FPS-ZM1 With or Without Dexamethasone for Controlling Post Operative Cerebral Edema in Patients With Glioblastoma

NCT07791264 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 4 other identifiers: 25116NCI-2026-05499P30CA033572U19CA264512
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, best dose and how well FPS-ZM1 works for controlling post operative cerebral edema in patients with glioblastoma. FPS-ZM1 works by blocking the pathway that controls inflammation. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving FPS-ZM1 with or without dexamethasone may be safe and/or effective in controlling post operative cerebral edema in patients with glioblastoma.

Conditions

Glioblastoma; Malignant Glioma; Recurrent Glioblastoma; Recurrent Malignant Glioma

Outcome Measures

Primary Outcomes (2)

• RAGE Antagonist FPS-ZM1 (FPS-ZM1) related adverse events

  Assessed per Common Terminology Criteria for Adverse Events (CTCAE) version 6.0.

  Up to 30 days post surgery

• Dose limiting toxicity rate

  Assessed per CTCAE version 6.0.

  Up to 30 days post surgery

Secondary Outcomes (29)

• Doses of dexamethasone taken post-operatively by study participants on dose Level 4

  Up to 30 days post surgery

• FPS-ZM1 concentrations in enhancing tumor tissue

  Up to 30 days post surgery

• FPS-ZM1 concentrations in non-enhancing tumor tissue

  Up to 30 days post surgery

• FPS-ZM1 concentrations in cerebrospinal fluid (CSF)

  Up to 30 days post surgery

• FPS-ZM1 concentrations in resection cavity fluid

  Up to 30 days post surgery

Study Arms (2)

Arm I (FPS-ZM1 and dexamethasone)

EXPERIMENTAL

Starting 2 days prior to surgery, patients receive FPS-ZM1 PO QD until post operative day 11, and dexamethasone IV or PO QD taper until post operative day 14, in the absence of disease progression or unacceptable toxicity. On day of surgery patients undergo standard of care resection and, if possible, undergo placement of a temporary peritumoral microdialysis catheter and intracavity drain for collection of dialysate and intracavity fluid. Patients undergo urine sample collection during screening, lumbar puncture with cerebrospinal fluid collection and CT scan on study and brain MRI, and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Dexamethasone; Procedure: Invasive Procedure; Procedure: Magnetic Resonance Imaging; Drug: RAGE Antagonist FPS-ZM1; Procedure: Resection

Arm II (FPS-ZM1)

EXPERIMENTAL

Starting 2 days prior to surgery, patients receive FPS-ZM1 PO QD and, if needed for physiologic replacement, a smaller dose of dexamethasone IV or PO QD until post operative day 11, in the absence of disease progression or unacceptable toxicity. On day of surgery patients undergo standard of care resection and, if possible, undergo placement of a temporary peritumoral microdialysis catheter and intracavity drain for collection of dialysate and intracavity fluid. Patients undergo urine sample collection during screening, lumbar puncture with cerebrospinal fluid collection and CT scan on study and brain MRI, and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Dexamethasone; Procedure: Invasive Procedure; Procedure: Magnetic Resonance Imaging; Drug: RAGE Antagonist FPS-ZM1; Procedure: Resection

Interventions

Biospecimen Collection PROCEDURE

Undergo blood, dialysate, intracavity fluid, and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm I (FPS-ZM1 and dexamethasone); Arm II (FPS-ZM1)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm I (FPS-ZM1 and dexamethasone); Arm II (FPS-ZM1)

Dexamethasone DRUG

Given IV or PO

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, LenaDex, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Arm I (FPS-ZM1 and dexamethasone); Arm II (FPS-ZM1)

Invasive Procedure PROCEDURE

Undergo placement of a temporary peritumoral microdialysis catheter

Also known as: Invasive

Arm I (FPS-ZM1 and dexamethasone); Arm II (FPS-ZM1)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm I (FPS-ZM1 and dexamethasone); Arm II (FPS-ZM1)

RAGE Antagonist FPS-ZM1 DRUG

Given PO

Also known as: FPS ZM1, FPS-ZM1, FPSZM1, RAGE Inhibitor FPS-ZM1

Arm I (FPS-ZM1 and dexamethasone); Arm II (FPS-ZM1)

Resection PROCEDURE

Undergo resection surgery

Also known as: Surgical Resection

Arm I (FPS-ZM1 and dexamethasone); Arm II (FPS-ZM1)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent given by the participant. Non-English speaking adults are eligible for participation if they have the capacity to understand and consent to the study procedures
• Age: ≥ 18 years
• Karnofsky Performance Status (KPS) ≥ 70%
• Histologically confirmed glioblastoma or radiographic findings consistent with a high grade glioma
• Newly diagnosed or recurrent tumor
• The patient is planning to undergo a standard-of-care craniotomy for gross total resection of enhancing tumor
• The patient's pre-operative brain MRI shows the presence of mild to moderate cerebral edema, defined as a midline shift of less than 10 mm
• Dose Levels 1-3 participants: If taking more than a total of 6 mg a day of dexamethasone at the time of signing the consent form, it is anticipated by the neurosurgeon that the participant will be able to decrease their dose of dexamethasone to 6 mg daily by 4 days before the surgery (pre-operative Day -4)
• Dose Level 4 participants: If taking more than 1 mg a day of dexamethasone at the time of signing the consent form, it is anticipated by the neurosurgeon that the participant will be able to taper their dose of dexamethasone to 1 mg daily or less by pre-operative Day -4
• The patient is not planning to be in another clinical trial during the study period
• The patient has recovered from any acute toxic effects (except alopecia) to ≤ grade 1 of prior anti-cancer therapy
• No limit to prior number of therapies. The following time periods must have elapsed prior to the start of study treatment: 6 weeks from nitrosourea-containing chemotherapy, 4 weeks from non-nitrosourea-containing cytotoxic chemotherapy (except 23 days from last daily dose of temozolomide taken in a 5 of 28 day regimen, 5 half-lives from last dose of a targeted agent, and 4 weeks from the last dose of bevacizumab). There is no time period requirement for prior radiation therapy
• Absolute neutrophil count (ANC) ≥ 1,000/mm\^3
• Platelets ≥ 100,000/mm\^3
• Hemoglobin ≥ 9g/dL

You may not qualify if:

• The patient is taking a medication that is a strong or moderate inducer or inhibitor of major CYP450 isoenzymes and drug transporters, and the patient is not able to stop that medication at least 14 days prior to start of study treatment
• The patient has a risk factor for torsades de pointes, such as structural heart disease (history of myocardial infarction, congestive heart failure, left ventricular hypertrophy), electrolyte abnormalities (hypokalemia, hypomagnesemia), bradycardia or heart blocks, or a family history of Long QT syndrome
• The patient is taking a medication that prolongs the QT/QTc interval and is not able to stop that medication at least 14 days prior to start of study treatment
• The patient is unwilling to stop taking herbal medications prior to the start of study treatment
• The patient is taking a hepatic enzyme-inducing anti-seizure medication within 14 days prior to start of study treatment
• Patient is planning to participate in clinical trial or start a new therapy for their brain tumor during the study period: Day -2 to Day 14
• Patient has not recovered from toxicities of prior therapy (must be grade 1 or less) except alopecia
• Adults who lack the capacity to provide informed consent, including individuals who would require consent from a Legally Authorized Representative (LAR)
• Clinically significant uncontrolled illness
• Active infection requiring antibiotics
• Participants with human immunodeficiency virus (HIV) are excluded due to concerns about inadvertent augmentation of infectious and/or inflammatory activity
• Undergoing treatment for another cancer
• Issues with tolerating oral medication (e.g. inability to swallow, malabsorption issues, ongoing nausea or vomiting)
• Chronic or active viral infection of the CNS
• Participant is pregnant or breastfeeding

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

Specimen Handling; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Minimally Invasive Surgical Procedures; Magnetic Resonance Spectroscopy; FPS-ZM1

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Jana L Portnow

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients assigned to dose levels 1-3 are assigned to arm I, patients assigned to dose level 4 are assigned to arm II.

Study Record Dates

• First Submitted: August 6, 2026
• First Posted: August 27, 2026
• Study Start (Estimated): February 17, 2027
• Primary Completion (Estimated): August 28, 2028
• Study Completion (Estimated): August 28, 2028
• Last Updated: August 27, 2026

Record last verified: 2026-08

Locations

US (1)