Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis should be evaluated for the potential need for additional treatment before coming on study

Participants who have had evidence of Clostridium (C.) difficile infection, active or acute diverticulitis, intra-abdominal abscess, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis, which are known risk factors for bowel perforation, should be evaluated for the potential need for additional treatment before coming on study

Participants may not have had history of abdominal fistula or gastrointestinal perforation within the past 6 months

Participants may not have had a history of intra-abdominal abscess within the past 6 months

History of abdominal fistula, gastrointestinal perforation, peptic ulcer, or intra-abdominal abscess within 6 months

History of abdominal fistula, intra-abdominal abscess, or gastrointestinal perforation within the last 3 months

Gastrointestinal perforation or fistula in the 6 months prior to randomization unless underlying risk has been resolved (e.g., through surgical resection or repair)

No gastrointestinal disorders associated with a high risk of perforation or fistula formation within 6 months prior to registration:\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 6 months prior to registration

History of abdominal/pelvic or tracheoesophageal fistula or gastrointestinal perforation and/or abscess within 6 months prior to initiation of treatment

Subjects with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including:\r\n* Active peptic ulcer disease\r\n* Known intraluminal metastatic lesions\r\n* Inflammatory bowel disease (e.g., ulcerative colitis, Crohn’s disease) or other gastrointestinal conditions which increase the risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to beginning study treatment

Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment are NOT eligible for participation

Clinically significant gastrointestinal (GI) abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:\r\n* Active peptic ulcer disease\r\n* Known intraluminal metastatic lesion/s with risk of bleeding\r\n* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation \r\n* History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment\r\n* Clinically significant (> 1/2 teaspoon) hemoptysis or gastrointestinal hemorrhage in the past 6 months

History of abdominal fistula or gastrointestinal perforation within 6 months prior to day 1

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:\r\n* Active peptic ulcer disease\r\n* Known intraluminal metastatic lesion/s with risk of bleeding\r\n* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =< 28 days prior to randomization\r\n* Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:\r\n** Malabsorption syndrome\r\n** Any prior major resection of the stomach or small bowel

History of abdominal fistula, gastrointestinal perforation, pneumothorax, or intra-abdominal abscess within 28 days of study enrollment

History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, clinical signs or symptoms of gastrointestinaI obstruction or other known clinically signification gastrointestinal disease.

Acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction within the past 6 months.

History of gastrointestinal perforation within last 6 months.

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) > 150 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of cabozantinib\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within 6 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 28 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 Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis; malabsorption syndrome\r\n** Any of the following within 6 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 6 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 3 months before the first dose of study therapy\r\n* Other clinically significant disorders such as:\r\n** Active infection requiring systemic treatment within 28 days before the first dose of cabozantinib\r\n** Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of cabozantinib\r\n** History of organ transplant\r\n** Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of cabozantinib

Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug

No history of abdominal fistula, gastrointestinal (GI) perforation, intra abdominal abscess, uncontrolled GI bleeding, diverticulitis within 6 months of study entry

Patients with a history of abdominal or tracheal-esophageal fistula, or gastrointestinal perforation are not eligible; patients with a history of intra-abdominal abscess within 6 months of enrollment

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) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within 6 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, Crohn’s 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 6 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

Active inflammatory gastrointestinal disease, chronic diarrhea (unless related to underlying malignancy or prior related treatment) or history of abdominal fistula, gastrointestinal perforation, peptic ulcer disease, or intra-abdominal abscess within 6 months prior to study enrollment. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed.

history of abdominal fistula or gastrointestinal perforation

intra-abdominal abscess within last 3 months prior to the first dose of study drug

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of study enrollment.

Patients who have a history of fistula, gastrointestinal ulcer or perforation, or intra-abdominal abscess within 3 months of study enrollment are not eligible

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) > 140 mmHg systolic, or > 90 mmHg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within 6 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 28 days before the first dose of study treatment\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 6 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 6 months before the first dose of study treatment

No history of gastrointestinal fistula or gastrointestinal perforation < 90 days of registration

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization.

Active inflammatory gastrointestinal disease, chronic diarrhea (unless related to underlying malignancy or prior related treatment) or history of abdominal fistula, gastrointestinal perforation, peptic ulcer disease, or intra-abdominal abscess within 6 months prior to study enrollment. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed.

History of abdominal fistula or gastrointestinal perforation within 6 months prior to registration

History of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, or abdominal carcinomatosis.

History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to starting treatment

No myocardial infarction, gastrointestinal (GI) perforation/fistula, intraabdominal abscess, cerebrovascular accidents within six months prior to study entry

History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 1

Prior history of gastrointestinal diverticulitis, perforation, or abscess.

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 Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n** Any of the following within 6 months before the first dose of study treatment:\r\n*** History of abdominal fistula\r\n*** Bowel perforation

History of prior gastrointestinal fistula and/or perforation

Has a known history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to planned start of study drug

Any history of gastrointestinal (GI) perforation, history of intra-abdominal abscess within 3 months prior to starting treatment, or history of abdominal fistula unless the fistula history meets all the following: (a) the fistula was surgically repaired, (b) there has been no evidence of fistula for at least 6 months prior to starting treatment, (c) patient is deemed to be at low risk of recurrent fistula, and (d) the case must be discussed with the study PI

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 than 6 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 90 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) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment;\r\n** Any history of congenital long QT syndrome;\r\n** Any of the following within 6 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., Crohn’s 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 6 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, Crohn’s 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 6 months before randomization

History of gastrointestinal fistula, hemorrhage, perforation or peptic ulcer disease

Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection

Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, or abdominal carcinomatosis (known risks factors for bowel perforation)

Any of the following within 2 months of registration: active peptic ulcer disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, malabsorption syndrome; any of the following within 6 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 6 months prior to registration

Patients who have had a history of acute diverticulitis, abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis which are known risks factors for bowel perforation, should be excluded from the study

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) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal anti-hypertensive treatment within 7 days of the first dose of study treatment\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within 6 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., Crohn’s 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 6 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 6 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, Crohn’s 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 6 months before randomization,\r\n** Note: complete healing of an intra-abdominal abscess must be confirmed prior to randomization\r\n* Hemoptysis of >= 0.5 teaspoon (2.5ml) of red blood within 3 months before the first dose of study treatment;\r\n* Any other signs indicative of pulmonary hemorrhage within 3 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)

History of gastrointestinal perforation or fistula in the 6 months prior to study treatment, or while previously on antiangiogenic therapy, unless underlying risk has been resolved (e.g., through surgical resection or repair)

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) > 150 mm Hg systolic or > 100 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 3 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 6 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 > 0.5 teaspoon within 3 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

History of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months prior to enrollment

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:\r\n* Active peptic ulcer disease\r\n* Known intraluminal metastatic lesion(s) with risk of bleeding\r\n* Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions with increased risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment

Active inflammatory gastrointestinal disease, chronic diarrhea (unless related to underlying malignancy or prior related treatment) or history of abdominal fistula, gastrointestinal perforation, peptic ulcer disease, or intra-abdominal abscess within 6 months prior to study enrollment; gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed

History of acute diverticulitis, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.

History of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess within 28 days prior to registration.

Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study

Serious intercurrent illness such as:\r\n* Hypertension (two or more blood pressure readings performed at screening of > 150 mmHg systolic or > 100 mmHg diastolic) despite optimal treatment\r\n* Non-healing wound or ulcer\r\n* Uncontrolled life threatening cardiac arrhythmias\r\n* Untreated hypothyroidism\r\n* Uncontrolled active infection\r\n* Symptomatic congestive heart failure or unstable angina pectoris within 3 months prior to study drug\r\n* Myocardial infarction, stroke, transient ischemic attack within 6 months\r\n* Gastrointestinal perforation, abdominal fistula, intra-abdominal abscess within 1 year

Any of the following within 6 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 6 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) > 140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within 6 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 28 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 Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n*** Malabsorption syndrome\r\n** Any of the following within 6 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 6 months before the first dose of study treatment

History of abdominal or tracheoesophageal fistula or gastrointestinal (GI) perforation within 6 months of first study treatment

History of abdominal fistula, intra-abdominal abscess, or gastrointestinal perforation within the 3 months prior to enrollment

Any of the following conditions:\r\n* Active peptic ulcer disease\r\n* Inflammatory bowel disease (e.g., ulcerative colitis, Crohn’s disease) or other gastrointestinal conditions which increase the risk of perforation\r\n* History of new abdominal fistula, gastrointestinal perforation or intra-abdominal abscess =< 84 days prior to registration; NOTE: enrollment of patients with chronic/canalized fistulous tracts (present for > 84 days) is allowed\r\n* Serious or non-healing wound, ulcer, or bone fracture\r\n* History of familial QTc prolongation syndrome

Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis should be evaluated for the potential need for additional treatment before coming on study

Patients with active bleeding are not eligible; specifically, no clinically significant gastrointestinal (GI) bleeding, GI perforation, intra-abdominal abscess or fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary hemorrhage for 3 months prior to enrollment

Active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.

Patients who have had prior abdominal radiotherapy

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =< 6 months prior to registration

Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug

Patients who have had a history of illness which put them at current risk for bowel perforation such as acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis

History of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months prior to cycle 1, day 1

History of acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation

Active inflammatory gastrointestinal disease such as chronic diarrhea (unless related to underlying malignancy or prior related treatment) or history of abdominal fistula, gastrointestinal perforation, peptic ulcer disease, or intra-abdominal abscess within 6 months prior to study enrollment; gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed

Previous history of abdominal fistula, tracheoesophageal fistula or other fistula with grade 4 severity, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to enrollment

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) > 150 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within 6 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 28 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 Crohn’s 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 6 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 6 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 3 months before the first dose of study therapy \r\n* Other clinically significant disorders such as:\r\n** Active infection requiring systemic treatment within 28 days before the first dose of study treatment\r\n** Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment\r\n** History of organ transplant\r\n** Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment\r\n** History of major surgery as follows:\r\n*** Major surgery within 12 weeks before the first dose of study treatment; complete wound healing from major surgery must have occurred 1 month before the first dose of study treatment\r\n*** Minor surgery (including uncomplicated tooth extractions) within 28 days before the first dose of study treatment with complete wound healing at least 10 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 12 weeks before enrollment; NOTE: complete healing of an intra-abdominal abscess must be confirmed before enrollment

Any of the following within 28 days of first date of study treatment: \r\n* Serious uncontrolled medical illness or disorder that in the opinion of the treating physician would make the patient ineligible for the study\r\n* Active uncontrolled infection (with the exception of uncomplicated urinary tract infection) \r\n* Abdominal fistula, gastrointestinal perforation or intra-abdominal abscess\r\n* Abdominal surgery (for reasons other than IP port placement)

PHASE I STUDY ELIGIBILITY CRITERIA:\r\nHistory of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment

PHASE II STUDY COHORT 1 OVARIAN CANCER ELIGIBILITY CRITERIA (MEDI+O, MEDI+C AND MEDI+O+C):\r\nHistory of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment

PHASE II COLORECTAL CANCER COHORT 6 (MEDI+C ONLY):\r\nHistory of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment

History of gastrointestinal perforation; patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired or has healed, there has been no evidence of fistula for at least 6 months, and patient is deemed to be at low risk of recurrent fistula

History of intra-abdominal abscess within the past 3 months

Patients must be reasonable candidates for laparoscopy and IP platinum regimen with no prior evidence of clinically significant intra-abdominal adhesions, persistent abdominal wall infections, renal toxicity, or bowel obstruction

History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved (e.g., through surgical resection or repair)

Prior abdominal radiotherapy

History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within six months prior to treatment start

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 > 150 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment, iii. any history of congenital long QT syndrome, or iv. any of the following within 6 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 28 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 Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis (patient must be completely recovered from these conditions), malabsorption syndrome; ii. any of the following within 6 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 6 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 3 months before the first dose of study therapy, d. other clinically significant disorders such as: i. active infection requiring systemic treatment within 28 days before the first dose of study treatment, ii. serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment, iii. history of organ transplant, iv. concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment, or v. major surgery within 12 weeks before the first dose of study treatment; complete wound healing from major surgery must have occurred 1 month before the first dose of study treatment; minor surgery within 28 days before the first dose of study treatment with complete wound healing at least 10 days before the first dose of study treatment; subjects with clinically relevant ongoing complications from prior surgery are not eligible

Active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation

History of abdominal fistula or gastrointestinal perforation =< 6 months prior to treatment with study drugs

Patients who have had a history of acute diverticulitis, abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal carcinomatosis which are known risks factors for bowel perforation, should be excluded from the study

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding, including (but not limited to) active peptic ulcer disease, known intraluminal metastatic lesions with risk of bleeding, inflammatory bowel disease (e.g., ulcerative colitis, Crohn’s disease) or other gastrointestinal (GI) conditions with increased risk of perforation, history of abdominal fistula or intra-abdominal abscess within 28 days prior to beginning study treatment

History of abdominal fistula or gastrointestinal perforation =< 6 months prior to treatment with study drugs

History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days or manifestations of malabsorption due to prior gastrointestinal (GI) surgery or GI disease that may alter the absorption of MLN0128 (TAK-228)

Gastrointestinal perforation or intra-abdominal abscess (< 3 months); recent (< 3 months) gastrointestinal (GI) bleeding from gastric or duodenal ulcer

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) > 140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within 6 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 28 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 Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n*** Malabsorption syndrome\r\n** Any of the following within 6 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 6 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 3 months before the first dose of study therapy\r\n* Other clinically significant disorders such as:\r\n** Serious active infection requiring systemic treatment within 28 days before the first dose of study treatment\r\n** Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment\r\n** History of organ transplant\r\n** Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment\r\n** History of surgery as follows:\r\n*** Subjects having undergone recent resection or biopsy of an intracranial tumor will be eligible as long as all of the following conditions apply: First dose of cabozantinib occurs at least 28 days after surgery, and the subject has recovered from the effects of surgery\r\n*** Other minor surgery within 28 days of the first dose of cabozantinib if there were no wound healing complications. If there is evidence of wound dehiscence, subjects will be eligible for trial after a minimum of 3 months after surgery to the first dose of cabozantinib, provided complete wound healing is confirmed at least 28 days before the first dose of cabozantinib\r\n*** Other major surgery within 2 months of the first dose of cabozantinib if there were no wound healing complications; if there is evidence of wound dehiscence, subjects will be eligible for trial after a minimum of 6 months after surgery to the first dose of cabozantinib, provided complete wound healing in confirmed at least 28 days before the first dose of cabozantinib

History of abdominal fistula or gastrointestinal perforation within 6 months prior to day 1

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) > 140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within 6 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 28 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 Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n*** Malabsorption syndrome\r\n** Any of the following within 6 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 6 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 3 months before the first dose of study therapy\r\n* Other clinically significant disorders such as:\r\n** Active infection requiring systemic treatment within 28 days before the first dose of study treatment\r\n** Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment\r\n** History of organ transplant\r\n** Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment\r\n** History of major surgery as follows:\r\n*** 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\r\n*** 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; in addition complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery

Patients with peptic ulcer, abdominal fistula, gastrointestinal perforation, intra-abdominal abscess within 6 months of registration

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 1

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0

History of abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months of randomization

History of acute diverticulitis, intra-abdominal abscess, GI obstruction, abdominal carcinomatosis or other known risk factors for bowel perforation.

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: \r\n* Active peptic ulcer disease \r\n* Known intraluminal metastatic lesion/s with risk of bleeding \r\n* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn‘s disease), or other gastrointestinal conditions with increased risk of perforation \r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment

History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 1

Gastrointestinal (GI) perforation/fistula

History of abdominal fistula or gastrointestinal perforation within 6 months prior to day 1 of FOLFIRI + bevacizumab initiation

History of an abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within previous 6 months

History of abdominal fistula or gastrointestinal perforation within 6 months prior to randomization

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 1 of study drug

Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.

History of gastrointestinal perforation and /or fistula or aorto-esophageal fistula within 6 months prior to randomization

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:\r\n* Active peptic ulcer disease\r\n* Known intraluminal metastatic lesion/s with risk of bleeding\r\n* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =< 28 days prior to registration\r\n* Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:\r\n** Malabsorption syndrome\r\n** Major resection of the stomach or small bowel

Subjects who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation.

Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, and gastrointestinal (GI) obstruction which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study

Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study

Active diverticulitis, intra-abdominal abscess or gastrointestinal (GI) obstruction

History of gastrointestinal perforation, abscess or fistula

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) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment;\r\n** Any history of congenital long QT syndrome;\r\n** Any of the following within 6 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, Crohn’s 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 6 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

History of abdominal fistula formation, gastrointestinal perforation, or abdominal abscess within six months

Patient history:\r\n* Patients with history of neurofibromatosis (NF) may have other stable central nervous system (CNS) tumors (schwannoma, acoustic neuroma or ependymoma) if lesions have been stable for 6 months\r\n* No metastatic meningiomas (as defined by extracranial meningiomas) allowed\r\n* No history of allergic reactions attributed to compounds of similar or biologic composition to assigned study drug\r\n* No known active hepatitis B or C\r\n* No current Child Pugh class B or C liver disease\r\n* No uncontrolled gastric ulcer disease (grade 3 gastric ulcer disease within 28 days of registration)\r\n* No uncontrolled diabetes defined as a known diabetic with hemoglobin A1C (HBA1C) > 7.5 OR fasting glucose > 140\r\n* No uncontrolled hypertension defined as blood pressure (BP) > 140/90\r\n* No abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 28 days prior to registration

Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n* Any of the following within 28 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 Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n** Malabsorption syndrome\r\n* Any of the following within 6 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 6 months before the first dose of study treatment

Patients with clinically significant gastrointestinal abnormalities including, but not limited to:\r\n* Clinically significant signs and/or symptoms of bowel obstruction within 3 months prior to starting treatment\r\n* History of intra-abdominal abscess within 3 months prior to starting treatment\r\n* History of gastrointestinal (GI) perforation within 6 months prior to starting treatment\r\n* Evidence of abdominal fistula within 6 months prior to starting treatment; history of abdominal fistula will be considered eligible if the fistula was surgically repaired, and there has been no evidence of fistula for at least 6 months prior to starting treatment, and patient is deemed to be at low risk of recurrent fistula

The following are additional exclusion criteria for patients enrolling in expansion cohort C:\r\n* Uncontrolled blood pressure (> 140/90); patients should have a blood pressure of =< 140/90 taken by a medical professional within one week of starting on study\r\n* Proteinuria > 2+ 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 28 days of registration\r\n** Inflammatory bowel disease (including ulcerative colitis and Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis, or appendicitis\r\n* Any of the following within 6 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 6 months prior to registration\r\n* Major surgery within 3 months of the first dose of study drugs if there were no wound healing complications or within 6 months of the first dose of study drugs if there were wound complications

History of intra-abdominal abscess within the past 3 months

History of gastrointestinal perforation; patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired or has healed, there has been no evidence of fistula for at least 6 months, and patient is deemed to be at low risk of recurrent fistula

Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, fistula and abdominal carcinomatosis should be evaluated for the potential need for additional treatment before coming on study

History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1

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* Any of the following within 6 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 6 months ago\r\n* GI surgery (particularly when associated with delayed or incomplete healing) within 28 days; Note: complete healing following abdominal surgery must be confirmed prior to initiating treatment with cabozantinib even if surgery occurred more than 28 days ago

No evidence of a bowel obstruction, abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of study entry

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess in previous 6 months

Patients at significant risk for GI perforation or fistula

Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study

Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, abdominal/pelvic fistula, gastrointestinal perforation, gastrointestinal (GI) obstruction and/or who require parenteral hydration and/or nutrition

Patients who have a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of study enrollment are not eligible

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 1

Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study

The patient may not have 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) > 140 mmHg systolic, or > 90 mmHg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within 24 weeks 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: patients 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 28 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 Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n*** Malabsorption syndrome\r\n** Any of the following within 24 weeks 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 that 24 weeks before the first dose of study treatment\r\n*** Bowel obstruction or gastric outlet obstruction\r\n* Other clinically significant disorders such as:\r\n** Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment\r\n** History of organ transplant\r\n** Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment\r\n** History of major surgery as follows:\r\n*** Major surgery in past 8 weeks of the first dose of cabozantinib if there were no wound healing complications or within 24 weeks of the first dose of cabozantinib if there were wound complications\r\n*** Minor surgery within 4 weeks of the first dose of cabozantinib if there were no wound healing complications or within 12 weeks of the first dose of cabozantinib if there were wound complications\r\n*** In addition, complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery\r\n** Active infection requiring systemic treatment within 28 days before the first dose of study treatment

Subjects with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including\r\n* Active peptic ulcer disease\r\n* Known intraluminal metastatic lesions\r\n* Inflammatory bowel disease (e.g., ulcerative colitis, Crohn’s disease) or other gastrointestinal conditions which increase the risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to beginning study treatment

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 1 of treatment

Patients with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including:\r\n* Active peptic ulcer disease\r\n* Known intraluminal metastatic lesions\r\n* Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment

Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment

The participant has a history of gastrointestinal perforation or fistula within 6 months.

Patients must not have an acute or subacute intestinal obstruction; no history of bowel obstruction, gastrointestinal (GI) perforation, major abdominal surgery with bowel resection, or perirectal/perianal abscess within 6 months prior to randomization

History of abdominal fistula or gastrointestinal perforation at any point within 6 months prior to day 1 of study drug, unless surgically repaired

Patients with serious non-healing wound, ulcer, or bone fracture; this includes history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to the first date of study treatment; Note: Deliberate surgically created abdominal fistula is acceptable

Patients may not have a prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors of perforation

Patient must have no history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to randomization

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:\r\n* Active peptic ulcer disease\r\n* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding, including (but not limited to) active peptic ulcer disease, known intraluminal metastatic lesions with risk of bleeding, inflammatory bowel disease (e.g., ulcerative colitis, Crohn’s disease) or other gastrointestinal (GI) conditions with increased risk of perforation, history of abdominal fistula or intra-abdominal abscess within 28 days prior to beginning study treatment

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 6 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 28 days:\r\n*** Active peptic ulcer disease\r\n*** Active 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 6 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 6 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 3 months\r\n* History of chronic pancreatitis

History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved (e.g., through surgical resection or repair)

No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 12 months

Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, peritoneal carcinomatosis.

Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other Gastrointestinal conditions with increased risk of perforation; history of abdominal fistula, GI perforation, or intra-abdominal abscess within 4 weeks before beginning study treatment

Patients are excluded if they have history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization

History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months prior to Day 1.

Subjects with a history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess; clinical signs or symptoms of GI obstruction and/or requirement for parenteral hydration or nutrition. In addition, subjects with other known clinically significant gastrointestinal disease including, but not limited to, inflammatory bowel disease.

Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, or abdominal carcinomatosis (known risks factors for bowel perforation)

History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved (e.g., through surgical resection or repair)

History of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months prior to cycle 1, day 1

History of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess; evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction

Any of the following within 2 months of registration: active peptic ulcer disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, malabsorption syndrome; any of the following within 6 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 6 months prior to registration

Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection

History of abdominal fistula or gastrointestinal perforation at any point within 6 months prior to day 1 of study drug, unless surgically repaired

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) > 150 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment (BP must be controlled at screening)\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within 6 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* Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n** Any of the following within 28 days before the first dose of cabozantinib:\r\n*** Active peptic ulcer disease\r\n*** Active inflammatory bowel disease (including ulcerative colitis and Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n*** Active malabsorption syndrome\r\n** Any of the following within 6 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 6 months ago\r\n*** Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy\r\n* Other clinically significant disorders such as:\r\n** No active systemic infection requiring parenteral antibiotics\r\n** Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment\r\n** History of organ transplant\r\n** Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment\r\n** History of major surgery as follows:\r\n*** 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\r\n*** 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\r\n*** In addition, complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery

Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection

Patients with a history of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to Day 0

Patients with a history of abdominal fistula or gastrointestinal (GI) perforation within 6 months prior to registration are not eligible

Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, or abdominal carcinomatosis (known risks factors for bowel perforation)

History of intra-abdominal abscess within 3 months prior to starting treatment

History of GI perforation. Patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired, there has been no evidence of fistula for at least 6 months prior to starting treatment, and patient is deemed to be at low risk of recurrent fistula

Clinically active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, or abdominal carcinomatosis (known risks factors for bowel perforation)

History of abdominal/pelvic fistula, gastrointestinal perforation and/or intraabdominal abscess within 6 months prior to day 1

Participants may not have evidence of a bowel obstruction, abdominal fistula, or intra-abdominal abscess within 6 months of study entry; participants with current signs or symptoms suggestive of bowel obstruction including early or partial obstruction are ineligible; participants with a history of gastrointestinal perforation at any time point are ineligible

History of intra-abdominal abscess =< 6 months prior to randomization; Note: if the affected area was surgically resected, and there is no further risk to the area, patients may enroll

History of abdominal or other significant fistula, gastrointestinal or other organ perforation; Note: if the affected area was surgically resected, and there is no further risk to the area, patients may enroll

Have a history of gastrointestinal perforation and/or fistula within 6 months prior to enrollment.

Patient has risk factors for bowel obstruction or bowel perforation (examples include but not limited to a history of acute diverticulitis, intra-abdominal abscess, and abdominal carcinomatosis)

The participant has a history of gastrointestinal perforation or fistula within 6 months prior to randomization.

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 12 weeks of enrollment\r\n** Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment\r\n** Stroke (including transient ischemic attack), myocardial infarction, or other ischemic event within 12 weeks of enrollment\r\n** Thromboembolic event (such as deep venous thrombosis, pulmonary embolism) within 4 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 12 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 > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (such as pulmonary hemorrhage) within 4 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

Participants may not have had history of abdominal fistula or gastrointestinal perforation; patients with a history of abdominal fistula will be considered eligible if the fistula has healed or was surgically repaired, there has been no evidence of fistula for at least 6 months, and patient is deemed to be at low risk of recurrent fistula

Participants may not have had a history of intra-abdominal abscess within the past 3 months

The subject has serious intercurrent illness, such as:\r\n* Hypertension (two or more blood pressure [BP] readings performed at screening of > 150 mmHg systolic or > 100 mmHg diastolic) despite optimal treatment\r\n* Non-healing wound, ulcer, or bone fracture\r\n* Significant cardiac arrhythmias\r\n* Untreated hypothyroidism\r\n* Uncontrolled active infection\r\n* Symptomatic congestive heart failure or unstable angina pectoris within 3 months prior study drug\r\n* Myocardial infarction, stroke, transient ischemic attack within 6 months\r\n* Gastrointestinal perforation, abdominal fistula, intra-abdominal abscess within 1 year\r\n* History or clinical evidence of pancreatitis within 2 years

Evidence of active or acute (i.e. current, or recent within 4 weeks prior to registration) diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation; patients with abdominal carcinomatosis, a history of non-recent intra-abdominal abscess, or a history of non-recent GI obstruction should be evaluated for the potential need for additional treatment before coming on study

Has a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to start of study drug

History of gastrointestinal perforation =< 12 months prior to randomization

Patients will be excluded if they have had a major resection of the bowel that could influence absorption, inflammatory bowel disease, or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation within 28 days prior to beginning study treatment

Patients who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation

Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n*Any of the following within 28 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 Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n** Malabsorption syndrome\r\n* Any of the following within 6 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 6 months before the first dose of study treatment

History of abdominal fistula, gastrointestinal perforation, peptic ulcer, or intra-abdominal abscess within 6 months

COHORT A: Patients who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis

COHORT B: Patients who have had a history of acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:\r\n* Active peptic ulcer disease\r\n* Known intraluminal metastatic lesion/s with risk of bleeding\r\n* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment

Patients with the risk factors for bowel obstruction or bowel perforation (examples include but not limited to a history of acute diverticulitis, intra-abdominal abscess, abdominal carcinomatosis).

Patients who have had prior abdominal radiotherapy

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: \r\n* Active peptic ulcer disease \r\n* Known intraluminal metastatic lesion/s with risk of bleeding \r\n* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation \r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment

Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the previous 6 months are not eligible for participation

Active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal condition with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 4 weeks prior to administration of first dose of study drug

No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to registration

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: active peptic ulcer disease, known intraluminal metastatic lesion/s with risk of bleeding, Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation, history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment

History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to day 1

Patient must not have any clinically significant gastrointestinal abnormality that may increase the risk of gastrointestinal (GI) bleeding including, but not limited to, active peptic ulcer disease, known intraluminal metastatic lesions with risk of bleeding, inflammatory bowel disease (e.g., ulcerative colitis, Crohn’s disease), other GI conditions with increased risk of perforation, history of abdominal fistula or GI perforation or intra-abdominal abscess within 28 days prior to beginning 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) > 140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment (BP must be controlled at screening)\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within 6 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 28 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 Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n*** Malabsorption syndrome\r\n** Any of the following within 6 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 6 months ago\r\n* Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 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 intravenous treatment within 10 days of starting protocol treatment\r\n** Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment\r\n** History of organ transplant\r\n** Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment\r\n** History of major surgery as follows:\r\n*** 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\r\n*** 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\r\n*** In addition, complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery

History of gastrointestinal (GI) perforation within 5 years or patient has a current or prior intestinal fistula

History of bowel obstruction, including sub-occlusive disease, related to the underlying disease and history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess; evidence of recto sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction

No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to enrollment

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 140 mmHg or diastolic pressures above 90 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 6 months of study treatment, myocardial infarction within 6 months of study treatment, history of thromboembolic event requiring therapeutic anticoagulation within 6 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 Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n* Any of the following within 6 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 6 months ago; GI surgery (particularly when associated with delayed or incomplete healing) within 28 days; Note: Complete healing following abdominal surgery must be confirmed prior to initiating treatment with cabozantinib even if surgery occurred more than 28 days ago; other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy or concurrent evidence of intraluminal tumor involving the trachea and esophagus

Patients who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:\r\n* Active peptic ulcer disease\r\n* Known intraluminal metastatic lesion/s with risk of bleeding\r\n* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation \r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to registration

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) > 140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment (BP must be controlled at screening)\r\n** Any of the following within 6 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 Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n** Any of the following within 6 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 6 months ago\r\n** GI surgery (particularly when associated with delayed or incomplete healing) within 28 days; Note: complete healing following abdominal surgery must be confirmed prior to initiating treatment with cabozantinib even if surgery occurred more than 28 days ago\r\n* Other disorders associated with a high risk of fistula formation including percutaneous endoscopic gastrostomy (PEG) tube placement within 3 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 4 weeks or minor surgical procedures within 1 week before randomization

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:\r\n* Active peptic ulcer disease\r\n* Known intraluminal metastatic lesion/s with risk of bleeding\r\n* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment

History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess =< 6 months prior to randomization

History of abdominal fistula or gastrointestinal perforation within 6 months prior to day 1

History of abdominal fistula or gastrointestinal perforation within 6 months prior to day -3

Patients with symptoms of partial or complete bowel obstruction and recent (within 6 month) history of fistula, intra-abdominal abscess or bowel perforation

Clinically significant gastrointestinal abnormalities which might interfere with oral dosing, including, but not limited to:\r\n* Malabsorption syndrome\r\n* Major resection of the stomach or small bowel that could affect the absorption of study drug\r\n* Inflammatory bowel disease\r\n* Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment

History of abdominal fistula, gastrointestinal perforation, bowel obstruction, gastric outlet obstruction, or intra-abdominal abscess within six months of study enrollment

Subjects with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including\r\n* Active peptic ulcer disease, not on a proton pump inhibitor\r\n* Known intraluminal metastatic lesions\r\n* Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or \r\n* Other gastrointestinal conditions which increase the risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 28 days prior to beginning study treatment

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: \r\n* Active peptic ulcer disease\r\n* Known intraluminal metastatic lesion/s with risk of bleeding\r\n* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment

Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study registration

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:\r\n* Active peptic ulcer disease\r\n* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment\r\n* Clinically significant hemoptysis or gastrointestinal hemorrhage in the past 6 months

Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to planned day 1 of dosing are ineligible

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study entry

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal (GI) bleeding including, but not limited to: \r\n* Active peptic ulcer disease; \r\n* Known intraluminal metastatic lesion/s with suspected bleeding; \r\n* Inflammatory bowel disease; \r\n* Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation; \r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1

Subjects with a History of bowel obstruction, including sub?occlusive disease, related to the underlying\r\ndisease and history of abdominal fistula, gastrointestinal perforation or intra?abdominal abscess

Has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, and/or abdominal carcinomatosis

History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess within 6 months of enrollment.

Ongoing bowel perforation or presence of bowel fistula or abscess within 3 months of registration

History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess

History of abdominal fistula or gastrointestinal perforation =< 6 months prior to treatment with study drugs

History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1

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) > 140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days before the first dose of study treatment\r\n** Any history of congenital long QT syndrome\r\n** Any of the following within 6 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 28 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 Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis\r\n*** Malabsorption syndrome\r\n** Any of the following within 6 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 6 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 3 months before the first dose of study therapy \r\n* Other clinically significant disorders such as:\r\n** Active infection requiring systemic treatment within 28 days before the first dose of study treatment\r\n** Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment\r\n** History of organ transplant\r\n** Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment\r\n** History of major surgery as follows:\r\n*** 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\r\n*** 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\r\n*** Complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery

SUNITINIB MALATE ARM: Patients with any of the following conditions are excluded:\r\n* Serious or non-healing wound, ulcer, or bone fracture\r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment\r\n* Any history of cerebrovascular accident (CVA) or transient ischemic attack within 12 months prior to study entry\r\n* History of myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic congestive heart failure, or coronary/peripheral artery bypass graft or stenting within 12 months prior to study entry\r\n* History of pulmonary embolism within the past 12 months

Patients who have had prior abdominal radiotherapy

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 28 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 6 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 6 months before the first dose of study treatment

Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, GI obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study

Patients who have intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation

Patients who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation

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* Any of the following within 6 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 6 months ago\r\n** Malabsorption syndrome\r\n* Percutaneous endoscopic gastrostomy (PEG) tube placement within 3 months before the first dose of study therapy

At a higher than average risk, in the Investigator's opinion, of bowel perforation (e.g., symptoms of partial or complete bowel obstruction, recent (within 6 months) history of fistula or bowel perforation, requirement for total parenteral nutrition and continuous hydration)

Abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months

History of intra-abdominal inflammatory process within 6 months prior to Day 1 of Cycle 1 including but not limited to peptic ulcer disease, diverticulitis, or colitis

History of abdominal or tracheo-oesophageal fistula or gastrointestinal (GI) perforation or intra abdominal abscess within 6 months prior to Day 1 of Cycle 1

Patients who have had a history of acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis

History of abdominal fistula or gastrointestinal perforation

Patients with an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months

Conditions likely to increase the potential for abdominal perforation or fistula formation, including but not limited to: Luminal intestinal cancers or bulky abdominal disease. Presence or history of abdominal fistula, gastrointestinal perforation, peptic ulcer disease or intra-abdominal abscess within the six months prior to the first dose of GSK3052230. Other risk factors for perforation, such as acute diverticulitis, obstruction or previous abdominal or pelvic radiation.

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 6 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 6 months ago

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess =< 6 months prior to registration

Active peptic ulcer disease or history of abdominal fistula, GI perforation, or intra abdominal abscess within 28 days prior to enrolment

Evidence of abdominal fistula, gastrointestinal (GI) perforation or intraabdominal abscess

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 BP > 140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment \r\n** Any history of congenital long QT syndrome \r\n** Any of the following within 6 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 28 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 Crohn’s disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis \r\n*** Malabsorption syndrome \r\n** Any of the following within 6 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 6 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 3 months before the first dose of study therapy \r\n* Other clinically significant disorders such as: \r\n** Serious non-healing wound/ulcer/bone fracture within 28 days before the first dose of study treatment \r\n** History of organ transplant, including allogeneic bone marrow transplant \r\n** Concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment \r\n** History of major surgery as follows:\r\n*** 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 \r\n*** Minor surgery within 1 month 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 \r\n** In addition, complete wound healing from prior surgery must be confirmed at least 28 days before the first dose of cabozantinib irrespective of the time from surgery

Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including:\r\n* Any of the following within 28 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 6 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 6 months ago

Patients with any of the following conditions are excluded: serious or non-healing wound, ulcer; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment; coronary/peripheral artery bypass graft or stenting within the past 12 months; or cerebrovascular accident (CVA) or transient ischemic attack within the past 12 months

History of bowel obstruction, including sub-occlusive disease, related to the underlying disease or history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscesses. Evidence of rectosigmoid involvement by pelvic examination or bowel involvement on computed tomography (CT) scan or clinical symptoms of bowel obstruction.

Prior abdominal radiotherapy

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment

History of prior gastrointestinal perforation

Clinically significant gastrointestinal abnormalities including, but not limited to:\r\n* Malabsorption syndrome\r\n* Major resection of the stomach or small bowel that could affect the absorption of study drug\r\n* Active peptic ulcer disease\r\n* Inflammatory bowel disease\r\n* Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 0

History of an abdominal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within previous 6 months

History of complicated diverticulitis, including fistulae, abscess formation or gastrointestinal (GI) perforation

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: active peptic ulcer disease; known intraluminal metastatic lesion/s with risk of bleeding; inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment

Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding (e.g. active peptic ulcer, ulcerative colitis, Crohn’s disease, abdominal fistula) within prior 6 months

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to registration

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study screening

No history of gastrointestinal obstruction, or conditions that increase the risk of gastrointestinal obstruction, perforation, bleeding or impairment of the gastrointestinal wall; no abdominal surgery within 60 days of registration

No history of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 12 months

History of a gastrointestinal perforation

History of abdominal or tracheoesophageal fistula or gastrointestinal (GI) perforation within 6 months of first study treatment

Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction - Receipt of any live vaccine within 4 weeks.

History of abdominal fistula or gastrointestinal perforation within 6 months prior to day 1

History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months prior to Day 1

History of intra-abdominal inflammatory process within 6 months prior to Day 1 of Cycle 1

Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study

History of abdominal or tracheoesophageal fistula or gastrointestinal (GI) perforation within 6 months of first study treatment

Patients must not have known contraindications to bevacizumab, including but not limited to abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess, thrombotic or hemorrhagic disorders, uncontrolled hypertension or active clinically significant cardiovascular disease, non-healing wound, ulcer, or bone fracture within previous 4 weeks

Patients must not have clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:\r\n* Active peptic ulcer disease\r\n* Known intraluminal metastatic lesion/s with risk of bleeding \r\n* Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other gastrointestinal conditions with increased risk of perforation\r\n* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment

Patient must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess =< 6 months prior to study entry

Prior history of gastrointestinal (GI) perforation, diverticulitis, and/or peptic ulcer disease

Patients with active gastrointestinal disorders, those requiring procedures that pre-dispose to gastrointestinal (GI) perforation, those with a history of transmural inflammatory conditions, and/or history of gastrointestinal ulcers, strictures, obstructions, fistulae, and/or abscess will be excluded from the study due to the risk of serious and sometimes fatal gastrointestinal perforation

Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis which are known risk factors for bowel perforation should be evaluated for the potential need for additional treatment before coming on study

History of gastrointestinal perforation or fistula in the past 6 months, or while previously on antiangiogenic therapy, unless underlying risk has been resolved