Surgical Window of Opportunity Study of Orally Administered BAY 2402234 in Recurrent Glioma

NCT05061251 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: BAY 2402234
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to look at how BAY 2402234 responds in body in patients with recurrent glioma.

Conditions

Glioma; IDH Mutation

Outcome Measures

Primary Outcomes (1)

• Biological activity of BAY 2402234

  The primary endpoint is to characterize the biological activity of BAY 2402234 using liquid chromatography-mass spectrometry (LC-MS). The tissue orotate:carbamoyl aspartate ratio will serve as the primary pharmacodynamic biomarker and will be characterized via LC-MS.

  3 days up tp day of surgery

Secondary Outcomes (1)

• Adverse Event Monitoring

  28 days after the final administered dose of BAY 2402234

Study Arms (1)

BAY 2402234

EXPERIMENTAL

Patients will receive 1 dose (5mg) orally, per day of BAY 2402234 for the 2 days prior to standard-of-care craniotomy for tumor resection and 1 dose on the morning of surgery, for a total of 3 administered doses.

Drug: BAY 2402234

Interventions

BAY 2402234 DRUG

Patients will receive 3 doses of 5mg each of BAY 2402234. Drug will be given Day 1 and Day 2 prior to standard-of-care craniotomy for tumor resection and 1 dose on the morning of surgery.

BAY 2402234

Eligibility Criteria

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

You may qualify if:

• Adults ≥ 18 years of age
• Histologically and/or genomically documented recurrent or progressive astrocytoma, IDH-mutant, grade 3 or 4 (diagnosis established by the presence of an IDH1 or IDH2 mutation along with grade 3 or 4 radiographic findings)
• Interval of at least 12 weeks from completion of adjuvant radiotherapy for gliomas to dosing, or surgical confirmation of recurrent disease
• Performance status measured via Karnofsky Performance Score of ≥ 60
• Confirmed measurable disease per response assessment in neuro-oncology criteria (RANO)
• Participants should have at least one 1.5cm x 1.5cm region of enhancing and non-enhancing tumor within the surgically accessible region
• Ability of neurosurgeon to resect tumor
• Laboratory values at the Screening Visit:
• ANC count ≥1,500/mm3;
• Platelets ≥150,000/mm3;
• Hemoglobin \> 9g/dL
• Total bilirubin ≤1.5 × the upper limit of normal (ULN) (subjects with Gilbert's Syndrome are allowed if direct bilirubin is within normal limits)
• Aspartate aminotransferase (AST \[SGOT\]) ≤3× the ULN
• Alanine aminotransferase (ALT \[SGPT\]) ≤3 × the ULN
• Serum creatinine ≤1.5 mg/dL or a calculated creatinine clearance ≤60 mL/min

You may not qualify if:

• Patients under age 18 (due to fundamental difference between pediatric and adult gliomas)
• Treatment with an IDH inhibitor within 90 days of enrollment
• Treatment with temozolomide less than 23 days from study initiation, treatment with CCNU or BCNU less than 42 days from study initiation, or treatment with any cancer-directed systemic therapy less than 4 weeks or 5 half-lives from study initiation, whichever is shorter
• Any immunomodulatory drug or molecularly targeted, monoclonal antibody, within 14 days prior to initiation of study drug
• Use of any investigational agents within 28 days of baseline or 5 half-lives from study initiation, whichever is shorter
• Increasing corticosteroid requirement or a dose of \>24mg per day of dexamethasone or an equivalent dose of other corticosteroids for longer than 48 hours within 7 days prior to study initiation
• Radiotherapy within 12 weeks prior to registration unless surgical confirmation of recurrent disease
• Presence of an acute or chronic toxicity of prior chemotherapy, with the exception of alopecia or lymphopenia, that has not resolved to ≤ Grade 1, as determined by National Cancer Institute CTCAE v5.0
• Major surgery within 28 days prior to initiation of study drug
• Active or clinically unstable bacterial, viral, or fungal infection requiring systemic therapy
• Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness
• Any of the following within 6 months prior to initiation of study drug: uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary or peripheral artery bypass graft surgery, transient ischemic attack
• Pulmonary embolism within 1 month prior to initiation of study drug
• Unstable cardiac dysrhythmias or persistent prolongation of the QTc interval to \>450 msec for males or \>470 msec for females
• Any contraindication to contrast-enhanced MRI examination

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• Bayer: collaborator

MeSH Terms

Conditions

Glioma

Interventions

orludodstat

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

• Kalil g Abdullah, MD, MSc

  UT Southwestern/ Simmons CC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 20, 2021
• First Posted: September 29, 2021
• Study Start: December 1, 2021
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2023
• Last Updated: January 11, 2022

Record last verified: 2021-12