Cabozantinib in Treating Patients With Locally Advanced or Metastatic Unresectable Adrenocortical Carcinoma

Inclusion Criteria

• Histological confirmation of adrenocortical carcinoma (ACC) based on either: i). Weiss Score of >= 3 in patients who had earlier surgical resection OR ii). biopsy results compatible with ACC in the context of clinical setting highly suggestive of ACC (adrenal mass > 4 cm invading surrounding organs or associated with distant metastases).
• Locally advanced or metastatic disease not amenable to surgery with curative intent with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the investigator based on an assessment of all known disease sites by computerized tomography (CT) scan or magnetic resonance imaging (MRI) of chest/abdomen/pelvis within 28 days before the first dose of cabozantinib. In patients with intravenous (IV) contrast allergy or borderline renal function, CT without IV contrast or 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) CT may be used as clinically indicated.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Recovery to baseline or = = 1500/mm^3 without colony stimulating factor support (obtained within 28 days prior to the first dose of cabozantinib).
• Platelets >= 100, 000/mm^3 (obtained within 28 days prior to the first dose of cabozantinib).
• Hemoglobin >= 9 g/dL (obtained within 28 days prior to the first dose of cabozantinib).
• Bilirubin = = 2.8 g/dl (obtained within 28 days prior to the first dose of cabozantinib).
• Serum creatinine = = 50 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used (obtained within 28 days prior to the first dose of cabozantinib).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = = 2.5 mg/dl (obtained within 28 days prior to the first dose of cabozantinib).
• Calcium >= 8 mg/dL (obtained within 28 days prior to the first dose of cabozantinib).
• Magnesium >= 1.2 mg/dL (obtained within 28 days prior to the first dose of cabozantinib).
• Potassium >= 3.0 meq/L (obtained within 28 days prior to the first dose of cabozantinib).
• Capable of understanding and complying with the protocol requirements and has signed the informed consent document.
• Sexually active patients (men and women) must agree to use medically accepted barrier methods of contraception (e.g. male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All sexually active subjects of reproductive potential must agree to use both a barrier method and a second method of birth control during the course of the study and for 4 months after the last dose of study drug(s).
• Women of childbearing potential must have a negative pregnancy test at screening. Women of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Postmenopause is defined as amenorrhea >= 12 consecutive months. Note: women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, ovarian suppression or any other reversible reason.

Exclusion Criteria

• Received cytotoxic chemotherapy, radiation therapy, or targeted therapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 28 days of study enrollment.
• For patients who received mitotane within 6 months of consenting, mitotane should have been stopped at least 28 days prior to study enrollment AND to have mitotane serum level of = 1.3 x the laboratory ULN within 28 days before the first dose of study treatment.
• Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin and Factor Xa inhibitors), platelet inhibitors (e.g., clopidogrel) or therapeutic doses of low m