource utilization will be characterized for Cohort 1 and Cohort 2 separately in the 12 months before index based on the following:

    • Outpatient visits
    • Top 20 outpatient diagnoses
    • Hospital admissions
    • Top 20 admission diagnoses
    • Top 20 drugs used

Other outcomes

  1. Duration of follow-up

    Time frame: Up to 14 months after index (52 weeks plus an 8-week time window)

    The duration of follow up will be examined for Cohort 1 and Cohort 2 separately, including:

    • Index date to disenrollment
    • Index date to death
    • Index date to composite endpoint (death and/or disenrollment).

  2. Assessment of availability and optimal time window for contrast-enhanced brain MRIs at 26 weeks follow-up

    Time frame: Up to 7 months after index (26 weeks plus a 4-week time window)

    For a future comparison of external controls from Truveta to trial participants, a key outcome will be disease progression assessed by contrast-enhanced brain MRIs at 6 months after index.

    To determine the availability of contrast-enhanced brain MRIs and the best time window in Truveta around the 6-month analysis time point, the percent of surviving participants with a contrast-enhanced brain MRI will be assessed for Cohort 1 and Cohort 2 separately at:

    • 26 weeks ± 1 week
    • 26 weeks ± 2 weeks
    • 26 weeks ± 4 weeks

  3. Assessment of availability and optimal time window of contrast-enhanced brain MRIs at 52 weeks follow-up

    Time frame: Up to 14 months after index (52 weeks plus an 8-week time window)

    For a future comparison of external controls from Truveta to trial participants, a key outcome will be disease progression assessed by contrast-enhanced brain MRIs at 12 months after index.

    To determine the availability of contrast-enhanced brain MRIs and the best time window in Truveta around the 12-month analysis time point, the percent of surviving participants with a contrast-enhanced brain MRI will be assessed for Cohort 1 and Cohort 2 separately at:

    • 52 weeks ± 2 weeks
    • 52 weeks ± 4 weeks
    • 52 weeks ± 8 weeks

  4. Assessment of differences between patients with and without contrast-enhanced brain MRIs at 26 weeks follow-up to understand the potential for bias

    Time frame: Up to 7 months after index (26 weeks plus a 4-week time window)

    For a future comparison of external controls from Truveta to trial participants, a key outcome will be disease progression assessed by contrast-enhanced brain MRIs at 6-months after index.

    We will assess differences between patients with or without an MRI at 26 weeks to understand the potential for bias by:

    • Age
    • Sex
    • US Region
    • Insurance type
    • Index year

  5. Assessment of differences between patients with and without contrast-enhanced brain MRIs at 52 weeks follow-up to understand the potential for bias

    Time frame: Up to 14 months after index (52 weeks plus an 8-week time window)

    For a future comparison of external controls from Truveta to trial participants, a key outcome will be disease progression assessed by contrast-enhanced brain MRIs at 12-months after index.

    We will assess differences between patients with or without an MRI at 52 weeks to understand the potential for bias by:

    • Age
    • Sex
    • US Region
    • Insurance type
    • Index year

  6. Assessment of the impact of calendar time on Cohort 2 characteristics

    Time frame: Up to 14 months after index (52 weeks plus an 8-week time window)

    Baseline and follow-up characteristics of Cohort 2 will be compared by index calendar year and examined for changes in missing, incorrect or medically implausible data during follow-up, as well as for clinically relevant changes in values or variable distributions (this is descriptive, no statistical testing will be conducted).

  7. Imaging data completeness during follow-up for Cohort 2 in Truveta at 26 weeks follow-up

    Time frame: Up to 7 months after index (26 weeks plus a 4-week time window)

    The frequency of imaging (total number, time between measures, time from first to last measure, time from index to 1st, 2nd, …, last measure) in the 6-month period will be assessed for Cohort 2.

    For each measure overall means, standard deviation (SD) and range and percent of measures with incorrect or medically implausible units will be calculated.

    Imaging includes:

    • MRIs
    • Contrast-enhanced MRIs
    • CT scans

  8. Imaging data completeness during follow-up for Cohort 2 in Truveta at 52 weeks follow-up

    Time frame: Up to 14 months after index (52 weeks plus an 8-week time window)

    The frequency of imaging (total number, time between measures, time from first to last measure, time from index to 1st, 2nd, …, last measure) in the 12-month period will be assessed for Cohort 2.

    For each measure overall means, standard deviation (SD) and range and percent of measures with incorrect or medically implausible units will be calculated.

    Imaging includes:

    • MRIs
    • Contrast-enhanced MRIs
    • CT scans

  9. Drug treatment data completeness for Cohort 2 in Truveta at 26 weeks follow-up

    Time frame: Up to 7 months after index (26 weeks plus a 4-week time window)

    The frequency of drug treatment (number of patients per drug of interest, days from index to initiation, total duration, initial dose, number of cycles) in the 6-month period will be assessed for Cohort 2. For each measure overall means, standard deviation (SD) and range and percent of measures with incorrect or medically implausible units will be calculated.

    Drug treatments include:

    • Concurrent temozolomide
    • Adjuvant temozolomide
    • Second-line chemotherapy
    • Bevacizumab 1st-line treatment
    • Bevacizumab 2nd-line treatment

  10. Drug treatment data completeness for Cohort 2 in Truveta at 52 weeks follow-up

    Time frame: Up to 14 months after index (52 weeks plus an 8-week time window)

    The frequency of drug treatment (number of patients per drug of interest, days from index to initiation, total duration, initial dose, number of cycles) in the 12-month period will be assessed for Cohort 2. For each measure overall means, standard deviation (SD) and range and percent of measures with incorrect or medically implausible units will be calculated.

    Drug treatments include:

    • Concurrent temozolomide
    • Adjuvant temozolomide
    • Second-line chemotherapy
    • Bevacizumab 1st-line treatment
    • Bevacizumab 2nd-line treatment

  11. Radiotherapy data completeness for Cohort 2 in Truveta at 26 weeks follow-up

    Time frame: Up to 7 months after index (26 weeks plus a 4-week time window)

    The frequency of external beam radiation treatment in the 6-month period will be assessed for Cohort 2 through the following:

    • Total number on EBRT overall and with intensity-modulated radiation therapy, volumetric modulated arc therapy, 3D-conformal therapy and proton radiotherapy specifically
    • Time from resection to EBRT initiation
    • Number of patients initiating EBRT >56 days after resection
    • Time from index to EBRT initiation
    • Total duration of EBRT treatment
    • Initial EBRT dose
    • Number of EBRT doses received
    • Number of EBRT fractions received For each measure overall means, standard deviation (SD) and range and percent of measures with incorrect or medically implausible units will be calculated.

  12. Radiotherapy data completeness for Cohort 2 in Truveta at 52 weeks follow-up

    Time frame: Up to 14 months after index (52 weeks plus an 8-week time window)

    The frequency of external beam radiation treatment in the 12-month period will be assessed for Cohort 2 through the following:

    • Total number on EBRT overall and with intensity-modulated radiation therapy, volumetric modulated arc therapy, 3D-conformal therapy and proton radiotherapy specifically
    • Time from resection to EBRT initiation
    • Number of patients initiating EBRT >56 days after resection
    • Time from index to EBRT initiation
    • Total duration of EBRT treatment
    • Initial EBRT dose
    • Number of EBRT doses received
    • Number of EBRT fractions received For each measure overall means, standard deviation (SD) and range and percent of measures with incorrect or medically implausible units will be calculated.

  13. Subsequent resection completeness for Cohort 2 in Truveta at 26 weeks follow-up

    Time frame: Up to 7 months after index (26 weeks plus a 4-week time window)

    The frequency of subsequent resection (total number with subsequent resection, time from first to second brain surgery) in the 6-month period will be assessed for Cohort 2.

    For each measure overall means, standard deviation (SD) and range and percent of measures with incorrect or medically implausible units will be calculated.

  14. Subsequent resection completeness for Cohort 2 in Truveta at 52 weeks follow-up

    Time frame: Up to 14 months after index (52 weeks plus an 8-week time window)

    The frequency of resection (total number with subsequent resection, time from first to second brain surgery) in the 12-month period will be assessed for Cohort 2.

    For each measure overall means, standard deviation (SD) and range and percent of measures with incorrect or medically implausible units will be calculated.

  15. Post-index outpatient visit data completeness for Cohort 2 in Truveta at 26 weeks follow-up

    Time frame: Up to 7 months after index (26 weeks plus a 4-week time window)

    The frequency of post-index outpatient visits (total number, time between visits, time from first to last outpatient visit, top 20 outpatient diagnoses, top 20 outpatient procedures) in the 6-month period will be assessed for Cohort 2. For each measure overall means, standard deviation (SD) and range and percent of measures with incorrect or medically implausible units will be calculated.

  16. Post-index outpatient visit data completeness for Cohort 2 in Truveta at 52 weeks follow-up

    Time frame: Up to 14 months after index (52 weeks plus an 8-week time window)

    The frequency of post-index outpatient visits (total number, time between visits, time from first to last outpatient visit, top 20 outpatient diagnoses, top 20 outpatient procedures) in the 12-month period will be assessed for Cohort 2. For each measure overall means, standard deviation (SD) and range and percent of measures with incorrect or medically implausible units will be calculated.

  17. Post-index hospital admission data completeness for Cohort 2 in Truveta at 26 weeks follow-up

    Time frame: Up to 7 months after index (26 weeks plus a 4-week time window)

    The frequency of post-index hospital admissions (total number, time between admissions, time from first to last admission, top 20 admission diagnoses) in the 6-month period will be assessed for Cohort 2. For each measure overall means, standard deviation (SD) and range and percent of measures with incorrect or medically implausible units will be calculated.

  18. Post-index hospital admission data completeness for Cohort 2 in Truveta at 52 weeks follow-up

    Time frame: Up to 14 months after index (52 weeks plus an 8-week time window)

    The frequency of post-index hospital admissions (total number, time between admissions, time from first to last admission, top 20 admission diagnoses) in the 12-month period will be assessed for Cohort 2. For each measure overall means, standard deviation (SD) and range and percent of measures with incorrect or medically implausible units will be calculated.

Sponsors and collaborators

Lead sponsor

BPGbio

Industry

Collaborators

  • Slipstream Life Sciences
  • Truveta

Registry information

Official study title

A Retrospective Observational Cohort Study to Assess the Degree to Which the Truveta Dataset Meets FDA Fit-for-Purpose Requirements for Label-Enabling Regulatory Use for BPM31510 in Patients With Newly Diagnosed Glioblastoma

Important dates

Study start
2021
Primary completion
2026
Study completion
2026
First posted
Jun 29, 2026
Registry last updated
Jul 1, 2026

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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