Pembrolizumab and Magnetic Resonance Imaging With Ferumoxytol in Treating Patients With Non-small Cell Lung Cancer and Brain Metastases
Condition: Lung Carcinoma Metastatic in the Brain; Stage IV Lung Non-Small Cell Cancer AJCC v7
MeSH terms: Brain Neoplasms
Intervention: Ferumoxytol; Laboratory Biomarker Analysis; Magnetic Resonance Imaging; Pembrolizumab
Intervention description: Given IV; Correlative studies; Undergo MRI; Given IV
Intervention MeSH terms: Pembrolizumab; Ferrosoferric Oxide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

          -  International normalized ratio (INR) or prothrombin rime (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

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication; if
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required

          -  Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 120 days after the last dose of study medication; subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year; male subjects should agree to use an adequate
             method of contraception starting with the first dose of study therapy through 120 days
             after the last dose of study therapy

        Exclusion Criteria:

          -  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

          -  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 a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  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; subjects with significant drug or other allergies or autoimmune diseases
             may be enrolled at the investigator's discretion

          -  Subjects who have a contraindication for 3 tesla (3T) MRI: metal in their bodies (a
             cardiac pacemaker or other incompatible device), are severely agitated, or have an
             allergy to gadolinium containing contrast material

          -  Subjects with known iron overload (genetic hemochromatosis); in subjects with a family
             history of hemochromatosis, hemochromatosis must be ruled out prior to study entry
             with normal values of the following blood tests: transferrin saturation (TS) test and
             serum ferritin (SF) test; all associated costs will be paid by the study

          -  Subject who have received ferumoxytol within 3 weeks of study entry

          -  Subjects with three or more drug allergies from separate drug classes