Pembrolizumab and Magnetic Resonance Imaging With Ferumoxytol in Treating Patients With Non-small Cell Lung Cancer and Brain Metastases

NCT03325166 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: STUDY00016709NCI-2017-01730
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase II trial study evaluates the usefulness of the ferumoxytol steady state magnetic resonance imaging (MRI) technique for response assessment after pembrolizumab and radiation therapy in non-small cell lung cancer that has spread to the brain (brain metastases). The interactions of monoclonal antibodies such as pembrolizumab, and the body's immune system may result in an anti-tumor effect. However, it may also increase inflammation around the tumor which cannot be differentiated from true tumor growth on standard MRI. This study evaluates ferumoxytol as an MRI contrast agent to differentiate this treatment related inflammation from true tumor growth.

Conditions

Lung Carcinoma Metastatic in the Brain; Stage IV Lung Non-Small Cell Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Sensitivity and Specificity of Relative Cerebral Blood Volume

  Will be analyzed using proportions and exact 95% confidence intervals. Sensitivity analysis will be based on subjects (lesions) with surgical results, and specificity analysis will be based on lesions with pseudo-progression determined based on surgical results or follow-up scan.

  Up to 2 years

Secondary Outcomes (6)

• Safety and Tolerability of Pembrolizumab When Given With Stereotactic Radiosurgery (SRS) in Subjects With Brain Metastasis

  Up to 2 years

• Duration of Best Response of Brain and Systematic Disease

  Up to 2 years

• Best Response in Brain Disease

  Up to 2 years

• Best Response in Systematic Disease

  Up to 2 years

• Progression Free Survival

  Up to 2 years

Study Arms (1)

Treatment (pembrolizumab, ferumoxytol MRI)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years (or up to 32 cycles) in the absence of disease progression or unacceptable toxicity. Patients also receive ferumoxytol IV and undergo MRI at baseline, 12 weeks after radiation, at suspected radiographic progression, and 6 weeks after 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

Treatment (pembrolizumab, ferumoxytol MRI)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, ferumoxytol MRI)

Magnetic Resonance Imaging PROCEDURE

Undergo 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

Treatment (pembrolizumab, ferumoxytol MRI)

Pembrolizumab BIOLOGICAL

Given IV

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

Treatment (pembrolizumab, ferumoxytol MRI)

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 histologically confirmed diagnosis of NSCLC
• Have up to ten measurable (by Response Assessment in Neuro-Oncology Criteria \[RANO\]) brain metastasis planned for stereotactic radiosurgery
• Have PD-L1 expression of greater than 1%
• Subjects may already be receiving PD-(L)1 (including pembrolizumab or other PD-\[L\]1 inhibitors such as nivolumab, atezolizumab, avelumab, durvalumab) for the treatment of systemic disease; a washout period of at least 3 weeks is required from the last dose of PD-(L)1 inhibitor
• Subjects with EGFR or ALK genomic tumor aberrations should have documented disease progression on Food and Drug Administration (FDA)-approved therapy for these aberrations; subjects with EGFR or ALK genomic tumor aberrations who develop new brain metastases may be included at the discretion of the treating physician
• Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• 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
• Creatinine clearance should be calculated per institutional standard
• 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 glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases
• Albumin \>= 2.5 mg/dL

You may not qualify if:

• Has evidence of leptomeningeal disease on MRI or in cerebrospinal fluid (CSF)
• If tumor demonstrates EGFR or ALK genomic tumor aberrations, subject should have documented disease progression on FDA-approved therapy for these aberrations
• Has a diagnosis of immunodeficiency and is not on continuous daily immunosuppressive therapy within 7 days prior to the first dose of trial treatment; (subjects may receive steroids before or after SRS to prevent or manage cerebral edema; inhalational steroids are permitted)
• Has previously progressed on a PD-1 or PD-L1 checkpoint inhibitor for systemic disease
• Has a known history of active TB (Bacillus tuberculosis)
• Has hypersensitivity to pembrolizumab, gadolinium, 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
• Note: The use of denosumab is an exception to this criterion
• Subject who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
• Note: Subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• Note: Subjects with =\< grade 2 hematologic toxicities are an exception to this criterion and may qualify for the study
• Note: Subjects with =\< grade 2 fatigue are an exception to this criterion and may qualify for the study
• 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 (eg., 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Merck Sharp & Dohme LLC: collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Interventions

Ferrosoferric Oxide; Magnetic Resonance Spectroscopy; pembrolizumab

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

Due to very low enrollment and staffing issues, data was not collected for analysis of study outcomes.

Results Point of Contact

• Title: Gerda Teglassy, MD
• Organization: Oregon Health and Science University

tothg@ohsu.edu

503-494-4526

Study Officials

• Edward Neuwelt, MD

  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: October 6, 2017
• First Posted: October 30, 2017
• Study Start: November 3, 2017
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: August 10, 2022
• Results First Posted: August 10, 2022

Record last verified: 2022-07

Locations

US (1)