No gastrointestinal disorders associated with a high risk of perforation or fistula formation within months prior to registration:\r\n* Active peptic ulcer disease\r\n* Inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n* Known malabsorption syndrome\r\n* Bowel obstruction or gastric outlet obstruction\r\n* Percutaneous endoscopic gastrostomy (PEG) tube placement The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders including:\r\n** Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening\r\n** Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > mm Hg systolic or > mm Hg diastolic despite optimal antihypertensive treatment within days of the first dose of cabozantinib\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within months before the first dose of cabozantinib: unstable angina pectoris; clinically-significant cardiac arrhythmias; stroke (including transient ischemic attack [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)\r\n* Gastrointestinal (GI) disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n** Any of the following within days before the first dose of cabozantinib: intra-abdominal tumor/metastases invading GI mucosa; patients must be completely recovered from any evidence of active peptic ulcer disease; patients must be completely recovered from these conditions - any evidence or inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis; malabsorption syndrome\r\n** Any of the following within months before the first dose of cabozantinib: 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 than months before the first dose of cabozantinib\r\n* Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within months before the first dose of study therapy\r\n* Other clinically significant disorders such as:\r\n** Active infection requiring systemic treatment within days before the first dose of cabozantinib\r\n** Serious non-healing wound/ulcer/bone fracture within days before the first dose of cabozantinib\r\n** History of organ transplant\r\n** Concurrent uncompensated hypothyroidism or thyroid dysfunction within days before the first dose of cabozantinib The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders including:\r\n** Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening\r\n** Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > mm Hg systolic or > mm Hg diastolic despite optimal antihypertensive treatment within days of the first dose of study treatment\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within months before the first dose of study treatment:\r\n*** Unstable angina pectoris\r\n*** Clinically-significant cardiac arrhythmias\r\n*** Stroke (including transient ischemic attack [TIA], or other ischemic event)\r\n*** Myocardial infarction\r\n*** Thromboembolic event requiring therapeutic anticoagulation (note: subjects with a venous filter [eg, vena cava filter] are not eligible for this study)\r\n* GI disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n** Active peptic ulcer disease, inflammatory bowel disease (eg, Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction\r\n** Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within months before randomization, Note: complete healing of an intra-abdominal abscess must be confirmed prior to randomization\r\n* Other clinically significant disorders that would preclude safe study participation The participant has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders including:\r\n** Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening\r\n** Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > mmHg systolic, or > mmHg diastolic despite optimal antihypertensive treatment within days of the first dose of study treatment\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within months before the first dose of study treatment:\r\n*** Unstable angina pectoris\r\n*** Clinically-significant cardiac arrhythmias\r\n*** Stroke (including transient ischemic attack [TIA], or other ischemic event)\r\n*** Myocardial infarction\r\n*** Thromboembolic event requiring therapeutic anticoagulation (note: participants with a venous filter [e.g. vena cava filter] are not eligible for this study)\r\n* Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n** Any of the following within days before the first dose of study treatment\r\n*** Active peptic ulcer disease\r\n*** Inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n*** Malabsorption syndrome\r\n** Any of the following within months before the first dose of study treatment:\r\n*** Abdominal fistula\r\n*** Gastrointestinal perforation\r\n*** Bowel obstruction or gastric outlet obstruction\r\n*** 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 than months before the first dose of study treatment The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders such as uncontrolled arrhythmias or uncontrolled congestive heart failure\r\n* Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n** Any of the following at the time of screening\r\n*** Active peptic ulcer disease,\r\n*** Active inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n** Any of the following within months before the first dose of study treatment:\r\n*** History of abdominal fistula\r\n*** Bowel perforation (Note: subjects with a venous filter (e.g. vena cava filter) are not eligible for this study) b. gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including: i. any of the following within days before the first dose of study treatment: intra-abdominal tumor/metastases invading GI mucosa, active peptic ulcer disease; patients must be completely recovered, inflammatory bowel disease (including ulcerative colitis and Crohns disease), acute pancreatitis, pancreatic duct or common bile duct obstruction, acute diverticulitis, acute cholecystitis, symptomatic cholangitis or recent appendicitis within month of first dose of cabozantinib; patients must be completely recovered from these conditions, clinically significant malabsorption syndrome, c. endocrine disorders, uncontrolled Cushing syndrome despite of adequate medical therapy. Any of the following within 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 than months before the first dose of study treatment. Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within days before the first dose of study therapy. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders including:\r\n** Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening;\r\n** Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > mm Hg systolic or > mm Hg diastolic despite optimal antihypertensive treatment within days of the first dose of study treatment;\r\n** Any history of congenital long QT syndrome;\r\n** Any of the following within months before the first dose of study treatment:\r\n*** Unstable angina pectoris;\r\n*** Clinically-significant cardiac arrhythmias;\r\n*** Stroke (including transient ischemic attack (TIA), or other ischemic event);\r\n*** Myocardial infarction;\r\n* GI disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n** Tumors invading the GI tract, active peptic ulcer disease, active inflammatory bowel disease (e.g., Crohns disease), active diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction\r\n** Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within months before randomization, Note: complete healing of an intra-abdominal abscess must be confirmed prior to randomization\r\n* Other clinically significant disorders that would preclude safe study participation Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, (eg, Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction, abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within months before randomization Any of the following within months of registration: active peptic ulcer disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, malabsorption syndrome; any of the following within months of registration: intra-abdominal abscess, gastrointestinal obstruction requiring parenteral hydration and/or nutrition, gastrointestinal perforation; note: complete resolution of an intra-abdominal abscess must be confirmed prior to registration even if the abscess occurred more than months prior to registration The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders including:\r\n** Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening\r\n** Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > mm Hg systolic or > mm Hg diastolic despite optimal anti-hypertensive treatment within days of the first dose of study treatment\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within months before the first dose of study treatment:\r\n*** Unstable angina pectoris\r\n*** Clinically-significant cardiac arrhythmias\r\n*** Stroke (including transient ischemic attack (TIA), or other ischemic event)\r\n*** Myocardial infarction\r\n* GI disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n** Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction\r\n** Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within months before first dose of study treatment Note: Complete healing of an intra-abdominal abscess must be confirmed prior first dose of study treatment\r\n* Other clinically significant disorders that would preclude safe study participation The subject has experienced any of the following:\r\n* Clinically-significant GI bleeding within months before the first dose of study treatment;\r\n* Gastrointestinal (GI) disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n** Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction\r\n** Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within months before randomization,\r\n** Note: complete healing of an intra-abdominal abscess must be confirmed prior to randomization\r\n* Hemoptysis of >= . teaspoon (.ml) of red blood within months before the first dose of study treatment;\r\n* Any other signs indicative of pulmonary hemorrhage within months before the first dose of study treatment\r\n* Patient who have developed or have had history of pulmonary hemorrhage while on carfilzomib will be excluded (fatal pulmonary hemorrhage has been observed with carfilzomib) Has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders:\r\n** Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias\r\n** Uncontrolled hypertension defined as sustained blood pressure (BP) > mm Hg systolic or > mm Hg diastolic despite optimal antihypertensive treatment\r\n** Stroke (including transient ischemic attack [TIA]), myocardial infarction, or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within months before randomization\r\n* Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:\r\n** Tumors invading the GI-tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction\r\n** Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within months before randomization; complete healing of an intra-abdominal abscess must be confirmed before study initiation\r\n* Has clinically significant hematuria, hematemesis, or hemoptysis of > . teaspoon within months before randomization\r\n* Known endobronchial disease manifestation; patients with suspected endobronchial disease on imaging who have no evidence of endobronchial disease on bronchoscopy are allowed; patients with treated endobronchial disease are also allowed provided they are stable\r\n* Lesions invading major pulmonary blood vessels Any of the following within days before the first dose of study treatment\r\n* Intra-abdominal tumor/metastases invading gastrointestinal (GI) mucosa\r\n* Active peptic ulcer disease\r\n* Inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n* Malabsorption syndrome The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders including:\r\n** Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening\r\n** Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > mm Hg systolic, or > mm Hg diastolic despite optimal antihypertensive treatment within days of the first dose of study treatment\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within months before the first dose of study treatment:\r\n*** Unstable angina pectoris\r\n*** Clinically-significant cardiac arrhythmias\r\n*** Stroke (including transient ischemic attack [TIA], or other ischemic event)\r\n*** Myocardial infarction\r\n*** Thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)\r\n* Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n** Any of the following within days before the first dose of study treatment\r\n*** Intra-abdominal tumor/metastases invading GI mucosa\r\n*** Active peptic ulcer disease,\r\n*** Inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n*** Malabsorption syndrome\r\n** Any of the following within months before the first dose of study treatment:\r\n*** Abdominal fistula\r\n*** Gastrointestinal perforation\r\n*** 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 than months before the first dose of study treatment The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders including:\r\n** Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening\r\n** Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > mm Hg systolic, or > mm Hg diastolic despite optimal antihypertensive treatment within days of the first dose of study treatment\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within months before the first dose of study treatment:\r\n*** Unstable angina pectoris\r\n*** Clinically-significant cardiac arrhythmias\r\n*** Stroke (including transient ischemic attack [TIA], or other ischemic event)\r\n*** Myocardial infarction\r\n*** Thromboembolic event requiring therapeutic anticoagulation (note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)\r\n* Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n** Any of the following within days before the first dose of study treatment\r\n*** Intra-abdominal tumor/metastases invading GI mucosa\r\n*** Any evidence of active peptic ulcer disease, patients must be completely recovered\r\n*** Any evidence of inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, patients must be completely recovered from these conditions\r\n*** Malabsorption syndrome\r\n** Any of the following within months before the first dose of study treatment:\r\n*** Abdominal fistula\r\n*** Gastrointestinal perforation\r\n*** Bowel obstruction or gastric outlet obstruction\r\n*** 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 than months before the first dose of study treatment\r\n* Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within months before the first dose of study therapy \r\n* Other clinically significant disorders such as:\r\n** Active infection requiring systemic treatment within days before the first dose of study treatment\r\n** Serious non-healing wound/ulcer/bone fracture within days before the first dose of study treatment\r\n** History of organ transplant\r\n** Concurrent uncompensated hypothyroidism or thyroid dysfunction within days before the first dose of study treatment\r\n** History of major surgery as follows:\r\n*** Major surgery within weeks before the first dose of study treatment; complete wound healing from major surgery must have occurred month before the first dose of study treatment\r\n*** Minor surgery (including uncomplicated tooth extractions) within days before the first dose of study treatment with complete wound healing at least days before the first dose of study treatment; subjects with clinically relevant ongoing complications from prior surgery are not eligible Active gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation; subjects with enteric stomata (such as ileostomy, colostomy) are also excluded:\r\n* Tumors invading the GI-tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction\r\n* Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intraabdominal abscess within weeks before enrollment; NOTE: complete healing of an intra-abdominal abscess must be confirmed before enrollment Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: a. cardiovascular disorders including: i. congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening, ii. concurrent uncontrolled hypertension defined as sustained blood pressure > mm Hg systolic, or > mm Hg diastolic despite optimal antihypertensive treatment within days of the first dose of study treatment, iii. any history of congenital long QT syndrome, or iv. any of the following within months before the first dose of study treatment: unstable angina pectoris, clinically-significant cardiac arrhythmias, stroke (including transient ischemic attack [TIA], or other ischemic event), myocardial infarction, or thromboembolic event requiring therapeutic anticoagulation (note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)\r\n* Gastrointestinal disorders, particularly those associated with a high risk of perforation or fistula formation, including: i. any of the following within days before the first dose of study treatment: intra-abdominal tumor/metastases invading GI mucosa, active peptic ulcer disease (patients must be completely recovered), inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis (patient must be completely recovered from these conditions), malabsorption syndrome; ii. any of the following within months before the first dose of study treatment: abdominal fistula, gastrointestinal perforation, bowel obstruction or gastric outlet obstruction, or intra-abdominal abscess (complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with cabozantinib even if the abscess occurred more than months before the first dose of study treatment); c. other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within months before the first dose of study therapy, d. other clinically significant disorders such as: i. active infection requiring systemic treatment within days before the first dose of study treatment, ii. serious non-healing wound/ulcer/bone fracture within days before the first dose of study treatment, iii. history of organ transplant, iv. concurrent uncompensated hypothyroidism or thyroid dysfunction within days before the first dose of study treatment, or v. major surgery within weeks before the first dose of study treatment; complete wound healing from major surgery must have occurred month before the first dose of study treatment; minor surgery within days before the first dose of study treatment with complete wound healing at least days before the first dose of study treatment; subjects with clinically relevant ongoing complications from prior surgery are not eligible The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders including:\r\n** Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening;\r\n** Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) > mm Hg systolic or > mm Hg diastolic despite optimal antihypertensive treatment within days of the first dose of study treatment;\r\n** Any history of congenital long QT syndrome;\r\n** Any of the following within months before the first dose of study treatment:\r\n*** Unstable angina pectoris;\r\n*** Clinically-significant cardiac arrhythmias;\r\n*** Stroke (including transient ischemic attack (TIA), or other ischemic event);\r\n*** Myocardial infarction;\r\n* GI disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n** Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction\r\n** Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within months before randomization \r\n*** Note: Complete healing of an intra-abdominal abscess must be confirmed prior to randomization. Also no pre-existing fistula of head and neck area; no pre-existing osteonecrosis of jaw (ONJ)\r\n* Other clinically significant disorders that would preclude safe study participation Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n* Any of the following within days before the first dose of study treatment\r\n** Intra-abdominal tumor/metastases invading GI mucosa\r\n** Active peptic ulcer disease,\r\n** Inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n** Malabsorption syndrome\r\n* Any of the following within months before the first dose of study treatment:\r\n** Abdominal fistula\r\n** Gastrointestinal perforation\r\n** Bowel obstruction or gastric outlet obstruction\r\n** 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 than months before the first dose of study treatment The following are additional exclusion criteria for patients enrolling in expansion cohort C:\r\n* Uncontrolled blood pressure (> /); patients should have a blood pressure of =< / taken by a medical professional within one week of starting on study\r\n* Proteinuria > + on urinalysis\r\n* Serosal involvement of the bowel that would render the patient at increased risk of gastrointestinal perforation\r\n* Other gastrointestinal orders that could increase the potential risk of perforation or fistula formation, including but not limited to the following:\r\n** Intra-abdominal metastases/tumor invading the gastrointestinal (GI) mucosa\r\n** Active peptic ulcer disease within days of registration\r\n** Inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis, or appendicitis\r\n* Any of the following within months of registration:\r\n** Abdominal fistula\r\n** Gastrointestinal perforation\r\n** Bowel obstruction or gastric outlet obstruction\r\n** Note: patients requiring drainage gastrostomy (e.g., PEG tube) and/or parenteral hydration and/or nutrition are not eligible\r\n** Intraabdominal abscess\r\n** Note: complete resolution of an intraabdominal abscess must be confirmed prior to registration even if the abscess occurred more than months prior to registration\r\n* Major surgery within months of the first dose of study drugs if there were no wound healing complications or within months of the first dose of study drugs if there were wound complications Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n* Any of the following at the time of screening\r\n** Intra-abdominal tumor/metastases invading gastrointestinal (GI) mucosa\r\n** Active peptic ulcer disease\r\n** Inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n* Any of the following within months before the first dose of study treatment; history of 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 than months ago\r\n* GI surgery (particularly when associated with delayed or incomplete healing) within days; Note: complete healing following abdominal surgery must be confirmed prior to initiating treatment with cabozantinib even if surgery occurred more than days ago Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders including:\r\n** Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within the last months:\r\n*** Unstable angina pectoris\r\n*** Clinically-significant cardiac arrhythmias\r\n*** Stroke (including TIA, or other ischemic event)\r\n*** Myocardial infarction\r\n*** Thromboembolic event requiring therapeutic anticoagulation; Note: subjects with a venous filter (e.g., vena cava filter) are not eligible for this study\r\n* Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n** Any of the following within days:\r\n*** Active peptic ulcer disease\r\n*** Active inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n*** Malabsorption syndrome\r\n** Any of the following within months:\r\n*** Abdominal fistula\r\n*** Gastrointestinal perforation\r\n*** Bowel obstruction or gastric outlet obstruction\r\n*** Intra-abdominal abscess; Note: complete resolution of an intra-abdominal abscess must be confirmed prior even if the abscess occurred more than months ago\r\n* Other disorders associated with a high risk of fistula formation or wound healing complications, including percutaneous endoscopic gastrostomy (PEG) tube placement within months\r\n* History of chronic pancreatitis Any of the following within months of registration: active peptic ulcer disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, malabsorption syndrome; any of the following within months of registration: intra-abdominal abscess, gastrointestinal obstruction requiring parenteral hydration and/or nutrition, gastrointestinal perforation; Note: complete resolution of an intra-abdominal abscess must be confirmed prior to registration even if the abscess occurred more than months prior to registration The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders:\r\n** Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias within weeks of enrollment\r\n** Uncontrolled hypertension defined as sustained blood pressure (BP) > mm Hg systolic or > mm Hg diastolic despite optimal antihypertensive treatment\r\n** Stroke (including transient ischemic attack), myocardial infarction, or other ischemic event within weeks of enrollment\r\n** Thromboembolic event (such as deep venous thrombosis, pulmonary embolism) within weeks of enrollment\r\n* Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:\r\n** Tumors invading the GI-tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction\r\n** Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within weeks before enrollment; note: complete healing of an intra-abdominal abscess must be confirmed before enrollment\r\n* Clinically significant hematuria, hematemesis, or hemoptysis of > . teaspoon (. ml) of red blood, or other history of significant bleeding (such as pulmonary hemorrhage) within weeks of enrollment\r\n* Other clinically significant disorders such as:\r\n** Active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or chronic hepatitis B or C infection\r\n** Serious non-healing wound or ulcer\r\n** Malabsorption syndrome\r\n** Symptomatic hypothyroidism\r\n** Moderate to severe hepatic impairment (Child-Pugh B or C)\r\n** Requirement for hemodialysis or peritoneal dialysis\r\n** History of solid organ transplantation Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n*Any of the following within days before the first dose of study treatment:\r\n** Intra-abdominal tumor/metastases invading gastro-intestinal mucosa\r\n** Active peptic ulcer disease\r\n** Inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n** Malabsorption syndrome\r\n* Any of the following within months before the first dose of study treatment:\r\n** Abdominal fistula\r\n** Gastrointestinal perforation\r\n** Bowel obstruction or gastric outlet obstruction\r\n** 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 than months before the first dose of study treatment The subject has uncontrolled or significant intercurrent illness including, but not limited to, the following conditions: \r\n* Chronically uncontrolled hypertension, defined conventionally as consistent and repeated systolic pressures above mmHg or diastolic pressures above mmHg despite anti-hypertensive therapy; this may be better established with home blood pressure (BP) readings than with clinic visit results; there is no criterion related to a specific BP result required for eligibility, nor are acute BP elevations that are related to iatrogenic causes, acute pain, or other transient reversible causes considered to be an exclusion criteria\r\n* Other cardiovascular disorders such as symptomatic congestive heart failure (CHF), unstable angina pectoris, clinically-significant cardiac arrhythmias, history of stroke (including transient ischemic attack [TIA], or other ischemic event) within months of study treatment, myocardial infarction within months of study treatment, history of thromboembolic event requiring therapeutic anticoagulation within months of study treatment or main portal vein or vena cava thrombosis or occlusion\r\n* Gastrointestinal (GI) disorders particularly those associated with a high risk of perforation or fistula formation including: Any of the following at the time of screening; a) intra-abdominal tumor/metastases invading GI mucosa b) active peptic ulcer disease, c) inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n* Any of the following within months before the first dose of study treatment: a) history of abdominal fistula b) gastrointestinal perforation c) bowel obstruction or gastric outlet obstruction; d) 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 than months ago; GI surgery (particularly when associated with delayed or incomplete healing) within days; Note: Complete healing following abdominal surgery must be confirmed prior to initiating treatment with cabozantinib even if surgery occurred more than days ago; other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within months before the first dose of study therapy or concurrent evidence of intraluminal tumor involving the trachea and esophagus The participant has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders including \r\n** Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening\r\n** Uncontrolled hypertension defined as sustained blood pressure (BP) > mm Hg systolic, or > mm Hg diastolic despite optimal antihypertensive treatment (BP must be controlled at screening)\r\n** Any of the following within months before the first dose of study treatment:\r\n*** Unstable angina pectoris\r\n*** Clinically-significant cardiac arrhythmias\r\n*** Stroke (including transient ischemic attack [TIA], or other ischemic event)\r\n*** Myocardial infarction\r\n*** Thromboembolic event requiring therapeutic anticoagulation (Note: participants with a venous filter [e.g. vena cava filter] are not eligible for this study)\r\n* Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n** Any of the following at the time of screening\r\n*** Intra-abdominal tumor/metastases invading gastrointestinal (GI) mucosa\r\n*** Active peptic ulcer disease\r\n*** Inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n** Any of the following within months before the first dose of study treatment:\r\n*** History of abdominal fistula\r\n*** Gastrointestinal perforation\r\n*** Bowel obstruction or gastric outlet obstruction\r\n*** 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 than months ago\r\n** GI surgery (particularly when associated with delayed or incomplete healing) within days; Note: complete healing following abdominal surgery must be confirmed prior to initiating treatment with cabozantinib even if surgery occurred more than days ago\r\n* Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within months before the first dose of study therapy or concurrent evidence of intraluminal tumor involving the trachea and esophagus\r\n* Other clinically significant disorders such as:\r\n** Active infection requiring systemic treatment\r\n** Serious non-healing wound/ulcer/bone fracture\r\n** History of organ transplant\r\n** Concurrent uncompensated hypothyroidism or thyroid dysfunction\r\n** History of major surgery within weeks or minor surgical procedures within week before randomization Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n* Any of the following that have not resolved within days before the first dose of study treatment\r\n** Intra-abdominal tumor/metastases invading GI mucosa\r\n** Active peptic ulcer disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n** Malabsorption syndrome\r\n* Any of the following within months before the first dose of study treatment:\r\n** Abdominal fistula\r\n** Gastrointestinal perforation\r\n** Bowel obstruction or gastric outlet obstruction\r\n** 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 than months before the first dose of study treatment Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n* Any of the following at the time of screening\r\n** Intra-abdominal tumor/metastases invading gastrointestinal (GI) mucosa\r\n** Active peptic ulcer disease\r\n** Inflammatory bowel disease (including ulcerative colitis and Crohns disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n* Any of the following within months before the first dose of study treatment:\r\n** History of abdominal fistula\r\n** Gastrointestinal perforation\r\n** Bowel obstruction or gastric outlet obstruction\r\n** 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 than months ago\r\n** Malabsorption syndrome\r\n* Percutaneous endoscopic gastrostomy (PEG) tube placement within months before the first dose of study therapy Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n* Any of the following at the time of screening:\r\n** Intra-abdominal tumor/metastases invading gastrointestinal (GI) mucosa\r\n** Active peptic ulcer disease\r\n** Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n** Malabsorption syndrome\r\n* Any of the following within months before the first dose of study treatment:\r\n** History of abdominal fistula\r\n** Gastrointestinal perforation\r\n** Bowel obstruction or gastric outlet obstruction\r\n** 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 than months ago Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n* Any of the following within days before the first dose of study treatment\r\n** Intra-abdominal tumor/metastases invading gastrointestinal (GI) mucosa (malignant abdominal ascites does not constitute mucosal invasion)\r\n** Active peptic ulcer disease\r\n** Inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n** Malabsorption syndrome\r\n* Any of the following within months before the first dose of study treatment:\r\n** History of abdominal fistula\r\n** Gastrointestinal perforation\r\n** Bowel obstruction or gastric outlet obstruction\r\n** 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 than months ago