Pembrolizumab and Stereotactic Radiosurgery for Melanoma or Non-Small Cell Lung Cancer Brain Metastases

Completed · Phase 1

Conditions studied: Metastatic Malignant Neoplasm in the Brain, Metastatic Melanoma, Mucosal Melanoma, Ocular Melanoma, Stage IV Non-Small Cell Lung Cancer, Stage IV Skin Melanoma, Melanoma of Unknown Primary

In brief

This pilot trial studies the side effects of giving pembrolizumab together with stereotactic radiosurgery to treat patients with melanoma or non-small cell lung cancer that has spread to the brain. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Stereotactic radiosurgery is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor and may cause less damage to normal tissue. Giving pembrolizumab together with stereotactic radiosurgery may be a better treatment for patients with melanoma or non-small cell lung cancer that has spread to the brain.

Key facts

Study ID: NCT02858869
Run by: Emory University
People needed: 25
Starts: 2016-10-04
Expected to finish: 2023-10-28
Last updated by the study team: 2026-03-09

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Be willing and able to provide written informed consent/assent for the trial
Eastern Cooperative Oncology Group (ECOG) performance scale (PS) of 0-1; Karnofsky performance status ≥ 70%
Patients must have histological diagnosis of melanoma or non-small cell lung cancer (biopsy will be done per standard of care, if needed to prove metastatic melanoma and/or NSCLC as well as for clinically relevant mutation analysis); additional biopsy will be per standard of care
Patients can be treated either in first line or in the refractory setting; programmed death-ligand 1 (PD-L1) positivity is not required for enrollment
All melanoma patients may be tested for proto-oncogene B-Raf (BRAF) as part of routine standard of care, but is not a requirement for the trial; all NSCLC patients may be tested for with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) as part of standard of care, but is not a requirement of the trial
Having gotten prior programmed cell death protein 1 (PD1) therapy is allowed for, especially if they have previously progressed on it; progression may include extra-cranial as well as intra-cranial progression; after progressing on PD1 therapy, intervening chemotherapy and/or targeted therapy (BRAF inhibitors [BRAFi], etc) is allowed; if they are on intervening chemotherapy and/or targeted therapy (BRAFi, etc), they have to have progression intra-cranially and/or extra-cranially and must be off intervening therapy for at least 2 weeks
Patient must be asymptomatic at time of getting SRS (day 0) on trial; prednisone < 10 mg/day for at least 7 days prior to treatment is allowed
Patients with ocular, mucosal and unknown primary melanoma will also be eligible
Patients with 1-10 untreated brain metastases at time of initial brain metastases diagnosis (surgery to one of the brain lesions and/or biopsy of a lesion for diagnostic purposes and/or for standard of care purposes is acceptable)
Largest brain metastases volume measures less than 14.15 cc³
Prior radiation to the primary and/or regional radiotherapy for melanoma and/or NSCLC is acceptable
Baseline labs as within standard of care (complete blood count [CBC], basic metabolic panel [BMP], lactate dehydrogenase [LDH], erythrocyte sedimentation rate [ESR], etc) are required within 14 days of enrollment
Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Patients must have at least 14 days to recover from all prior treatment, including surgery, chemotherapy, immunotherapies, prior to enrollment on this protocol
Demonstrate adequate organ function, all screening labs should be performed within 14 days of treatment initiation
Absolute neutrophil count (ANC) ≥ 1,500/mcL
Platelets ≥ 100,000/microliters (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 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
Female subject of childbearing potential should have a negative urine or serum pregnancy within 2 weeks 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

You may not qualify if…

Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
If they have brain metastases located in the brain stem (including midbrain, pons, or medulla)
Inability to undergo magnetic resonance imaging (MRI) evaluation for treatment planning and follow-up
Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
Has a known history of active TB (bacillus tuberculosis)
Hypersensitivity to pembrolizumab or any of its recipients
Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or 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: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
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 (non-infectious) pneumonitis that required steroids or current 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 specific 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

Where it is running

Emory University/Winship Cancer Institute — Atlanta, Georgia, United States

Full record on ClinicalTrials.gov

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