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Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM)

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ClinicalTrials.gov Identifier: NCT00704730
Recruitment Status : Unknown
Verified August 2015 by Exelixis.
Recruitment status was:  Active, not recruiting
First Posted : June 25, 2008
Results First Posted : September 9, 2014
Last Update Posted : August 27, 2015
Sponsor:
Information provided by (Responsible Party):
Exelixis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Thyroid Cancer
Interventions Drug: XL184
Drug: Placebo
Enrollment 330
Recruitment Details First patient enrolled 10 September 2008, last patient enrolled 27 February 2011. Data cut off date 15 June 2011.
Pre-assignment Details  
Arm/Group Title XL184 (Cabozantinib) Placebo
Hide Arm/Group Description XL184 175 mg L-malate salt weight; 138 mg freebase equivalent weight, oral capsules once daily oral capsules once daily
Period Title: Overall Study
Started 219 [1] 111 [1]
Completed 98 [2] 15 [2]
Not Completed 121 96
Reason Not Completed
Adverse Event             35             9
Death             11             5
Physician Decision             2             0
Did not receive drug             5             2
Disease progression per PI             58             67
data unavailable             1             0
Withdrawal by Subject             9             13
[1]
Randomized
[2]
Continuing study treatment at the time of data cut-off.
Arm/Group Title XL184 (Cabozantinib) Placebo Total
Hide Arm/Group Description XL184 175 mg L-malate salt weight; 138 mg freebase equivalent weight, oral capsules once daily oral capsules once daily Total of all reporting groups
Overall Number of Baseline Participants 219 111 330
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 219 participants 111 participants 330 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
172
  78.5%
86
  77.5%
258
  78.2%
>=65 years
47
  21.5%
25
  22.5%
72
  21.8%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 219 participants 111 participants 330 participants
54.4  (13.33) 53.8  (13.39) 54.2  (13.33)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 219 participants 111 participants 330 participants
Female
68
  31.1%
41
  36.9%
109
  33.0%
Male
151
  68.9%
70
  63.1%
221
  67.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 219 participants 111 participants 330 participants
Austria 8 1 9
Belgium 7 5 12
Brazil 4 3 7
Canada 6 2 8
Chile 0 1 1
Denmark 1 0 1
France 25 5 30
Germany 15 10 25
Greece 1 2 3
Portugal 0 1 1
India 5 1 6
Israel 5 4 9
Italy 28 14 42
Korea, Republic of 3 4 7
Netherlands 5 3 8
Peru 1 0 1
Poland 12 3 15
Russian Federation 8 5 13
Spain 5 3 8
Switzerland 1 0 1
Sweden 6 4 10
United Kingdom 10 9 19
United States 63 31 94
1.Primary Outcome
Title Progression-Free Survival (PFS)
Hide Description The duration of Progression-Free Survival (PFS) using progression events as determined by Independent Review Committee (IRC) per mRECIST, or death due to any cause. The analysis was conducted after at least 315 subjects were randomized and at least 138 events were observed.
Time Frame Treatment period consisted of 4-week cycles with radiologic tumor assessment every 12 weeks from date of randomization until date of first documented PD or date of death from any cause, whichever came first, assessed up to 34 months.
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Hide Analysis Population Description
Intent to Treat (ITT) 330 subjects were randomized and were included in the analysis. A Kaplan-Meyer analysis was performed to estimate the median.
Arm/Group Title XL184 (Cabozantinib) Placebo
Hide Arm/Group Description:
XL184 175 mg L-malate salt weight; 138 mg freebase equivalent weight, oral capsules once daily.
Oral capsules once daily
Overall Number of Participants Analyzed 219 111
Median (95% Confidence Interval)
Unit of Measure: months
11.2
(9.3 to 13.7)
4.0
(3.0 to 5.4)
2.Secondary Outcome
Title Overall Survival (OS) With XL184 Compared With Placebo
Hide Description Duration of Overall Survival (OS) from the time of randomization to death due to any cause. A Kaplan-Meier analysis was performed to estimate the median.
Time Frame The pre-specified interim analysis of Overall Survival (OS) was assessed at 44% of required events. Includes data up to 15June2011. As of this date, the number of deaths required to conduct the primary analysis had not been reached.
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Hide Analysis Population Description
Intent to treat (ITT) randomized to either XL184 or placebo
Arm/Group Title XL184 (Cabozantinib) Placebo
Hide Arm/Group Description:
XL184 175 mg L-malate salt weight; 138 mg freebase equivalent weight, oral capsules once daily
Oral capsules once daily
Overall Number of Participants Analyzed 219 111
Median (95% Confidence Interval)
Unit of Measure: months
21.1
(16.59 to 28.52)
NA [1] 
(17.41 to NA)
[1]
Median duration OS could not be estimated for placebo at data cut-off June 15, 2011 due to insufficient number of participants with events. At time of analysis of PFS, number of deaths required to conduct primary analysis of OS was not reached.
3.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description The proportion of subjects with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) as determined by the Independent Review Committee (IRC.) Per Response Evaluation Criteria in Solid Tumor Criteria (mRECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR) disappearance of all target lesions; Partial Response (PR) ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) ≥ 20% increase in the sum of the longest diameter of target lesions. Overall Response Rate: ORR=CR +PR
Time Frame Assessed at the same time as primary analysis of Progression Free Survival (PFS) data. Assessed at baseline and every 12 weeks until Progressive Disease (PD) up to 34 months.
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Hide Analysis Population Description
The primary analysis Objective Response Rate (ORR) was performed among subset of Intent To Treat (ITT) subjects with measurable disease at baseline (N = 208 cabozantinib, N = 104 placebo) based upon response determined by Independent Radiology Committee (IRC.) Subjects without post-baseline adequate tumor assessments - counted as nonresponders.
Arm/Group Title XL184 (Cabozantinib) Placebo
Hide Arm/Group Description:
XL184 175 mg L-malate salt weight; 138 mg freebase equivalent weight, oral capsules once daily
Oral capsules once daily
Overall Number of Participants Analyzed 208 104
Measure Type: Number
Unit of Measure: % of participants
28 0
4.Secondary Outcome
Title Duration of Objective Response (OR): Independent Radiology Committee (IRC) Determined
Hide Description For those subjects with Independent Radiology Committee (IRC) determined Objective Response Rate (ORR), the amount of time from documentation of Objective Response (OR) until Progressive Disease (PD) by mRECIST or death due to any cause.
Time Frame From time of first documentation of Objective Response (OR), confirmed at a later visit ≥28 days later as Progressive Disease (PD) as defined by mRECIST or death due to any cause, assessed up to 34 months.
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Hide Analysis Population Description
The primary analysis of Objective Response Rate (ORR) was performed among the subset of Intent To Treat (ITT) subjects with measurable disease at baseline and was based upon response as determined by the Independent Review Committee (IRC.) Subjects who did not have post-baseline adequate tumor assessments were counted as nonresponders.
Arm/Group Title XL184 (Cabozantinib) Placebo
Hide Arm/Group Description:
XL184 175 mg L-malate salt weight; 138 mg freebase equivalent weight, oral capsules once daily
Oral capsules once daily
Overall Number of Participants Analyzed 58 0
Median (95% Confidence Interval)
Unit of Measure: months
14.6
(11.1 to 17.5)
5.Secondary Outcome
Title Biochemical Response Calcitonin (CTN) %
Hide Description For each on-treatment tumor marker assessment from each subject, the biochemical response of CTN was determined based on percent increase or decrease from baseline. Best biochemical response over course of treatment was determined from evaluation of subject’s time point response data. Biochemical response criteria: Complete Response (CR) - decrease in tumor marker into normal range from baseline value; Partial Response (PR) - decrease of >50% from baseline value when baseline value is above normal range; Stable Disease (SD) - no more than a 50% increase and no more than a 50% decrease from baseline value above normal range; Progressive Disease (PD) - increase of >50% from baseline value when baseline value is above normal range / or increase from low or normal range at baseline to above normal range; Not Evaluable (NE) - missing baseline value / or baseline value is not elevated and response is not PD / or response can not be determined due to change in assay format.
Time Frame Serum tumor markers CTN evaluated from blood samples collected at screening and every 12 weeks (±5 days from randomization) until date of first documented progression or date of death from any cause, whichever came first, assessed for up to 34 months.
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Hide Analysis Population Description
Population was intent to treat (ITT), randomized to either XL184 or placebo. For the CTN measure the analysis population differs from the ITT population of 219 XL184 and 111 Placebo. Three subjects did not provide samples for CTN. The biomarker analysis was based on available samples, not on ITT.
Arm/Group Title XL184 (Cabozantinib) Placebo
Hide Arm/Group Description:
XL184 175 mg L-malate salt weight; 138 mg freebase equivalent weight, oral capsules once daily
Oral capsules once daily
Overall Number of Participants Analyzed 217 110
Measure Type: Number
Unit of Measure: % participants
22.6 0.9
6.Secondary Outcome
Title Biochemical Response Carcinoembryonic Antigen (CEA) %
Hide Description For each on-treatment tumor marker assessment from each subject, the biochemical response of CEA was determined based on percent increase or decrease from baseline. Best biochemical response over the course of treatment was determined from evaluation of each subject’s time point response data. Biochemical response: Complete Response (CR)- Decrease in tumor marker into normal range from baseline value; Partial Response (PR)- Decrease of >50% from baseline value when baseline value is above normal range; Stable Disease (SD)- No more than a 50% increase and no more than a 50% decrease from baseline value above normal range; Progressive Disease (PD)- Increase of >50% from baseline value when baseline value is above normal range / or increase from low or normal range at baseline to above normal range; Not Evaluable (NE)- Missing baseline value / or baseline value is not elevated and response is not Progressive Disease (PD) / or response can not be determined due to change in assay format.
Time Frame Serum tumor markers CEA evaluated from blood samples collected at screening and every 12 weeks (± 5 days from randomization) until date of first documented progression or date of death from any cause, whichever came first, assessed for up to 34 months.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
For the CEA measure the analysis population differs from the Intent To Treat (ITT) population of 219 XL184 and 111 Placebo. One subject did not provide samples for CEA. The biomarker analysis was based on available samples, not on ITT.
Arm/Group Title XL184 (Cabozantinib) Placebo
Hide Arm/Group Description:
XL184 175 mg L-malate salt weight; 138 mg freebase equivalent weight, oral capsules once daily
Oral capsules once daily
Overall Number of Participants Analyzed 218 111
Measure Type: Number
Unit of Measure: % of participants
21.6 0.9
Time Frame 10 September 2008 - 15 June 2011
Adverse Event Reporting Description The safety data includes subjects who were randomized and treated. Of 330 subjects, 219 were randomized to receive XL184, 111 placebo. Seven subjects were randomized and not treated; there were 214 subjects treated with XL184 and 109 subjects who received placebo.
 
Arm/Group Title XL184 (Cabozantinib) Placebo
Hide Arm/Group Description XL184 175 mg L-malate salt weight; 138 mg freebase equivalent weight, oral capsules once daily oral capsules once daily
All-Cause Mortality
XL184 (Cabozantinib) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
XL184 (Cabozantinib) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   90/214 (42.06%)      25/109 (22.94%)    
Blood and lymphatic system disorders     
Haemolytic uraemic syndrome  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Pancytopenia  1  1/214 (0.47%)  1 1/109 (0.92%)  1
Thrombocytopenia  1  3/214 (1.40%)  3 0/109 (0.00%)  0
Cardiac disorders     
Atrial fibrillation  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Atrial flutter  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Cardiac arrest  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Cardiopulmonary failure  1  1/214 (0.47%)  1 1/109 (0.92%)  1
Left ventricular dysfunction  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Supraventricular tachycardia  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Ear and labyrinth disorders     
Hypoacusis  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Endocrine disorders     
Ectopic acth syndrome  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Gastrointestinal disorders     
Abdominal pain  1  3/214 (1.40%)  3 0/109 (0.00%)  0
Anal fissure  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Anal fistula  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Aphthous stomatitis  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Ascites  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Diarrhoea  1  3/214 (1.40%)  3 1/109 (0.92%)  1
Duodenal ulcer haemorrhage  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Dysphagia  1  5/214 (2.34%)  5 2/109 (1.83%)  2
Enterocolitis  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Gastric perforation  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Gastrointestinal disorder  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Gingival bleeding  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Glossodynia  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Haemorrhoidal haemorrhage  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Haemorrhoids  1  2/214 (0.93%)  2 0/109 (0.00%)  0
Intestinal haemorrhage  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Large intestine perforation  1  2/214 (0.93%)  2 0/109 (0.00%)  0
Nausea  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Oesophageal fistula  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Oesophageal ulcer  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Pancreatitis  1  3/214 (1.40%)  3 0/109 (0.00%)  0
Pancreatitis chronic  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Peritonitis  1  2/214 (0.93%)  2 0/109 (0.00%)  0
Pneumoperitonem  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Proctalgia  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Vomiting  1  4/214 (1.87%)  4 1/109 (0.92%)  1
General disorders     
Asthenia  1  2/214 (0.93%)  2 2/109 (1.83%)  2
Chest pain  1  1/214 (0.47%)  1 1/109 (0.92%)  1
Death  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Fatigue  1  4/214 (1.87%)  4 1/109 (0.92%)  1
General physical health deterioration  1  1/214 (0.47%)  1 2/109 (1.83%)  2
Injection site haematoma  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Mucosal inflammation  1  6/214 (2.80%)  6 0/109 (0.00%)  0
Multi-organ failure  1  3/214 (1.40%)  3 0/109 (0.00%)  0
Non-cardiac chest pain  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Oedema peripheral  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Performance status decreased  1  2/214 (0.93%)  2 1/109 (0.92%)  1
Pyrexia  1  2/214 (0.93%)  2 0/109 (0.00%)  0
Sudden death  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Hepatobiliary disorders     
Hepatic cirrhosis  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Hepatic failure  1  1/214 (0.47%)  1 1/109 (0.92%)  1
Hepatitis toxic  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Immune system disorders     
Hypersensitivity  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Infections and infestations     
Anal abscess  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Appendicitis perforated  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Aspergilloma  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Bronchitis  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Bronchopneumonia  1  2/214 (0.93%)  2 0/109 (0.00%)  0
Clostridial infection  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Device related infection  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Fungal oesophagitis  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Gastrointestinal infection  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Infectious mononucleosis  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Lower respiratory tract infection  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Lung abscess  1  3/214 (1.40%)  3 0/109 (0.00%)  0
Peridiverticular abscess  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Pneumonia  1  7/214 (3.27%)  7 3/109 (2.75%)  3
Pneumonia bacterial  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Salmonellosis  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Sepsis  1  3/214 (1.40%)  3 0/109 (0.00%)  0
Septic shock  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Tracheitis  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Upper respiratory tract infection  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Urinary tract infection  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Wound infection  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Respiratory tract infection  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Injury, poisoning and procedural complications     
Lower limb fracture  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Post procedural haemorrhage  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Spinal compression fracture  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Tracheal haemorrhage  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Investigations     
Blood amylase increased  1  1/214 (0.47%)  1 1/109 (0.92%)  1
Blood lactate dehydrogenase increased  1  1/214 (0.47%)  1 0/109 (0.00%)  0
C-reactive protein increased  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Electrocardiogram QT prolonged  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Electrocardiogram ST segment depression  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Eosinophil count increased  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Haemoglobin decreased  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Lipase increased  1  3/214 (1.40%)  3 1/109 (0.92%)  1
Liver function test abnormal  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Transaminases increased  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite  1  2/214 (0.93%)  2 0/109 (0.00%)  0
Dehydration  1  5/214 (2.34%)  5 1/109 (0.92%)  1
Hypercalcaemia  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Hypocalcaemia  1  6/214 (2.80%)  6 0/109 (0.00%)  0
Hypokalaemia  1  3/214 (1.40%)  3 0/109 (0.00%)  0
Hyponatraemia  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Back pain  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Bone pain  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Muscle spasms  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Neck pain  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Osteonecrosis of jaw  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Bladder transitional cell carcinoma  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Metastases to oesophagus  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Metastases to trachea  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Metastatic pain  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Neoplasm progression  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Tumor pain  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Nervous system disorders     
Cerebral infarction  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Cervicobrachial syndrome  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Convulsion  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Hepatic encephalopathy  1  2/214 (0.93%)  2 0/109 (0.00%)  0
Hypoxic-ischaemic encephalopathy  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Loss of consciousness  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Posterior reversible encephalopathy syndrome  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Syncope  1  2/214 (0.93%)  2 0/109 (0.00%)  0
Transient ischaemic attack  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Vocal cord paralysis  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Psychiatric disorders     
Agitation  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Confusional state  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Delirium  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Suicide attempt  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Renal and urinary disorders     
Acute prerenal failure  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Nephrotic syndrome  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Proteinuria  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Renal failure  1  2/214 (0.93%)  2 0/109 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Acquired tracheo-oesophageal fistula  1  3/214 (1.40%)  3 0/109 (0.00%)  0
Acute respiratory distress syndrome  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Acute respiratory failure  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Aspiration  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Atelectasis  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Bronchial haemorrhage  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Dyspnoea  1  2/214 (0.93%)  2 6/109 (5.50%)  6
Epistaxis  1  2/214 (0.93%)  2 1/109 (0.92%)  1
Haemoptysis  1  2/214 (0.93%)  2 0/109 (0.00%)  0
Laryngeal oedema  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Lung infiltration  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Nasal septum perforation  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Obstructive airways disorder  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Pharyngeal oedema  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Pleuritic pain  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Pneumomediastinum  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Pneumonia aspiration  1  4/214 (1.87%)  4 1/109 (0.92%)  1
Pneumothorax  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Pulmonary embolism  1  5/214 (2.34%)  5 0/109 (0.00%)  0
Pulmonary haemorrhage  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Pulmonary necrosis  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Rales  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Respiratory failure  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Respiratory tract haemorrhage  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Tracheal fistula  1  2/214 (0.93%)  2 0/109 (0.00%)  0
Skin and subcutaneous tissue disorders     
Palmar-plantar erythrodysaesthesia syndrome  1  3/214 (1.40%)  3 0/109 (0.00%)  0
Rash  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Vascular disorders     
Arterial thrombosis limb  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Deep vein thrombosis  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Haemorrhage  1  1/214 (0.47%)  1 0/109 (0.00%)  0
Hypertension  1  5/214 (2.34%)  5 0/109 (0.00%)  0
Hypotension  1  3/214 (1.40%)  3 0/109 (0.00%)  0
Shock  1  0/214 (0.00%)  0 1/109 (0.92%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (14.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
XL184 (Cabozantinib) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   213/214 (99.53%)      102/109 (93.58%)    
Blood and lymphatic system disorders     
Anaemia  1  14/214 (6.54%)  14 10/109 (9.17%)  10
Leukopenia  1  11/214 (5.14%)  11 2/109 (1.83%)  2
Endocrine disorders     
Hypothyroidism  1  20/214 (9.35%)  20 1/109 (0.92%)  1
Gastrointestinal disorders     
Abdominal pain  1  34/214 (15.89%)  34 7/109 (6.42%)  7
Abdominal pain upper  1  16/214 (7.48%)  16 6/109 (5.50%)  6
Constipation  1  57/214 (26.64%)  57 6/109 (5.50%)  6
Diarrhoea  1  135/214 (63.08%)  135 36/109 (33.03%)  36
Dry mouth  1  28/214 (13.08%)  28 9/109 (8.26%)  9
Dyspepsia  1  24/214 (11.21%)  24 0/109 (0.00%)  0
Dysphagia  1  25/214 (11.68%)  25 7/109 (6.42%)  7
Flatulence  1  15/214 (7.01%)  15 4/109 (3.67%)  4
Glossodynia  1  21/214 (9.81%)  21 0/109 (0.00%)  0
Haemorrhoids  1  17/214 (7.94%)  17 3/109 (2.75%)  3
Nausea  1  92/214 (42.99%)  92 23/109 (21.10%)  23
Oral pain  1  29/214 (13.55%)  29 1/109 (0.92%)  1
Stomatitis  1  62/214 (28.97%)  62 3/109 (2.75%)  3
Vomiting  1  51/214 (23.83%)  51 2/109 (1.83%)  2
General disorders     
Asthenia  1  43/214 (20.09%)  43 14/109 (12.84%)  14
Fatigue  1  86/214 (40.19%)  86 31/109 (28.44%)  31
Mucosal inflamation  1  46/214 (21.50%)  46 4/109 (3.67%)  4
Oedema peripheral  1  20/214 (9.35%)  20 13/109 (11.93%)  13
Pain  1  12/214 (5.61%)  12 4/109 (3.67%)  4
Pyrexia  1  19/214 (8.88%)  19 7/109 (6.42%)  7
Infections and infestations     
Nasopharyngitis  1  10/214 (4.67%)  10 8/109 (7.34%)  8
Upper respiratory tract infection  1  17/214 (7.94%)  17 4/109 (3.67%)  4
Urinary tract infection  1  16/214 (7.48%)  16 3/109 (2.75%)  3
Investigations     
Alanine aminotransferase increased  1  46/214 (21.50%)  46 6/109 (5.50%)  6
Aspartate aminotransferase increased  1  46/214 (21.50%)  46 6/109 (5.50%)  6
Blood alkaline phosphatase increased  1  17/214 (7.94%)  17 3/109 (2.75%)  3
Blood amylase increased  1  14/214 (6.54%)  14 11/109 (10.09%)  11
Blood lactate dehydrogenase increased  1  39/214 (18.22%)  39 3/109 (2.75%)  3
Blood thyroid stimulating hormone increased  1  28/214 (13.08%)  28 3/109 (2.75%)  3
Lipase increased  1  23/214 (10.75%)  23 13/109 (11.93%)  13
Weight decreased  1  102/214 (47.66%)  102 11/109 (10.09%)  11
Metabolism and nutrition disorders     
Decreased appetite  1  98/214 (45.79%)  98 17/109 (15.60%)  17
Dehydration  1  12/214 (5.61%)  12 1/109 (0.92%)  1
Hypocalcaemia  1  43/214 (20.09%)  43 5/109 (4.59%)  5
Hypokalaemia  1  22/214 (10.28%)  22 4/109 (3.67%)  4
Musculoskeletal and connective tissue disorders     
Arthralgia  1  28/214 (13.08%)  28 8/109 (7.34%)  8
Back pain  1  32/214 (14.95%)  32 12/109 (11.01%)  12
Bone pain  1  11/214 (5.14%)  11 5/109 (4.59%)  5
Joint swelling  1  2/214 (0.93%)  2 6/109 (5.50%)  6
Muscle spasms  1  26/214 (12.15%)  26 5/109 (4.59%)  5
Musculoskeletal chest pain  1  19/214 (8.88%)  19 4/109 (3.67%)  4
Musculoskeletal pain  1  12/214 (5.61%)  12 6/109 (5.50%)  6
Myalgia  1  13/214 (6.07%)  13 4/109 (3.67%)  4
Neck pain  1  15/214 (7.01%)  15 5/109 (4.59%)  5
Pain in extremity  1  33/214 (15.42%)  33 12/109 (11.01%)  12
Nervous system disorders     
Dizziness  1  29/214 (13.55%)  29 8/109 (7.34%)  8
Dysgeusia  1  73/214 (34.11%)  73 6/109 (5.50%)  6
Headache  1  39/214 (18.22%)  39 9/109 (8.26%)  9
Neuropathy peripheral  1  11/214 (5.14%)  11 0/109 (0.00%)  0
Paraesthesia  1  16/214 (7.48%)  16 2/109 (1.83%)  2
Peripheral sensory neuropathy  1  14/214 (6.54%)  14 0/109 (0.00%)  0
Psychiatric disorders     
Anxiety  1  19/214 (8.88%)  19 2/109 (1.83%)  2
Depression  1  14/214 (6.54%)  14 3/109 (2.75%)  3
Insomnia  1  23/214 (10.75%)  23 7/109 (6.42%)  7
Respiratory, thoracic and mediastinal disorders     
Cough  1  26/214 (12.15%)  26 14/109 (12.84%)  14
Dysphonia  1  43/214 (20.09%)  43 10/109 (9.17%)  10
Dyspnoea  1  27/214 (12.62%)  27 18/109 (16.51%)  18
Epistaxis  1  19/214 (8.88%)  19 12/109 (11.01%)  12
Oropharyngeal pain  1  38/214 (17.76%)  38 5/109 (4.59%)  5
Skin and subcutaneous tissue disorders     
Alopecia  1  35/214 (16.36%)  35 2/109 (1.83%)  2
Dermatitis acneiform  1  14/214 (6.54%)  14 2/109 (1.83%)  2
Dry skin  1  41/214 (19.16%)  41 3/109 (2.75%)  3
Erythema  1  23/214 (10.75%)  23 2/109 (1.83%)  2
Hair colour changes  1  72/214 (33.64%)  72 1/109 (0.92%)  1
Hyperhidrosis  1  4/214 (1.87%)  4 6/109 (5.50%)  6
Hyperkeratosis  1  16/214 (7.48%)  16 0/109 (0.00%)  0
Palmar-plantar erythrodysaesthesia syndrome  1  105/214 (49.07%)  105 2/109 (1.83%)  2
Pruritus  1  13/214 (6.07%)  13 7/109 (6.42%)  7
Rash  1  41/214 (19.16%)  41 11/109 (10.09%)  11
Vascular disorders     
Hypertension  1  62/214 (28.97%)  62 4/109 (3.67%)  4
Hypotension  1  11/214 (5.14%)  11 0/109 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (14.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
PIs may publish trial results generated at his/ her site with sponsor’s prior written consent and only after results of the trial from all participating sites have been released in a multi-center publication coordinated by the sponsor.
Results Point of Contact
Name/Title: Yifah Yaron, MD Senior Director, Clinical Research, Clinical Development
Organization: Exelixis, Inc
Phone: 650-837-7678
Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT00704730     History of Changes
Other Study ID Numbers: XL184-301
First Submitted: June 23, 2008
First Posted: June 25, 2008
Results First Submitted: April 8, 2014
Results First Posted: September 9, 2014
Last Update Posted: August 27, 2015