Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Nervous System Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Neoplasm Metastasis

Body Weight

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Pharmaceutical Solutions

Pembrolizumab

Ferrosoferric Oxide

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Parenteral Nutrition Solutions

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.

Ferumoxytol

Laboratory Biomarker Analysis

Magnetic Resonance Imaging

Edward Neuwelt, MD

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.

PRIMARY OBJECTIVE:

I. Determine the sensitivity and specificity of relative cerebral blood volume (rCBV) measured by steady state magnetic resonance imaging (MRI) with ferumoxytol in predicting true versus (vs) pseudoprogression after stereotactic radiosurgery (SRS) and intravenous (IV) pembrolizumab in subjects with brain metastases from non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. Evaluate the safety and tolerability of pembrolizumab when given with SRS in subjects with brain metastasis.

II. Evaluate progression free survival, overall survival, best response in brain disease, best response in systemic disease, and duration of best responses of brain and systematic diseases.

EXPLORATORY OBJECTIVES:

I. Compare the immune response as determined by the volume, pattern and intensity of delayed (24 hour \[hr\]) ferumoxytol uptake between subjects who develop true vs pseudoprogression.

II. Investigate the serum immunological parameters and correlate clinical as well as radiological response with systemic immune response to pembrolizumab as measured by immunological panel.

III. Compare the changes percentage expression in PDL-1 in the biopsy tissue before and after therapy at the time of progression.

IV. In subjects with measurable systemic lesions, investigate the feasibility of measuring vascular volume fraction (VVF), vessel size index (VSI) and vessel density index (VDI) as surrogate for response (true vs. pseudoprogression, as measured with Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria).

OUTLINE:

Patients receive pembrolizumab intravenously (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.

After completion of study treatment, patients are followed up at 30 days, every 12 weeks for up to 1 year, and then every 6 months thereafter.

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

The Use of Perfusion MRI Using Ferumoxytol and Small Molecular Weight Gadolinium (Gd) Agents to Assess Response to Pembrolizumab in Brain Metastases and Systemic Lesions in NSCLC: A Comparison of Imaging Modalities to Address Brain Metastases, Pseudoprogression, and Systemic Lesion Tumor Flare (Neuro-Check Pilot)

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.

Safety and tolerability will be determined using the Common Terminology Criteria for Adverse Events V4.0 (CTCAE) grades. They will be analyzed using percentages of patients who developed adverse events and exact 95% confidence intervals.

The duration of best response in brain and the duration of best response in systemic disease will be measured in months from the date on which criteria are met for complete response, partial response or stable disease until the first date that recurrent or progressive disease is objectively documented. Durations of best response will be analyzed using the Kaplan-Meier product limit estimates, taking censoring into account.

Best response in brain disease will be measured based on brain MRI scan showing the best response to treatment and analyzed using proportions of categories of best response (e.g., complete remission, partial remission, progression, stable disease etc.) and exact 95% confidence intervals.

Best response in systematic disease will be measured based on body CT scan showing the best response to treatment and analyzed using proportions of categories of best response (e.g., complete remission, partial remission, progression, stable disease etc.) and exact 95% confidence intervals.

Progression free survival will be measured in months from the date of diagnosis to the date of documented progression for each patient. Results will be analyzed using the Kaplan-Meier product limit estimates for all patients, taking censoring into account.

Overall survival will be measured in months from date of diagnosis to date of death. Results will be analyzed using the Kaplan-Meier product limit estimates for all patients, taking censoring into account.

Merck Sharp & Dohme LLC

Oregon Health and Science University

OHSU Knight Cancer Institute

Principal Investigator

Adverse experiences will be graded and recorded according to NCI CTCAE Version 4.0. Toxicities will be characterized in terms regarding seriousness, causality, toxicity grading, and action taken with regard to trial treatment

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.

Ferumoxytol: Given IV

Laboratory Biomarker Analysis: Correlative studies

Magnetic Resonance Imaging: Undergo MRI

Pembrolizumab: Given IV

Treatment (Pembrolizumab, Ferumoxytol MRI)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

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

Gerda Teglassy, MD

Due to low accrual and staffing issues, data was not collected for this outcome.

Spots Global Cancer Trial Database for lung carcinoma metastatic in the brain