MRI and PET to Assess Pembrolizumab Response
MRI and PET to Assess Pembrolizumab Response
The purpose of this study is to test two imaging techniques, one called whole body (WB)
 diffusion weighted (DWI) magnetic resonance imaging (MRI) (WB-DWI MRI), and another called
 Fluorine-18 3'-deoxy-3'-fluorothymidine positron emission tomography (PET) (F-18-FLT PET).
 The goal is to see whether these imaging techniques would allow the study doctors to see
 changes in the size of a tumor earlier for patients with metastatic melanoma receiving
 Pembrolizumab (MK-3475).
There is a growing body of evidence that demonstrates that tumor proliferation, measured
 classically by immunohistochemical evidence of increased Ki-67 expression, can be reliably
 determined in vivo using radiolabeled thymidine. The development of [18F]-fluorothymidine
 (FLT) PET has been reliably identified as a marker of cellular proliferation, and has been
 shown to identify changes in proliferation in successfully treated patients.
Inclusion Criteria:

 -  Histologically confirmed diagnosis of melanoma

 -  Stage III or stage IV metastatic melanoma

 -  Disease that is measurable. This is defined as lesions measuring at least 10mm on
 radiologic imaging. For lymph node disease, the lesion must measure at least 15 mm or
 have been biopsied and shown to contain melanoma. Skin or mucosal lesions that are not
 measurable on radiologic imaging but measure at least 10mm on clinical exam are also
 acceptable. (See Section 13.2 for detailed definition of measurable disease)

 -  Disease is termed unresectable or the patient refuses resection

 -  The Eastern Cooperative Oncology Group (ECOG) performance status of 1 or better

 -  Age ≥18 years. This is due to the limited data with pembrolizumab in children younger
 than 18 years of age.

 -  Normal organ and marrow function as defined below

 -  Aspartate aminotransferase (AST) (SGOT) or alanine aminotransferase (ALT) (SGPT)
 ≤2.5 × institutional upper limit of normal (≤5 x upper limit of normal for
 patient with liver metastasis)

 -  Total bilirubin within 1.5 x institutional level of normal or direct bilirubin ≤
 upper limit of normal (ULN) for patient with total bilirubin levels > 1.5 ULN)

 -  Hemoglobin ≥ 9.0g/dL or ≥5.6mmol/L

 -  Absolute neutrophil count ≥1,000/microliters (mcL)

 -  Platelets ≥ 75,000/mcL

 -  The effects of pembrolizumab on the developing human fetus are unknown. For this
 reason, women of child-bearing potential and men must agree to use adequate
 contraception (hormonal or barrier method of birth control; abstinence) prior to study
 entry and for the duration of study participation. Should a woman become pregnant or
 suspect she is pregnant while she or her partner is participating in this study, she
 should inform her treating physician immediately. Men treated or enrolled on this
 protocol must also agree to use adequate contraception prior to the study, for the
 duration of study participation, and 4 months after completion of pembrolizumab
 administration.

 -  Women of child-bearing potential must have a negative urinary or serum pregnancy test.

 Exclusion Criteria:

 -  Prior therapy with anti-PD-1 antibody

 -  The patient has symptomatic brain metastases. Asymptomatic brain metastases are
 permitted provided that there is no steroid requirement, no more than 4 metastases
 detected on standard MRI imaging, no metastatic brain lesion that is > 3 cm in size,
 and no lepto-meningeal disease.

 -  Patient has not recovered to Grade 0-1 from adverse events due to prior chemotherapy,
 radiation, or biological cancer therapy (including monoclonal antibody (mAb)).

 -  The patient is not recovered from minor or major surgery and is less than 4 weeks from
 major surgery prior to starting treatment with pembrolizumab

 -  Significant auto-immune disease requiring hospitalization within the past two years or
 any history of life-threatening auto-immune disease

 -  Immunosuppressive therapy including systemic corticosteroids except for maintenance
 dosing for adrenal insufficiency

 -  Concurrent use of any other investigational agents

 -  Active central nervous system metastasis and/or carcinomatous meningitis causing
 symptoms.

 -  Known additional malignancy that is progressing or requires active treatment with the
 exceptions of basal cell carcinoma of the skin, squamous cell carcinoma of the skin,
 or in situ cervical cancer that has undergone potentially curative therapy.

 -  Active autoimmune disease or a syndrome that requires systemic steroids or
 immunosuppressive agents with the exceptions of replacement dose steroids for adrenal
 insufficiency, vitiligo, resolved childhood asthma/atopy, intermittent use of inhaled
 steroids, local steroid injections, hypothyroidism stable on hormone replacement, and
 Sjogren's syndrome

 -  Active tuberculosis

 -  Hypersensitivity to pembrolizumab or any of its excipients.

 -  Expected to require any other form of systemic antineoplastic therapy while receiving
 pembrolizumab

 -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
 infection, autoimmune diseases, symptomatic congestive heart failure, unstable angina
 pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
 limit compliance with study requirements

 -  Patients with a pacemaker, stainless steel aneurysm clip or any other magnetic
 resonance (MR) contraindicated implant or foreign body would warrant exclusion from
 this study. Pacemakers may be reprogrammed or turned off by the strong MRI magnetic
 field. Radio-frequency (RF) fields in MR can also cause severe heating of pacemaker
 lead tips. Steel aneurysm clips are prone to torque in the strong MR field which can
 displace the clips and may damage the vessel, resulting in hemorrhage, and/or death.

 -  All patients and volunteers are screened before MR examination using a MRI safety
 screening Questionnaire as part of the New York Presbyterian/Columbia University
 Medical Center (NYP/CUMC) MRI safety policy. Any patient who would normally be
 excluded by this screening process would also be excluded from this study.

 -  Pregnant or breastfeeding women are excluded from this study because of the unknown
 effects of the study agent on the unborn child and the possible adverse impact of
 immune activation on pregnancy. Because there is an unknown but potential risk for
 adverse events in nursing infants secondary to treatment of the mother with
 pembrolizumab breastfeeding should be discontinued if the mother is treated with
 pembrolizumab.

 -  Male who is expecting to father a child during the treatment period.

 -  History of pneumonitis requiring hospitalization or systemic immune suppressive
 therapy.

 -  Significant immunodeficiency making the patient unlikely to benefit from pembrolizumab
 therapy including a diagnosis of acquired immune deficiency syndrome (AIDS), active
 hepatitis B or hepatitis C, or organ transplant requiring immunosuppressive therapy.

 -  Received a live virus vaccine within 30 days of planned start of therapy