Cabozantinib S-malate in Treating Patients With Metastatic Pheochromocytomas or Paragangliomas That Cannot Be Removed by Surgery

Inclusion Criteria

• Histological confirmation of pheochromocytoma (PH)/paraganglioma (PG)
• Locally advanced or metastatic disease not amenable to surgery
• Patients enrolled in the main branch should have measurable disease; patients with a predominance of bone disease who have small, non-measurable or small measurable lesions other than bone, may be included per the principal investigator's discretion, in the exploratory branch of the study for patients with bone metastases only
• Progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the investigator within the 12 months preceding study enrollment
• Assessment of all known disease sites, e.g., by CT scan, MRI, bone scan as appropriate, and/or FDG-PET scan within 28 days before the first dose of cabozantinib
• Eastern Cooperative Oncology Group (ECOG) performance status = = 1500/mm^3 without colony stimulating factor support (within 4 days prior to the first dose of cabozantinib)
• Platelets >= 100, 000/mm^3 (within 4 days prior to the first dose of cabozantinib)
• Hemoglobin >= 9 g/dL (within 4 days prior to the first dose of cabozantinib)
• Bilirubin = = 2.8 g/dl (within 4 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) (within 4 days prior to the first dose of cabozantinib)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = = lower limit of normal (LLN) (within 4 days prior to the first dose of cabozantinib)
• Serum magnesium >= 1.2 mg/dL (within 4 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 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, antiestrogens, ovarian suppression or any other reversible reason

Exclusion Criteria

• Received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 3 weeks, or nitrosoureas/mitomycin C within 6 weeks before the first dose of study treatment
• Prior treatment with cabozantinib
• Radiation therapy for bone metastasis within 2 weeks, or any other external radiation therapy within 4 weeks before the first dose of study treatment; subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
• Received radionuclide treatment (i.e. iodine [I]-131 meta-iodo-benzyl guanidine) within 6 months of the first dose of study treatment
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before the first dose of study treatment
• Receipt of any other type of investigational agent within 28 days before the first dose of study treatment
• The subject has not recovered to baseline or CTCAE = = 1.3 x the laboratory ULN within 7 days before the first dose of study treatment
• The subject requires concomitant treatment,