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
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
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
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
Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:\r\n* Cardiovascular disorders:\r\n** Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mmHg systolic or > 90 mmHg diastolic despite optimal antihypertensive treatment\r\n** Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias\r\n** Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose\r\n* Any history of congenital long QT syndrome\r\n* Presence of a non-healing wound\r\n* Other clinically significant disorders that would preclude safe study participation including colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis, psychiatric conditions with active suicidal ideation within the past year; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Uncontrolled, significant concurrent 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 (BP) > 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) within 90 days of the first dose of study treatment, myocardial infarction, clinically significant thromboembolic event within 42 days of randomization requiring therapeutic anticoagulation.
(Note: subjects with a venous filter (e.g. vena cava filter) are not eligible for this study) b. gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including: i. any of the following within 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), acute pancreatitis, pancreatic duct or common bile duct obstruction, acute diverticulitis, acute cholecystitis, symptomatic cholangitis or recent appendicitis within 1 month of first dose of cabozantinib; patients must be completely recovered from these conditions, clinically significant malabsorption syndrome, c. endocrine disorders, uncontrolled Cushing syndrome despite of adequate medical therapy.
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
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
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
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
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
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
PHASE II STUDY METASTATIC CASTRATE-RESISTANT PROSTATE CANCER COHORT 4 ELIGIBILITY CRITERIA (MEDI+O ONLY):\r\nThe patient 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 anti-hypertensive 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 with the exception of asymptomatic atrial fibrillation controlled on therapy\r\n*** Stroke (including TIA, or other ischemic event)\r\n*** Myocardial infarction\r\n*** Thromboembolic event requiring therapeutic anti-coagulation (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)\r\n*** Mean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s correction or other significant ECG abnormality noted within 14 days of treatment\r\n* Other clinically significant disorders such as:\r\n** Active infection requiring intravenous treatment within 7 days of starting protocol treatment\r\n** Serious non-healing wound/ulcer/bone fracture (excluding stable compression fracture) within 28 days before the first dose of study treatment
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
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
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
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
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 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: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)
The subject has uncontrolled or significant intercurrent illness including, but not limited to,\r\nthe following conditions:\r\n* Cardiovascular disorders such as symptomatic congestive heart failure (CHF), uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic, or > 100 mm Hg diastolic despite optimal antihypertensive treatment (BP must be controlled at screening), 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; (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this 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
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
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
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
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
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 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)
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
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
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
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
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
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 (Note: if there is any BP measurement that is performed within the screening period that is < 150 mm Hg systolic and < 90 mm Hg diastolic, then BP does not meet definition of sustained)\r\n* Any congenital history of 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)