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

A Phase 1 Study of the RAGE Inhibitor FPS-ZM1 for Controlling Post-Operative Cerebral Edema in Glioblastoma Patients

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Glioblastoma; Malignant Glioma; Recurrent Glioblastoma; Recurrent Malignant Glioma
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Procedure: Computed Tomography; Drug: Dexamethasone; Procedure: Resection; Procedure: Biospecimen Collection; Procedure: Invasive Procedure; Procedure: Invasive Procedure; Drug: RAGE Antagonist FPS-ZM1

Detailed Description

PRIMARY OBJECTIVE:

I. Determine the maximum feasible dose (MFD) of RAGE antagonist FPS-ZM1 (FPS-ZM1) administered peri-operatively to participants with newly diagnosed or recurrent glioblastoma.

SECONDARY OBJECTIVES:

I. Assess the ability of FPS-ZM1 to control participants' symptoms of post-operative cerebral edema when administered as monotherapy.

II. Describe the systemic pharmacokinetics and central nervous system (CNS) penetration of FPS-ZM1 based on concentrations of FPS-ZM1 in peripheral blood, cerebrospinal fluid (CSF), brain tumor tissue and resection cavity fluid (when obtainable).

III. Characterize cytokine concentrations over time in brain interstitial fluid, peripheral blood and resection cavity fluid (when obtainable) by dose level.

IV. Assess for evidence of RAGE inhibition in tumor tissue, CSF, brain interstitial fluid, resection cavity fluid (when obtainable) and peripheral blood by dose level.

V. Qualitatively and quantitatively assess changes in volume of cerebral edema on pre-operative brain magnetic resonance imaging (MRIs) and brain MRIs performed on post-operative Days 2 and 14 across dose levels.

OUTLINE: This is a dose-escalation study of FPS-ZM1 in combination with fixed-dose dexamethasone. Patients are assigned to 1 of 2 arms.

ARM I (DOSE LEVELS 1-3): Starting 2 days prior to surgery, patients receive FPS-ZM1 orally (PO) daily (QD) until post operative day 11, and dexamethasone intravenously (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 CSF collection and computed tomography (CT) scan on study and brain MRI, and blood sample collection throughout the study.

ARM II (DOSE LEVEL 4): 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 CSF collection and CT scan on study and brain MRI, and blood sample collection throughout the study.

After completion of study treatment, patients are followed up at day 30.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
      • Principal Investigator: Jana L. Portnow
      • Contact: Jana L. Portnow; Phone Number: 626-546-8293; Email: jportnow@coh.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• Total bilirubin ≤ 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease)
• Aspartate aminotransferase (AST) ≤ 1.5 x ULN
• Alanine aminotransferase (ALT) ≤ 1.5 x ULN
• Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min
• International Normalized Ratio (INR) OR Prothrombin (PT) ≤ 1.5 x ULN
• Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN

• Corrected QT interval (QTc) ≤ 450 ms

  • Must have a Fridericia's corrected QT interval (QTcF) ≤ 450 msec calculated with Fridericia formula
• Left ventricular ejection fraction (LVEF) ≥ 50%
• People of childbearing potential who have uteri: negative urine or serum pregnancy test

• Contraception:

  • Agreement by participants of childbearing potential or participants who are partners of people with childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy.

Contraception guidance (as per the information included in the informed consent document):

• Acceptable medically effective forms of birth control are:

  • Surgical sterilization (tubal ligation or hysterectomy, or vasectomy, as applicable),
  • Double-barrier methods (i.e. condoms, diaphragm, cervical cap, or sponge used with spermicidal gel or foam),
  • Intrauterine device (IUD) (i.e. Progestin, Copper),
  • Hormonal Contraceptives (Birth control patches, implants, pills, rings, or injections)

Exclusion Criteria:

• 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
• Coagulopathy or bleeding disorder
• Inability to undergo a brain MRI
• Inability to tolerate dexamethasone
• Any other condition that would, in the investigator's judgment, contraindicate participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (FPS-ZM1 and dexamethasone); 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: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Drug: Dexamethasone; Given IV or PO; Other Names: Decadron; Hemady; 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 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; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; LenaDex; Procedure: Resection; Undergo resection surgery; Other Names: Surgical Resection; Procedure: Biospecimen Collection; Undergo blood, dialysate, intracavity fluid, and urine sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Procedure: Invasive Procedure; Undergo placement of a temporary peritumoral microdialysis catheter; Other Names: Invasive; Procedure: Invasive Procedure; Undergo intracavity drain placement; Other Names: Invasive; Drug: RAGE Antagonist FPS-ZM1; Given PO; Other Names: FPS ZM1; FPS-ZM1; FPSZM1; RAGE Inhibitor FPS-ZM1
Experimental: Arm II (FPS-ZM1); 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: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Drug: Dexamethasone; Given IV or PO; Other Names: Decadron; Hemady; 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 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; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; LenaDex; Procedure: Resection; Undergo resection surgery; Other Names: Surgical Resection; Procedure: Biospecimen Collection; Undergo blood, dialysate, intracavity fluid, and urine sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Procedure: Invasive Procedure; Undergo placement of a temporary peritumoral microdialysis catheter; Other Names: Invasive; Procedure: Invasive Procedure; Undergo intracavity drain placement; Other Names: Invasive; Drug: RAGE Antagonist FPS-ZM1; Given PO; Other Names: FPS ZM1; FPS-ZM1; FPSZM1; RAGE Inhibitor FPS-ZM1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Cytokine concentrations in brain interstitium	Up to 30 days post surgery
Cytokine concentrations in peripheral blood	Up to 30 days post surgery
Cytokine concentrations in resection cavity fluid	Up to 30 days post surgery
Concentrations of RAGE ligands in brain extracellular fluid	Up to 30 days post surgery
Concentrations of RAGE ligands in CSF	Up to 30 days post surgery
Concentrations of RAGE ligands in resection cavity fluid	Up to 30 days post surgery
Concentrations of RAGE ligands in peripheral blood	Up to 30 days post surgery
Expression of activating markers on tumor infiltrating lymphocytes	Up to 30 days post surgery
Expression of activating markers on myeloid cells	Up to 30 days post surgery
Expression of activating markers on lymphocytes in resection cavity fluid	Up to 30 days post surgery
Expression of activating markers on myeloid cells in resection cavity fluid	Up to 30 days post surgery
Expression of activating markers on lymphocytes in peripheral blood	Up to 30 days
Expression of activating markers on myeloid cells in peripheral blood	Up to 30 days post surgery
T1 enhancing tumor volume from segmented T1-weighted magnetic resonance imaging (MRI)	Up to 30 days post surgery
Mean intratumoral perfusion from dynamic contrast enhanced (DCE)-MRI	Up to 30 days post surgery
Interstitial fluid flow from DCE-MRI	Up to 30 days post surgery
T2-FLAIR enhancing edema from segmented T2-FLAIR MRI	Up to 30 days post surgery
Mean intratumoral blood volume from relative cerebral blood volume as calculated from DSC-MRI	Up to 30 days post surgery
Mean intratumoral tissue density as measured by the apparent diffusion coefficient derived from diffusion-weighted MRI	Up to 30 days post surgery
Mean intratumoral lactate and glutatione concentration as measured by multiplexed MR spectroscopy	Up to 30 days post surgery
FPS-ZM1 plasma pharmacokinetics: Maximum Observed Plasma Concentration (Cmax)	Up to 30 days post surgery
FPS-ZM1 plasma pharmacokinetics: Area Under the Plasma Concentration-Time Curve (AUC)	Up to 30 days post surgery
FPS-ZM1 plasma pharmacokinetics: Terminal Elimination Half-Life (t½)	Up to 30 days post surgery
FPS-ZM1 plasma pharmacokinetics: Clearance (CL)	Up to 30 days post surgery

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jana L Portnow, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): February 17, 2027
• Primary Completion (Estimated): August 28, 2028
• Study Completion (Estimated): August 28, 2028

Study Registration Dates

• First Submitted: August 6, 2026
• First Submitted That Met QC Criteria: August 25, 2026
• First Posted (Actual): August 27, 2026

Study Record Updates

• Last Update Posted (Actual): August 27, 2026
• Last Update Submitted That Met QC Criteria: August 25, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma; Sulfur Compounds; Organic Chemicals; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzene Derivatives; Chemistry Techniques, Analytical; Sulfonic Acids; Sulfur Acids; Spectrum Analysis; Pregnadienetriols; Benzenesulfonates; Arylsulfonates; Arylsulfonic Acids; Dexamethasone; Calcium Dobesilate; Specimen Handling; Magnetic Resonance Spectroscopy; Minimally Invasive Surgical Procedures; dexamethasone 21-phosphate; auricularum; dexamethasone acetate; FPS-ZM1
• Other Study ID Numbers: 25116 (Other Identifier: City of Hope Medical Center); P30CA033572 (U.S. NIH Grant/Contract); U19CA264512 (U.S. NIH Grant/Contract); NCI-2026-05499 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No