Cabozantinib (XL-184) Monotherapy for Advanced Cholangiocarcinoma

Inclusion Criteria

• Participants must have unresectable or metastatic histologically or cytologically confirmed intrahepatic cholangiocarcinoma or extrahepatic cholangiocarcinoma (i.e. hilar and distal cholangiocarcinoma).
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan. See section 10 for the evaluation of measureable disease.
• Participants must have failed at least 1 but no more than 2 lines of systemic regimens for advanced cholangiocarcinoma due to disease progression or toxicity.
• Age ≥ 18 years.
• Life expectancy of ≥ 3 months.
• ECOG performance status 1,500/mcL
• Platelets > 100,000/mcL
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 2.0 x the upper limit of normal
• AST (SGOT)/ALT (SGPT) ≤ 5 X institutional upper limit of normal
• PT/PTT ≤ 1.5 x ULN
• Creatinine ≤ 1.5 or GFR ≥ 60 mL/min/1.73m2
• Lipase 140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment
• Any history of congenital long QT syndrome
• Any of the following within 6 months before the first dose of study treatment:
• unstable angina pectoris
• clinically-significant cardiac arrhythmias
• stroke (including TIA, or other ischemic event)
• myocardial infarction
• thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter (e.g. vena cava filter) are not eligible for this study)
• Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:
• Any of the following within 28 days before the first dose of study treatment
• intra-abdominal tumor/metastases invading GI mucosa
• active peptic ulcer disease,
• inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis, or appendicitis
• malabsorption syndrome
• Any of the following within 6 months before the first dose of study treatment:
• abdominal fistula
• gastrointestinal perforation
• bowel obstruction or gastric outlet obstruction
• intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more that 6 months before the first dose of study treatment.
• Other disorders associated with a high risk of fistula formation including PEG tube placement within 3 months before the first dose of study therapy
• Other clinically significant disorders such as:
• active infection requiring systemic treatment within 28 days before the first dose of study treatment
• serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment
• history of organ transplant
• concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment
• history of major surgery as follows:
• Major surgery within 3 months of the first dose of cabozantinib if there were no wound healing complications or within 6 months of the first dose of cabozantinib if there were wound complications
• Minor surgery within 1 months of the first dose of cabozantinib if there were no wound healing complications or within 3 months of the first dose of cabozantinib if there were wound complications
• Clinically significant gastrointestinal bleeding within six months of the first dose of study treatment
• Previous history of pulmonary embolism or deep venous thrombosis
• Severely impaired lung function or history of interstitial lung disease
• Concurrent malignancy (other than adequately treated non-melanoma skin cancer, superficial transitional cell carcinoma of the bladder, and cervical carcinoma in situ) diagnosed within the past 3 years or any currently active malignancy
• Psychiatric illness/social situations that would lim