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

N/AActive Not RecruitingNCT07674095

BPGbio150 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Cohort 1 inclusion Criteria: 1. 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) 2. 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 3. Patients must be adults at least 18 years of age at time of surgery 4. CPT codes indicating submission of surgical sample for pathology for IDH testing 5. SNOMED CT codes for "glioblastoma" after IDH testing 6. Note that while a diagnosis can be made based on IDH from a biopsy or resection sample, resection is required for study inclusion. 7. A post-resection CPT code for brain MRI 8. At least one visit meeting all eligibility criteria between 15- and 50-days post-resection. Cohort 1 exclusion Criteria: 1. History of malignant neoplasm of the brain \>12 months before index 2. 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: 1. Brain MRI scan post-resection available for evaluation 2. Karnofsky performance score of at least 60 3. Laboratory values within the following specified ranges: 1. Absolute neutrophil count of at least 1.5 k/microliter (μL) 2. Platelet count of at least 100 k/μL 3. Hemoglobin level of at least 9 gram/deciliter (dL) 4. Serum creatinine level of at most 1.8 milligram(mg)/dL or creatinine clearance of more than 50 milliliter/min 5. Bilirubin level of at least 1.5 mg/dL 6. ALT level of at most 3.0 × upper limit of normal (ULN) 7. AST of at most 3.0 × ULN 8. PT of at most 1.5 × ULN 9. INR of at most 1.5 × ULN 10. PTT of at most 1.5 × ULN Cohort 2 exclusion Criteria: 1. No resection was performed 2. One-year pre-index history of spontaneous or tumor-related intracranial hemorrhage 3. One-year pre-index history of diffuse leptomeningeal disease 4. Patients on dexamethasone daily dosing more than 2 mg at index 5. Three-month pre-index history of cardiovascular disease (myocardial infarction, coronary artery disease, arrhythmia, unstable angina pectoris, cerebrovascular accident) 6. Six-month pre-index history of acquired coagulopathies (hemorrhagic disorder due to circulating anticoagulants or acquired coagulation factor deficiency) 7. Six-month pre-index history of clinically significant bleeding 8. 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) 9. Six-month pre-index history of significant psychiatric illness 10. Six-month pre-index history of major infection 11. Prior malignancy except for non-melanoma skin cancer and carcinoma in situ of the cervix or bladder 12. Receiving any of the following medications at the index date: 1. Any anticoagulant, including low-molecular weight heparin and warfarin within two months pre-index 2. Any digitalis alkaloid (digoxin, digitoxin, lanatoside C) within two months pre-index 3. Antiangiogenic drugs (e.g., bevacizumab) two weeks before or two weeks after index 4. Theophylline two weeks before or two weeks after index 13. 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 14. Known to be positive for the human immunodeficiency virus 15. Patients not receiving radiation therapy in the year after diagnosis.

Outcomes

Primary Outcomes

Number of Truveta participants with glioblastoma

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).

Time frame: 01 Jan 2021 to 30 Jun 2025

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

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.

Time frame: 01 Jan 2021 to 30 Jun 2025

Quality of baseline data assessment across subgroups

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

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.

Secondary Outcomes

Healthcare resource utilization at baseline

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

Time frame: 12 months before index.