Trial Outcomes & Findings for Study of XL184 (Cabozantinib) in Adults With Glioblastoma Multiforme (NCT NCT00704288)
NCT ID: NCT00704288
Last Updated: 2024-02-05
Results Overview
Response and progression were determined per modified MacDonald Criteria and modified RANO criteria for GBM using imaging and clinical features
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
222 participants
Primary outcome timeframe
8 weeks until progressive disease
Results posted on
2024-02-05
Participant Flow
Participant milestones
| Measure |
Treatment Group A (175 mg)
Cabozantinib 175 mg (L-malate salt weight; 140 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group B (125 mg)
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group C (125 mg)
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
|---|---|---|---|
|
Overall Treatment Period
STARTED
|
46
|
59
|
117
|
|
Overall Treatment Period
Naïve
|
34
|
37
|
81
|
|
Overall Treatment Period
Pre-treated
|
12
|
22
|
36
|
|
Overall Treatment Period
COMPLETED
|
0
|
0
|
0
|
|
Overall Treatment Period
NOT COMPLETED
|
46
|
59
|
117
|
|
Extended Post Treatment Follow Up Period
STARTED
|
46
|
59
|
117
|
|
Extended Post Treatment Follow Up Period
COMPLETED
|
0
|
0
|
0
|
|
Extended Post Treatment Follow Up Period
NOT COMPLETED
|
46
|
59
|
117
|
Reasons for withdrawal
| Measure |
Treatment Group A (175 mg)
Cabozantinib 175 mg (L-malate salt weight; 140 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group B (125 mg)
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group C (125 mg)
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
|---|---|---|---|
|
Overall Treatment Period
Adverse Event
|
11
|
8
|
22
|
|
Overall Treatment Period
Death
|
0
|
0
|
1
|
|
Overall Treatment Period
Physician Decision
|
0
|
2
|
0
|
|
Overall Treatment Period
Withdrawal by Subject
|
0
|
1
|
3
|
|
Overall Treatment Period
Disease progression--per Modified MacDonald Criteria (Group A)
|
30
|
0
|
0
|
|
Overall Treatment Period
Disease Progression--Radiologic Progression (Group B and C)
|
0
|
42
|
76
|
|
Overall Treatment Period
Disease Progression--Clinical Deterioration
|
3
|
6
|
11
|
|
Overall Treatment Period
Roll-over to another study
|
1
|
0
|
4
|
|
Overall Treatment Period
Other--Subject had intracranial hemorrhage
|
1
|
0
|
0
|
|
Extended Post Treatment Follow Up Period
Death
|
41
|
50
|
93
|
|
Extended Post Treatment Follow Up Period
Lost to Follow-up
|
0
|
2
|
1
|
|
Extended Post Treatment Follow Up Period
Withdrawal by Subject
|
0
|
2
|
2
|
|
Extended Post Treatment Follow Up Period
Various reasons
|
5
|
5
|
21
|
Baseline Characteristics
Study of XL184 (Cabozantinib) in Adults With Glioblastoma Multiforme
Baseline characteristics by cohort
| Measure |
Treatment Group A (175 mg)
n=46 Participants
Cabozantinib 175 mg (L-malate salt weight; 140 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group B + Group C (125 mg)
n=176 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Total
n=222 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
18 to <45
|
11 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
44 Participants
n=5 Participants
|
|
Age, Customized
45 to <55
|
11 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
64 Participants
n=5 Participants
|
|
Age, Customized
55 to <65
|
18 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
|
Age, Customized
65 to <75
|
6 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
|
Age, Customized
>= 75
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
83 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
108 Participants
n=7 Participants
|
139 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
40 Participants
n=5 Participants
|
158 Participants
n=7 Participants
|
198 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 8 weeks until progressive diseaseResponse and progression were determined per modified MacDonald Criteria and modified RANO criteria for GBM using imaging and clinical features
Outcome measures
| Measure |
Treatment Group A1 (175 mg) - Naive
n=34 Participants
Cabozantinib 175 mg (L-malate salt weight; 140 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group B1 (125 mg) - Naive
n=37 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group C1 (125 mg) - Naive
n=80 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group A2 (175 mg) - Pre-Treated
n=12 Participants
Cabozantinib 175 mg (L-malate salt weight; 140 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group B2 (125 mg) - Pre-Treated
n=22 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group C2 (125 mg) - Pre-Treated
n=36 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
|---|---|---|---|---|---|---|
|
Objective Response Rate (ORR)
|
17.6 percentage of participants
|
27.0 percentage of participants
|
8.8 percentage of participants
|
8.3 percentage of participants
|
0 percentage of participants
|
5.6 percentage of participants
|
SECONDARY outcome
Timeframe: Assessed during periodically scheduled visits until progressive diseasePopulation: Insufficient number of participants with events
Duration of response is defined as the time from the first documentation of objective response that was subsequently confirmed at a visit that was ≥ 28 days later to disease progression or death due to any cause.
Outcome measures
| Measure |
Treatment Group A1 (175 mg) - Naive
n=6 Participants
Cabozantinib 175 mg (L-malate salt weight; 140 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group B1 (125 mg) - Naive
n=10 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group C1 (125 mg) - Naive
n=7 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group A2 (175 mg) - Pre-Treated
n=1 Participants
Cabozantinib 175 mg (L-malate salt weight; 140 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group B2 (125 mg) - Pre-Treated
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group C2 (125 mg) - Pre-Treated
n=2 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
|---|---|---|---|---|---|---|
|
Duration of Objective Response (Months)
|
5.913 Months
Interval 2.76 to 12.812
|
8.541 Months
Interval 3.778 to 9.264
|
NA Months
Interval 2.792 to
Median duration of response and its 95% CI upper limit are not estimable due to insufficient number of events and/or follow up
|
NA Months
Insufficient number of participants with events
|
—
|
4.172 Months
Insufficient number of participants with events
|
SECONDARY outcome
Timeframe: Assessed during periodically scheduled visits until progressive diseaseResponse and progression were determined per modified MacDonald Criteria and modified RANO criteria for GBM using imaging and clinical features
Outcome measures
| Measure |
Treatment Group A1 (175 mg) - Naive
n=34 Participants
Cabozantinib 175 mg (L-malate salt weight; 140 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group B1 (125 mg) - Naive
n=37 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group C1 (125 mg) - Naive
n=81 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group A2 (175 mg) - Pre-Treated
n=12 Participants
Cabozantinib 175 mg (L-malate salt weight; 140 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group B2 (125 mg) - Pre-Treated
n=22 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group C2 (125 mg) - Pre-Treated
n=36 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
|---|---|---|---|---|---|---|
|
Progression Free Survival (PFS)
|
3.712 Months
Interval 1.905 to 5.092
|
4.698 Months
Interval 3.647 to 9.231
|
3.712 Months
Interval 2.562 to 3.712
|
3.285 Months
Interval 0.953 to
Insufficient number of participants with events
|
1.807 Months
Interval 1.675 to 3.745
|
2.300 Months
Interval 2.201 to 2.464
|
SECONDARY outcome
Timeframe: Assessed during periodically scheduled visits until progressive diseaseOverall survival (OS) is defined as the time from first dose to death due to any cause.
Outcome measures
| Measure |
Treatment Group A1 (175 mg) - Naive
n=34 Participants
Cabozantinib 175 mg (L-malate salt weight; 140 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group B1 (125 mg) - Naive
n=12 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group C1 (125 mg) - Naive
n=37 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group A2 (175 mg) - Pre-Treated
n=22 Participants
Cabozantinib 175 mg (L-malate salt weight; 140 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group B2 (125 mg) - Pre-Treated
n=81 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group C2 (125 mg) - Pre-Treated
n=36 Participants
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
|---|---|---|---|---|---|---|
|
Overall Survival (OS)
|
7.671 Months
Interval 5.913 to 13.502
|
4.074 Months
Interval 1.38 to 16.689
|
10.381 Months
Interval 7.26 to 16.393
|
4.221 Months
Interval 1.971 to 5.716
|
10.217 Months
Interval 8.016 to 12.122
|
4.583 Months
Interval 2.792 to 5.683
|
Adverse Events
Treatment Group A (175 mg)
Serious events: 24 serious events
Other events: 46 other events
Deaths: 41 deaths
Treatment Group B + Group C (125 mg)
Serious events: 90 serious events
Other events: 176 other events
Deaths: 144 deaths
Serious adverse events
| Measure |
Treatment Group A (175 mg)
n=46 participants at risk
Cabozantinib 175 mg (L-malate salt weight; 140 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group B + Group C (125 mg)
n=176 participants at risk
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/46
|
2.3%
4/176
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/46
|
0.57%
1/176
|
|
Cardiac disorders
Acute Myocardial Infarction
|
0.00%
0/46
|
1.1%
2/176
|
|
Cardiac disorders
Cardiac Arrest
|
0.00%
0/46
|
0.57%
1/176
|
|
Cardiac disorders
Myocarditis
|
2.2%
1/46
|
0.00%
0/176
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/46
|
0.57%
1/176
|
|
Endocrine disorders
Hypothyroidism
|
0.00%
0/46
|
0.57%
1/176
|
|
Gastrointestinal disorders
Nausea
|
4.3%
2/46
|
1.7%
3/176
|
|
Gastrointestinal disorders
Diarrhoea
|
6.5%
3/46
|
1.1%
2/176
|
|
Gastrointestinal disorders
Vomiting
|
2.2%
1/46
|
1.7%
3/176
|
|
Gastrointestinal disorders
Diverticular Perforation
|
0.00%
0/46
|
1.1%
2/176
|
|
Gastrointestinal disorders
Abdominal Pain
|
2.2%
1/46
|
0.57%
1/176
|
|
Gastrointestinal disorders
Pancreatitis
|
2.2%
1/46
|
0.57%
1/176
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/46
|
0.57%
1/176
|
|
Gastrointestinal disorders
Gastrointestinal Haemorrhage
|
0.00%
0/46
|
0.57%
1/176
|
|
Gastrointestinal disorders
Gastrointestinal Perforation
|
0.00%
0/46
|
0.57%
1/176
|
|
Gastrointestinal disorders
Gastrointestinal Ulcer Haemorrhage
|
0.00%
0/46
|
0.57%
1/176
|
|
Gastrointestinal disorders
Oesophageal Stenosis
|
0.00%
0/46
|
0.57%
1/176
|
|
Gastrointestinal disorders
Rectal Haemorrhage
|
0.00%
0/46
|
0.57%
1/176
|
|
Gastrointestinal disorders
Haemorrhoidal Haemorrhage
|
2.2%
1/46
|
0.00%
0/176
|
|
General disorders
Disease Progression
|
0.00%
0/46
|
2.8%
5/176
|
|
General disorders
Asthenia
|
2.2%
1/46
|
0.57%
1/176
|
|
General disorders
Fatigue
|
2.2%
1/46
|
0.57%
1/176
|
|
General disorders
Chest Pain
|
0.00%
0/46
|
0.57%
1/176
|
|
General disorders
Death
|
0.00%
0/46
|
0.57%
1/176
|
|
General disorders
Gait Disturbance
|
0.00%
0/46
|
0.57%
1/176
|
|
General disorders
General Physical Health Deterioration
|
0.00%
0/46
|
0.57%
1/176
|
|
General disorders
Pyrexia
|
0.00%
0/46
|
0.57%
1/176
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/46
|
0.57%
1/176
|
|
Hepatobiliary disorders
Cholecystitis
|
2.2%
1/46
|
0.00%
0/176
|
|
Infections and infestations
Urinary Tract Infection
|
2.2%
1/46
|
1.1%
2/176
|
|
Infections and infestations
Pneumonia
|
0.00%
0/46
|
1.1%
2/176
|
|
Infections and infestations
Gastrointestinal Viral Infection
|
0.00%
0/46
|
0.57%
1/176
|
|
Infections and infestations
H1n1 Influenza
|
0.00%
0/46
|
0.57%
1/176
|
|
Infections and infestations
Infection
|
0.00%
0/46
|
0.57%
1/176
|
|
Infections and infestations
Meningitis
|
0.00%
0/46
|
0.57%
1/176
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/46
|
0.57%
1/176
|
|
Infections and infestations
Pneumocystis Jiroveci Pneumonia
|
0.00%
0/46
|
0.57%
1/176
|
|
Infections and infestations
Sepsis
|
0.00%
0/46
|
0.57%
1/176
|
|
Infections and infestations
Tooth Abscess
|
0.00%
0/46
|
0.57%
1/176
|
|
Infections and infestations
Wound Infection
|
0.00%
0/46
|
0.57%
1/176
|
|
Infections and infestations
Herpes Oesophagitis
|
2.2%
1/46
|
0.00%
0/176
|
|
Infections and infestations
Perirectal Abscess
|
2.2%
1/46
|
0.00%
0/176
|
|
Infections and infestations
Wound Infection Staphylococcal
|
2.2%
1/46
|
0.00%
0/176
|
|
Injury, poisoning and procedural complications
Wound Dehiscence
|
4.3%
2/46
|
1.7%
3/176
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/46
|
1.7%
3/176
|
|
Investigations
Alanine Aminotransferase Increased
|
2.2%
1/46
|
1.7%
3/176
|
|
Investigations
Aspartate Aminotransferase Increased
|
0.00%
0/46
|
1.7%
3/176
|
|
Investigations
Lipase Increased
|
2.2%
1/46
|
1.1%
2/176
|
|
Investigations
Troponin I Increased
|
4.3%
2/46
|
0.00%
0/176
|
|
Investigations
Amylase Increased
|
0.00%
0/46
|
0.57%
1/176
|
|
Investigations
Blood Bilirubin Increased
|
0.00%
0/46
|
0.57%
1/176
|
|
Investigations
Blood Creatinine Increased
|
0.00%
0/46
|
0.57%
1/176
|
|
Metabolism and nutrition disorders
Dehydration
|
2.2%
1/46
|
3.4%
6/176
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
0.00%
0/46
|
1.1%
2/176
|
|
Metabolism and nutrition disorders
Failure to Thrive
|
0.00%
0/46
|
0.57%
1/176
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/46
|
0.57%
1/176
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/46
|
0.57%
1/176
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
2.2%
1/46
|
1.7%
3/176
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
2.2%
1/46
|
0.57%
1/176
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/46
|
0.57%
1/176
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
0.00%
0/46
|
0.57%
1/176
|
|
Musculoskeletal and connective tissue disorders
Muscle Haemorrhage
|
2.2%
1/46
|
0.00%
0/176
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intracranial Tumor Haemorrhage
|
0.00%
0/46
|
1.1%
2/176
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glioblastoma
|
0.00%
0/46
|
0.57%
1/176
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor Haemorrhage
|
2.2%
1/46
|
0.00%
0/176
|
|
Nervous system disorders
Convulsion
|
13.0%
6/46
|
7.4%
13/176
|
|
Nervous system disorders
Hemiparesis
|
0.00%
0/46
|
4.5%
8/176
|
|
Nervous system disorders
Haemorrhage Intracranial
|
2.2%
1/46
|
1.7%
3/176
|
|
Nervous system disorders
Headache
|
0.00%
0/46
|
1.7%
3/176
|
|
Nervous system disorders
Ataxia
|
0.00%
0/46
|
1.1%
2/176
|
|
Nervous system disorders
Grand Mal Convulsion
|
0.00%
0/46
|
1.1%
2/176
|
|
Nervous system disorders
Lethargy
|
0.00%
0/46
|
1.1%
2/176
|
|
Nervous system disorders
Acquired Epileptic Aphasia
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Brain Stem Haemorrhage
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Cerebral Cyst
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Cerebral Haemorrhage
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Cerebral Infarction
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Coordination Abnormal
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Dizziness
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Hydrocephalus
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Intracranial Pressure Increased
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Ischaemic Cerebral Infarction
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Nervous System Disorder
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Pyramidal Tract Syndrome
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Somnolence
|
0.00%
0/46
|
0.57%
1/176
|
|
Nervous system disorders
Aphasia
|
2.2%
1/46
|
0.00%
0/176
|
|
Psychiatric disorders
Confusional State
|
6.5%
3/46
|
2.3%
4/176
|
|
Psychiatric disorders
Mental Status Changes
|
0.00%
0/46
|
2.3%
4/176
|
|
Psychiatric disorders
Psychotic Disorder
|
2.2%
1/46
|
0.00%
0/176
|
|
Renal and urinary disorders
Acute Prerenal Failure
|
0.00%
0/46
|
0.57%
1/176
|
|
Renal and urinary disorders
Urinary Incontinence
|
0.00%
0/46
|
0.57%
1/176
|
|
Renal and urinary disorders
Haematuria
|
2.2%
1/46
|
0.00%
0/176
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
4.3%
2/46
|
6.8%
12/176
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia Aspiration
|
2.2%
1/46
|
1.1%
2/176
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.2%
1/46
|
0.57%
1/176
|
|
Respiratory, thoracic and mediastinal disorders
Acute Interstitial Pneumonitis
|
0.00%
0/46
|
0.57%
1/176
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
0.00%
0/46
|
0.57%
1/176
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/46
|
0.57%
1/176
|
|
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome
|
0.00%
0/46
|
1.1%
2/176
|
|
Surgical and medical procedures
Craniotomy
|
0.00%
0/46
|
0.57%
1/176
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.00%
0/46
|
5.7%
10/176
|
|
Vascular disorders
Malignant Hypertension
|
0.00%
0/46
|
0.57%
1/176
|
|
Gastrointestinal disorders
Abdominal Distension
|
0.00%
0/46
|
0.57%
1/176
|
|
Infections and infestations
Clostridium Difficile Colitis
|
0.00%
0/46
|
0.57%
1/176
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
0.00%
0/46
|
0.57%
1/176
|
Other adverse events
| Measure |
Treatment Group A (175 mg)
n=46 participants at risk
Cabozantinib 175 mg (L-malate salt weight; 140 mg freebase equivalent) taken orally once per day (qd)
|
Treatment Group B + Group C (125 mg)
n=176 participants at risk
Cabozantinib 125 mg (L-malate salt weight; 100 mg freebase equivalent) taken orally once per day (qd)
|
|---|---|---|
|
General disorders
Fatigue
|
76.1%
35/46
|
75.0%
132/176
|
|
Gastrointestinal disorders
Diarrhoea
|
67.4%
31/46
|
55.1%
97/176
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
47.8%
22/46
|
37.5%
66/176
|
|
Gastrointestinal disorders
Nausea
|
37.0%
17/46
|
36.9%
65/176
|
|
Nervous system disorders
Headache
|
43.5%
20/46
|
33.5%
59/176
|
|
Gastrointestinal disorders
Constipation
|
47.8%
22/46
|
30.7%
54/176
|
|
Vascular disorders
Hypertension
|
39.1%
18/46
|
31.8%
56/176
|
|
Skin and subcutaneous tissue disorders
Palmar-Plantar Erythrodysaesthesia Syndrome
|
37.0%
17/46
|
31.8%
56/176
|
|
Investigations
Alanine Aminotransferase Increased
|
32.6%
15/46
|
30.7%
54/176
|
|
Investigations
Aspartate Aminotransferase Increased
|
34.8%
16/46
|
27.8%
49/176
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
39.1%
18/46
|
27.8%
49/176
|
|
Investigations
Blood Lactate Dehydrogenase Increased
|
23.9%
11/46
|
27.8%
49/176
|
|
Investigations
Weight Decreased
|
28.3%
13/46
|
26.1%
46/176
|
|
Nervous system disorders
Convulsion
|
19.6%
9/46
|
19.9%
35/176
|
|
Psychiatric disorders
Confusional State
|
17.4%
8/46
|
23.9%
42/176
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
17.4%
8/46
|
23.3%
41/176
|
|
Gastrointestinal disorders
Stomatitis
|
37.0%
17/46
|
17.6%
31/176
|
|
General disorders
Gait Disturbance
|
26.1%
12/46
|
19.3%
34/176
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.2%
1/46
|
23.3%
41/176
|
|
Gastrointestinal disorders
Vomiting
|
28.3%
13/46
|
16.5%
29/176
|
|
Psychiatric disorders
Insomnia
|
28.3%
13/46
|
15.9%
28/176
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
23.9%
11/46
|
16.5%
29/176
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
19.6%
9/46
|
17.6%
31/176
|
|
Gastrointestinal disorders
Abdominal Pain
|
26.1%
12/46
|
15.3%
27/176
|
|
Nervous system disorders
Memory Impairment
|
17.4%
8/46
|
17.6%
31/176
|
|
Renal and urinary disorders
Proteinuria
|
28.3%
13/46
|
14.8%
26/176
|
|
Skin and subcutaneous tissue disorders
Rash
|
19.6%
9/46
|
17.0%
30/176
|
|
Psychiatric disorders
Depression
|
10.9%
5/46
|
18.8%
33/176
|
|
Investigations
Lipase Increased
|
13.0%
6/46
|
17.0%
30/176
|
|
Psychiatric disorders
Anxiety
|
15.2%
7/46
|
16.5%
29/176
|
|
Skin and subcutaneous tissue disorders
Hair Colour Changes
|
21.7%
10/46
|
14.8%
26/176
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.2%
1/46
|
19.9%
35/176
|
|
Nervous system disorders
Cognitive Disorder
|
19.6%
9/46
|
15.3%
27/176
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
26.1%
12/46
|
13.1%
23/176
|
|
Gastrointestinal disorders
Oral Pain
|
10.9%
5/46
|
16.5%
29/176
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
30.4%
14/46
|
10.8%
19/176
|
|
Nervous system disorders
Dysgeusia
|
15.2%
7/46
|
14.8%
26/176
|
|
Gastrointestinal disorders
Dyspepsia
|
13.0%
6/46
|
15.3%
27/176
|
|
Nervous system disorders
Hemiparesis
|
6.5%
3/46
|
15.3%
27/176
|
|
General disorders
Oedema Peripheral
|
15.2%
7/46
|
14.2%
25/176
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
15.2%
7/46
|
13.1%
23/176
|
|
Nervous system disorders
Speech Disorder
|
10.9%
5/46
|
14.2%
25/176
|
|
Nervous system disorders
Dizziness
|
26.1%
12/46
|
9.1%
16/176
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
17.4%
8/46
|
11.9%
21/176
|
|
Infections and infestations
Urinary Tract Infection
|
19.6%
9/46
|
10.2%
18/176
|
|
Blood and lymphatic system disorders
Lymphopenia
|
21.7%
10/46
|
10.8%
19/176
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
15.2%
7/46
|
11.4%
20/176
|
|
Blood and lymphatic system disorders
Neutropenia
|
13.0%
6/46
|
11.9%
21/176
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
10.9%
5/46
|
11.9%
21/176
|
|
Nervous system disorders
Ataxia
|
6.5%
3/46
|
10.8%
19/176
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
17.4%
8/46
|
8.5%
15/176
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
10.9%
5/46
|
9.7%
17/176
|
|
General disorders
Mucosal Inflammation
|
6.5%
3/46
|
11.4%
20/176
|
|
Cardiac disorders
Sinus Bradycardia
|
8.7%
4/46
|
10.8%
19/176
|
|
Psychiatric disorders
Agitation
|
8.7%
4/46
|
10.2%
18/176
|
|
Nervous system disorders
Aphasia
|
13.0%
6/46
|
8.0%
14/176
|
|
General disorders
Asthenia
|
4.3%
2/46
|
9.7%
17/176
|
|
Vascular disorders
Deep Vein Thrombosis
|
4.3%
2/46
|
5.1%
9/176
|
|
Nervous system disorders
Peripheral Sensory Neuropathy
|
6.5%
3/46
|
9.7%
17/176
|
|
Investigations
Blood Bilirubin Increased
|
15.2%
7/46
|
6.2%
11/176
|
|
Gastrointestinal disorders
Dysphagia
|
6.5%
3/46
|
9.1%
16/176
|
|
Nervous system disorders
Nervous System Disorder
|
13.0%
6/46
|
6.8%
12/176
|
|
Metabolism and nutrition disorders
Dehydration
|
8.7%
4/46
|
5.1%
9/176
|
|
Nervous system disorders
Somnolence
|
10.9%
5/46
|
6.8%
12/176
|
|
Renal and urinary disorders
Urinary Incontinence
|
6.5%
3/46
|
8.5%
15/176
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.7%
4/46
|
7.4%
13/176
|
|
Gastrointestinal disorders
Dry Mouth
|
8.7%
4/46
|
7.4%
13/176
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
19.6%
9/46
|
4.5%
8/176
|
|
Endocrine disorders
Hypothyroidism
|
13.0%
6/46
|
6.2%
11/176
|
|
Eye disorders
Vision Blurred
|
15.2%
7/46
|
5.7%
10/176
|
|
Blood and lymphatic system disorders
Anaemia
|
6.5%
3/46
|
7.4%
13/176
|
|
Gastrointestinal disorders
Flatulence
|
6.5%
3/46
|
7.4%
13/176
|
|
Gastrointestinal disorders
Gastrooesophageal Reflux Disease
|
8.7%
4/46
|
6.2%
11/176
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
8.7%
4/46
|
6.2%
11/176
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis Allergic
|
13.0%
6/46
|
5.1%
9/176
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
8.7%
4/46
|
5.7%
10/176
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
6.5%
3/46
|
6.2%
11/176
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
4.3%
2/46
|
6.8%
12/176
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
8.7%
4/46
|
5.7%
10/176
|
|
Investigations
Amylase Increased
|
4.3%
2/46
|
6.2%
11/176
|
|
Injury, poisoning and procedural complications
Contusion
|
4.3%
2/46
|
6.2%
11/176
|
|
Nervous system disorders
Dysarthria
|
4.3%
2/46
|
6.2%
11/176
|
|
Gastrointestinal disorders
Faecal Incontinence
|
4.3%
2/46
|
6.2%
11/176
|
|
Gastrointestinal disorders
Haemorrhoids
|
15.2%
7/46
|
3.4%
6/176
|
|
Infections and infestations
Oral Candidiasis
|
4.3%
2/46
|
6.2%
11/176
|
|
Investigations
Blood Alkaline Phosphatase Increased
|
10.9%
5/46
|
4.0%
7/176
|
|
Nervous system disorders
Amnesia
|
8.7%
4/46
|
4.0%
7/176
|
|
Nervous system disorders
Balance Disorder
|
0.00%
0/46
|
6.2%
11/176
|
|
Gastrointestinal disorders
Glossodynia
|
8.7%
4/46
|
4.0%
7/176
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
2.2%
1/46
|
5.1%
9/176
|
|
Nervous system disorders
Paraesthesia
|
4.3%
2/46
|
5.1%
9/176
|
|
Nervous system disorders
Peripheral Motor Neuropathy
|
6.5%
3/46
|
4.5%
8/176
|
|
General disorders
Pyrexia
|
6.5%
3/46
|
4.0%
7/176
|
|
General disorders
Chills
|
10.9%
5/46
|
2.8%
5/176
|
|
Nervous system disorders
Hypoaesthesia
|
6.5%
3/46
|
3.4%
6/176
|
|
Investigations
Platelet Count Decreased
|
13.0%
6/46
|
2.3%
4/176
|
|
Infections and infestations
Sinusitis
|
6.5%
3/46
|
4.0%
7/176
|
|
Skin and subcutaneous tissue disorders
Skin Hypopigmentation
|
2.2%
1/46
|
5.1%
9/176
|
|
Investigations
Blood Phosphorus Decreased
|
8.7%
4/46
|
2.8%
5/176
|
|
Investigations
Haemoglobin Decreased
|
13.0%
6/46
|
1.7%
3/176
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
6.5%
3/46
|
3.4%
6/176
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
6.5%
3/46
|
2.8%
5/176
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
8.7%
4/46
|
2.8%
5/176
|
|
Skin and subcutaneous tissue disorders
Skin Discolouration
|
15.2%
7/46
|
1.1%
2/176
|
|
Investigations
White Blood Cell Count Decreased
|
10.9%
5/46
|
2.3%
4/176
|
|
Nervous system disorders
Disturbance in Attention
|
8.7%
4/46
|
2.3%
4/176
|
|
Investigations
Blood Calcium Decreased
|
10.9%
5/46
|
1.1%
2/176
|
|
Investigations
Neutrophil Count Decreased
|
6.5%
3/46
|
2.3%
4/176
|
|
General disorders
Non-Cardiac Chest Pain
|
8.7%
4/46
|
1.7%
3/176
|
|
Eye disorders
Dry Eye
|
8.7%
4/46
|
1.1%
2/176
|
|
Gastrointestinal disorders
Proctalgia
|
6.5%
3/46
|
1.7%
3/176
|
|
Renal and urinary disorders
Urinary Retention
|
6.5%
3/46
|
1.1%
2/176
|
|
Investigations
Blood Albumin Decreased
|
6.5%
3/46
|
0.57%
1/176
|
|
General disorders
Oedema
|
6.5%
3/46
|
0.00%
0/176
|
|
Nervous system disorders
Visual Field Defect
|
6.5%
3/46
|
6.8%
12/176
|
|
Skin and subcutaneous tissue disorders
Dermatitis Acneiform
|
6.5%
3/46
|
4.0%
7/176
|
|
Investigations
Electrocardiogram T Wave Abnormal
|
0.00%
0/46
|
5.7%
10/176
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Dryness
|
6.5%
3/46
|
0.57%
1/176
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place