Adrenocortical Carcinoma Clinical Trials

• Be willing and able to provide written informed consent for the trial.

• Be ≥ 15 years of age on day of signing informed consent.

• Have histologically- or cytologically- confirmed metastatic ACC with symptomatic liver metastases.

• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or

• Adequate performance status:

‣ Patients \< 16 years of age: Lansky ≥ 50%

⁃ Patients ≥ 16 years of age: Karnofsky ≥ 50%

• Have measurable disease based on RECIST v1.1.

• Have radiologic documentation of extrahepatic tumor, defined as extrahepatic metastases.

• Consent for use of archived tissue for research purposes. Archival tissue (1 block or 20 unstained slides) will be requested, when available.

• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 28 days of treatment initiation.

∙ Table 1: Adequate Organ Function Laboratory Value

∙ Hematological Absolute neutrophil count (ANC) ≥1,500 / mcL Platelets ≥100,000 / mcL

∙ Renal Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN

∙ \*Creatinine clearance should be calculated per institutional standard.

∙ Hepatic Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 5 X ULN

∙ Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) ≤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 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 subjects of childbearing potential should have a negative serum pregnancy test within 72 hours prior to beginning treatment on study. 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 (Reference Section 10.6.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free of 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.

∙ Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.