Pembrolizumab in Treating Patients with Metastatic or Locally Advanced Thyroid Gland Undifferentiated (Anaplastic) Cancer

Inclusion Criteria

• Be willing and able to provide written informed consent for the trial
• Histologically or cytologically confirmed diagnosis of anaplastic thyroid cancer or undifferentiated thyroid cancer; a diagnosis of possible anaplastic thyroid cancer (ATC)/undifferentiated thyroid cancer (UTC) will be allowed if the clinical presentation is consistent with anaplastic or undifferentiated thyroid cancer
• Patients will be eligible if they meet either criteria: * Unresectable anaplastic thyroid cancer limited to the neck: Patients must have received radiation therapy or surgery to primary tumor and have subsequent evidence of ATC * Metastatic anaplastic thyroid cancer: either with entirely surgically removed cancer/metastatic only disease, or with disease in the neck not requiring radiation or surgery to the neck mass
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Patients with a bulky thyroid/neck mass and those in whom airway obstruction is suspected should undergo an evaluation via indirect or direct laryngoscopy to ensure patency of the trachea/airway prior to enrollment
• Have a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) >= 1,500 /mcL, performed within 14 days of treatment initiation
• Platelets >= 75,000 / mcL, performed within 14 days of treatment initiation
• Hemoglobin >= 8 g/dL without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment), performed within 14 days of treatment initiation
• Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]), performed within 14 days of treatment initiation * 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, performed within 14 days of treatment initiation
• 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, performed within 14 days of treatment initiation
• Albumin >= 2.5 mg/dL, performed within 14 days of treatment initiation
• 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, performed within 14 days of treatment initiation
• 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, performed within 14 days of treatment initiation
• 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

• 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
• Patients who have received radiation therapy within 7 days prior to the first dose of treatment should be excluded; treatment-related adverse events must have resolved prior to study 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 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 acute, non- hematological adverse events due to agents administered more than 4 weeks earlier unless otherwise approved by the principal investigator * Note: Subjects with =< grade 2 neuropathy, any grade dysphagia, =< grade 2 pain, =< grade 2 weight loss, any grade hyperpigmentation of skin, any grade fatigue, any grade xerostomia, and any grade dysgeusia, are an exception to this criterion and may qualify for the study; also please note that the presence of a feeding tube to aid with nutrition does not disqualify patients from 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 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 acute, non-hematological adverse events due to a previously administered agent unless otherwise approved by the principal investigator * Note: Subjects with =< grade 2 neuropathy, any grade dysphagia, =< grade 2 pain, =< grade 2 weight loss, any grade hyperpigmentation of skin, any grade fatigue, any grade xerostomia, and any grade dysgeusia, are an exception to this criterion and may qualify for the study; also please note that the presence of a feeding tube to aid with nutrition does not disqualify patients from 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 known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
• 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, 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 received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• 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