Ferumoxytol MRI in Assessing Response to Pembrolizumab in Patients With Glioblastoma

NCT03347617 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: STUDY00016046NCI-2017-02008K08CA237809
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase II trial studies how well ferumoxytol magnetic resonance imaging (MRI) works in assessing response to pembrolizumab in patients with glioblastoma. Diagnostic procedures, such as ferumoxytol MRI, may help measure a patient's response to pembrolizumab treatment.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (2)

• Specificity of Identifying Pseudoprogression

  Sensitivity and specificity are measures for the diagnostic performance of rCBV (relative cerebral blood volume) to distinguish between pseudoprogression and true progression. Sensitivity measures how well Fe-SS-rCBV identifies those who have true progression, and specificity those who have psuedoprogression. Because rCBV is a continuous variable, the cutoff point for this analysis was 1.75.

  At suspected progression, up to two years.

• Sensitivity of Identifying True Progression

  The calculation of sensitivity is based on steady state rCBV (relative cerebral blood volume) at suspected progression. Cutoff point 1.75. Sensitivity and specificity are measures for the diagnostic performance of rCBV (relative cerebral blood volume) to distinguish between pseudoprogression and true progression. Sensitivity measures how well Fe-SS-rCBV identifies those who have true progression, and specificity those who have psuedoprogression. Because rCBV is a continuous variable, the cutoff point for this analysis was 1.75.

  At suspected progression, up to two years.

Secondary Outcomes (5)

• Progression Free Survival

  Until off study, up to 5 years.

• Overall Survival

  Until off study, up to 5 years.

• Duration of Best Response

  Until off study, up to 5 years.

• Disease Response

  Until off study, up to 5 years.

• Determine the Safety and Toxicity of Pembrolizumab When Used in Combination With Standard of Care Chemo Radiation.

  30 days after last dose of pembrolizumab, up to 2 years.

Study Arms (1)

Diagnostic (Ferumoxytol MRI, pembrolizumab)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 2 years or 35 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive ferumoxytol IV and undergo MRI scans at baseline, 4 weeks after the last day of standard of care stereotactic radiosurgery or chemoradiotherapy, every 9 weeks thereafter until suspected radiographic progression, and then within 4 weeks from suspected radiographic progression.

Drug: Ferumoxytol; Other: Laboratory Biomarker Analysis; Procedure: Magnetic Resonance Imaging; Biological: Pembrolizumab

Interventions

Ferumoxytol DRUG

Given IV

Also known as: Feraheme, Ferumoxytol Non-Stoichiometric Magnetite

Diagnostic (Ferumoxytol MRI, pembrolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Diagnostic (Ferumoxytol MRI, pembrolizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo ferumoxytol MRI

Also known as: Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Diagnostic (Ferumoxytol MRI, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Diagnostic (Ferumoxytol MRI, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial
• Have a life expectancy of at least 6 months
• Have a histologically confirmed diagnosis of:
• Newly diagnosed glioblastoma (World Health Organization \[WHO\] grade IV)
• Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 on stable or reducing dose of steroids for symptom management (not more than 8 mg of dexamethasone or equivalent per day) for 5 days prior to enrollment; change in glucocorticoid dose for any purpose other than to modulate symptoms from an adverse event; Note: The use of physiologic doses (e.g., prednisone 10 mg) of corticosteroids may be approved after consultation with Merck \& Co; use of prophylactic corticosteroids to avoid allergic reactions (e.g. IV contrast dye) is permitted
• At least 14 days from any major surgeries including brain biopsy before the start of study drug pembrolizumab
• Absolute neutrophil count (ANC) \>= 1,500/mcL
• Platelets \>= 100,000/mcL
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases
• Albumin \>= 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

You may not qualify if:

• Has a diagnosis of immunodeficiency including human immunodeficiency virus (HIV) (HIV 1/2 antibodies) and is not on continuous daily immunosuppressive therapy within 7 days prior to the first dose of trial treatment; (an exception to this is the use of steroids for brain edema and resulting symptom); subjects may receive a stable or reducing dose of steroids (up to 8 mg dexamethasone or equivalent for at least 5 days prior to signing consent) to prevent or manage cerebral edema; subjects requiring over 8mg of dexamethasone per day on or five days prior to signing consent are excluded)
• Has a known history of active TB (Bacillus tuberculosis)
• Hypersensitivity to pembrolizumab or ferumoxytol or any of their excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has known history of, or any evidence of active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
• Has known active hepatitis B (e.g., hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (e.g., hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] \[qualitative\] is detected)
• Has received a live vaccine within 30 days of planned start of study therapy; Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
• Subjects with clinically significant signs of uncal herniation, such as acute pupillary enlargement, rapidly developing motor changes (over hours), or rapidly decreasing level of consciousness, are not eligible
• Subjects with known allergic or hypersensitivity reactions to parenteral iron, parenteral dextran, parenteral iron-dextran, or parenteral iron-polysaccharide preparations (Ferumoxytol Investigator's Drug Brochure, 2009); subjects with significant drug or other allergies or autoimmune diseases may be enrolled at the investigator's discretion

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

Ferrosoferric Oxide; Magnetic Resonance Spectroscopy; pembrolizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Ferrous Compounds; Minerals; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Results Point of Contact

• Title: Amy Huddleston
• Organization: Oregon Health and Science University

huddlesa@ohsu.edu

5034942910

Study Officials

• Leslie Muldoon, Ph.D.

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 2, 2017
• First Posted: November 20, 2017
• Study Start: December 20, 2017
• Primary Completion: December 31, 2023
• Study Completion: June 23, 2025
• Last Updated: September 9, 2025
• Results First Posted: September 9, 2025

Record last verified: 2025-09

Locations

US (1)