Cabozantinib (XL-184) Monotherapy for Advanced Cholangiocarcinoma

After the screening procedures confirm that the participants are eligible to participate in the research study: A two-stage design will be employed in this study where at least 9 of the 20 patients enrolled in the first stage need to be progression-free at 16 weeks before the second stage can proceed. If this criterion is met, an additional 24 patients will be enrolled in the second stage for a total of 44 patients in the study. Patients will be treated with cabozantinib 60 mg daily administered orally continuously for 28-day cycles. Tumor assessments will be performed every 8 weeks until documented disease progression by RECIST criteria or drug intolerance. In this research study, the participant will be given a study drug-dosing diary for each treatment cycle. Each treatment cycle lasts 28 days (4 weeks), during which time the participant will be taking the study drug, cabozantinib daily. The diary will also include special instructions for taking the study drug(s). The participant will continue to take cabozantinib for as long as it is tolerated without any unacceptable side effects and the cancer does not get worse. The following tests and procedures will be done during the research study: Cycle 1 - On days 1, 8 and 15 * Medical History * Physical Exam including vital signs and height and weight * Performance Status * Review of side effects (day 8 and 15 only) * Routine blood tests (day 8 and 15 only) * TSH blood sample on day 1 only Additional research procedures during Cycle 1: \- Biomarker blood sample (about 2 teaspoons of blood) on day 3 and day 14 Cycles 2-3 - On days 1 and 15 * Medical History * Physical Exam including vital signs, height and weight * Performance Status * Review of side effects * EKG - day 1 of each cycle ONLY * Routine blood tests * Urine test on Day 1 of each cycle ONLY * Urine pregnancy test on day 1 of each cycle for women of childbearing potential * TSH blood sample on day 1 only Cycle 4 and Beyond: Day 1 ONLY * Medical History * Physical Exam including vital signs, height and weight * Performance Status * Review of side effects * EKG * Routine blood tests * TSH blood sample on day 1 only * Urine test * Urine pregnancy test for women of childbearing potential The following tests will be done every 2 cycles during the research study: * CA 19-9 blood sample * Tumor measurements * Chest/Abdominal/Pelvic CT/MRI of your tumor Planned Follow-up: The participant will return to the clinic between 30-37 days after the last dose of cabozantinib for the following tests and procedures: * Medical History * Physical Exam including vital signs, height and weight * Performance Status * Review of side effects * Routine blood tests * CA 19-9 blood sample * TSH blood sample