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A Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma (METEOR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01865747
Recruitment Status : Active, not recruiting
First Posted : May 31, 2013
Results First Posted : July 18, 2017
Last Update Posted : May 22, 2018
Sponsor:
Information provided by (Responsible Party):
Exelixis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Renal Cell Carcinoma
Interventions Drug: Cabozantinib tablets
Drug: Everolimus (Afinitor) tablets
Enrollment 658
Recruitment Details First patient enrolled: 08 August 2013, Data cut off date: 22 May 2015
Pre-assignment Details  
Arm/Group Title Cabozantinib (XL184) Everolimus (Afinitor)
Hide Arm/Group Description

Cabozantinib (XL184) 60 mg tablet once daily.

Cabozantinib tablets

Everolimus (Afinitor) 10 mg tablet once daily.

Everolimus (Afinitor) tablets

Period Title: Overall Study (ITT)
Started [1] 330 328
Completed [2] 132 [3] 73 [4]
Not Completed 198 255
Reason Not Completed
Adverse Event             32             31
Clinical Deterioration             29             50
Lack of Efficacy             3             0
Protocol Violation             1             1
Physician Decision             5             2
Withdrawal by Subject             6             11
Sponsor Decision             0             1
Progressive Disease             122             158
Reason Not Provided             0             1
[1]
Randomized
[2]
Continuing study treatment at the time of data cut-off
[3]
One subject randomized to everolimus arm received cabozantinib discontd due to clin. deterioration
[4]
Five subjects were randomized but not treated
Period Title: Primary Intent to Treat (PITT)
Started [1] 187 188 [2]
Completed [3] 56 36
Not Completed 131 152
Reason Not Completed
Adverse Event             21             20
Clinical Deterioration             18             29
Lack of Efficacy             2             0
Protocol Violation             1             1
Physician Decision             4             2
Withdrawal by Subject             3             7
Progressive Disease             82             92
Other             0             1
[1]
PITT population consisted of the first 375 subjects randomized to received study treatment.
[2]
Three subjects in the everolimus arm were randomized but not treated.
[3]
Continuing study treatment at the time of data cut-off
Arm/Group Title Cabozantinib (XL184) Everolimus (Afinitor) Total
Hide Arm/Group Description

Cabozantinib (XL184) 60 mg tablet once daily.

Cabozantinib tablets

Everolimus (Afinitor) 10 mg tablet once daily.

Everolimus (Afinitor) tablets

Total of all reporting groups
Overall Number of Baseline Participants 330 328 658
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 330 participants 328 participants 658 participants
<65 196 198 394
65 to <75 107 94 201
75 to <85 26 36 62
=>85 1 0 1
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 330 participants 328 participants 658 participants
Male 253 241 494
Female 77 86 163
Missing 0 1 1
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Ethnicity Number Analyzed 330 participants 328 participants 658 participants
Hispanic or Latino
19
   5.8%
18
   5.5%
37
   5.6%
Not Hispanic or Latino
278
  84.2%
273
  83.2%
551
  83.7%
Unknown or Not Reported
33
  10.0%
37
  11.3%
70
  10.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 330 participants 328 participants 658 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
21
   6.4%
26
   7.9%
47
   7.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
   1.8%
3
   0.9%
9
   1.4%
White
269
  81.5%
263
  80.2%
532
  80.9%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
34
  10.3%
36
  11.0%
70
  10.6%
Geographic Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 330 participants 328 participants 658 participants
Europe
167
  50.6%
153
  46.6%
320
  48.6%
North America
118
  35.8%
122
  37.2%
240
  36.5%
Asia Pacific
39
  11.8%
47
  14.3%
86
  13.1%
Latin America
6
   1.8%
6
   1.8%
12
   1.8%
Randomization Stratification Factors per CRF  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 330 participants 328 participants 658 participants
Prior VEGFR-TKI = 1
235
  71.2%
229
  69.8%
464
  70.5%
Prior VEGFR-TKI ≥ 2
95
  28.8%
99
  30.2%
194
  29.5%
MSKCC risk factors = 0
150
  45.5%
150
  45.7%
300
  45.6%
MSKCC risk factors = 1
139
  42.1%
135
  41.2%
274
  41.6%
MSKCC risk factors = 2 or 3
41
  12.4%
43
  13.1%
84
  12.8%
Prior VEGFR-TKI = 1, MSKCC risk factors = 0
102
  30.9%
100
  30.5%
202
  30.7%
Prior VEGFR-TKI = 1, MSKCC risk factors = 1
107
  32.4%
103
  31.4%
210
  31.9%
Prior VEGFR-TKI = 1, MSKCC risk factors = 2 or 3
26
   7.9%
26
   7.9%
52
   7.9%
Prior VEGFR-TKI ≥ 2, MSKCC risk factors =0
48
  14.5%
50
  15.2%
98
  14.9%
Prior VEGFR-TKI ≥ 2, MSKCC risk factors = 1
32
   9.7%
32
   9.8%
64
   9.7%
Prior VEGFR-TKI ≥ 2, MSKCC risk factors = 2 or 3
15
   4.5%
17
   5.2%
32
   4.9%
Karnofsky performance status (KPS)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 330 participants 328 participants 658 participants
100 (normal activity)
99
  30.0%
74
  22.6%
173
  26.3%
90 (normal activity, minor signs and symptoms)
127
  38.5%
142
  43.3%
269
  40.9%
80 (normal w/effort, minor signs/symptoms)
75
  22.7%
90
  27.4%
165
  25.1%
70 (unable to work, cares for self)
29
   8.8%
22
   6.7%
51
   7.8%
Heng Prognostic Criteria  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 330 participants 328 participants 658 participants
0 adverse factors (favorable risk)
66
  20.0%
62
  18.9%
128
  19.5%
1-2 adverse factors (intermediate risk)
210
  63.6%
214
  65.2%
424
  64.4%
3-6 adverse factors (poor risk)
54
  16.4%
52
  15.9%
106
  16.1%
1.Primary Outcome
Title Progression-free Survival (PFS)
Hide Description The primary analysis of PFS is the time from randomization to date of first documented tumor progression as determined by investigator (per RECIST 1.1 criteria) or death due to any cause, whichever occurred first. A Kaplan-Meier analysis was performed to estimate the median duration.
Time Frame PFS is measured from the date of randomization until the date of first documented disease progression or date of death from any cause as determined by the Independent Radiology Committee (IRC) per RECIST 1.1, assessed for up to 17 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The pre-specified primary analysis of PFS was based on the first 375 randomized subjects (187 cabozantinib and 188 everolimus).
Arm/Group Title Cabozantinib (XL184) Everolimus (Afinitor)
Hide Arm/Group Description:

Cabozantinib (XL184) 60 mg tablet once daily.

Cabozantinib tablets

Everolimus (Afinitor) 10 mg tablet once daily.

Everolimus (Afinitor) tablets

Overall Number of Participants Analyzed 187 188
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: months
7.4
(5.6 to 9.1)
3.8
(3.7 to 5.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cabozantinib (XL184), Everolimus (Afinitor)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments The Log-Rank Test was stratified by the Memorial Sloan-Kettering Cancer Center (MSKCC) group and number of prior VEGFR TKIs.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.45 to 0.74
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall Survival (OS) is defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS was calculated using Kaplan-Meier estimates. Interim analyses for OS occurred after 320 deaths (78% of the total OS events needed for final analysis).
Time Frame OS was measured from the time of randomization until 320 deaths, approximately 28 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat (ITT) population was used and included 658 randomized subjects (330 cabozantinib, 328 everolimus) in the second interim analysis with a cutoff date of 31 December 2015.
Arm/Group Title Cabozantinib (XL184) Everolimus (Afinitor)
Hide Arm/Group Description:

Cabozantinib (XL184) 60 mg tablet once daily.

Cabozantinib tablets

Everolimus (Afinitor) 10 mg tablet once daily.

Everolimus (Afinitor) tablets

Overall Number of Participants Analyzed 330 228
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: months
21.4 [1] 
(18.7 to NA)
16.5
(14.7 to 18.8)
[1]
Too few events to estimate the upper limit of the confidence interval.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cabozantinib (XL184), Everolimus (Afinitor)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Log Rank
Comments The Log-Rank test was stratified by the Memorial Sloan-Kettering Cancer Center (MSKCC) risk group and number of prior VEGFR TKIs.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.53 to 0.83
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Objective Response Rate (ORR)
Hide Description Objective Response Rate (ORR) is the number of participants with a best response of complete response (CR) or partial response (PR) divided by number of randomized participants. ORR was assessed by the Independent Radiology Committee (IRC) per RECIST 1.1 which was confirmed by a subsequent visit >= 28 days later, and was analyzed in the Intent to Treat (ITT) population at the time of the primary analysis of Progression Free Survival (PFS). The data cutoff date was 22 May 2015.
Time Frame ORR was assessed at 8 weeks post-randomization, every 8 weeks for 12 months, and every 12 weeks until date of disease progression or death, up to May 2015 (approximately 21 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis of ORR was performed in the ITT population (all randomized: 330 cabozantinib, 328 everolimus) based upon response determined by Independent Radiology Committee (IRC) per RECIST 1.1.
Arm/Group Title Cabozantinib (XL184) Everolimus (Afinitor)
Hide Arm/Group Description:

Cabozantinib (XL184) 60 mg tablet once daily.

Cabozantinib tablets

Everolimus (Afinitor) 10 mg tablet once daily.

Everolimus (Afinitor) tablets

Overall Number of Participants Analyzed 330 328
Measure Type: Number
Unit of Measure: percentage of participants
17 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cabozantinib (XL184), Everolimus (Afinitor)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Time Frame 08 August 2013 - 22 May 2015
Adverse Event Reporting Description The safety data includes subjects who were randomized and treated. Of 658 patients, 330 were randomized to receive cabozantinib and 328 everolimus. Five subjects in the everolimus arm were randomized but not treated. One subject randomized to the everolimus arm received cabozantinib only as study treatment and was evaluated in the cabozantinib arm for the Safety population (331 cabozantinib, 322 everolimus).
 
Arm/Group Title Cabozantinib (XL184) Everolimus (Afinitor)
Hide Arm/Group Description

Cabozantinib (XL184) 60 mg tablet once daily.

Cabozantinib tablets

Everolimus (Afinitor) 10 mg tablet once daily.

Everolimus (Afinitor) tablets

All-Cause Mortality
Cabozantinib (XL184) Everolimus (Afinitor)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Cabozantinib (XL184) Everolimus (Afinitor)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   131/331 (39.58%)      139/322 (43.17%)    
Blood and lymphatic system disorders     
Abdominal lymphadenopathy  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Anaemia  1  6/331 (1.81%)  6 12/322 (3.73%)  12
Haemorrhagic anaemia  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Lymphadenopathy  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Cardiac disorders     
Acute coronary syndrome  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Atrial fibrillation  1  2/331 (0.60%)  2 3/322 (0.93%)  3
Cardiac failure  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Cardiac failure congestive  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Cardiac tamponade  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Conduction disorder  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Myocardial infarction  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Palpitations  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Pericardial effusion  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Ventricular arrhythmia  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Ear and labyrinth disorders     
Tinnitus  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Endocrine disorders     
Adrenal Insufficiency  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Hypercalcaemia of Malignancy  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Gastrointestinal disorders     
Abdominal Pain  1  10/331 (3.02%)  10 2/322 (0.62%)  2
Abdominal Pain Upper  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Anal Fistula  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Ascites  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Colitis  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Colitis Ulcerative  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Constipation  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Diarrhoea  1  7/331 (2.11%)  7 2/322 (0.62%)  2
Faecaloma  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Gastric Haemorrhage  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Gastritis  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Gastrointestinal Perforation  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Inguinal Hernia  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Intestinal Perforation  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Nausea  1  7/331 (2.11%)  7 2/322 (0.62%)  2
Oesophageal Pain  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Pancreatitis  1  2/331 (0.60%)  2 1/322 (0.31%)  1
Pancreatitis Acute  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Proctitis  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Rectal Haemorrhage  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Small Intestine Obstruction  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Small Intestinal Perforation  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Stomatitis  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Swollen Tongue  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Upper Gastrointestinal Haemorrhage  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Vomiting  1  6/331 (1.81%)  6 4/322 (1.24%)  4
General disorders     
Asthenia  1  4/331 (1.21%)  4 1/322 (0.31%)  1
Death  1  2/331 (0.60%)  2 0/322 (0.00%)  0
Device Occlusion  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Fatigue  1  6/331 (1.81%)  6 5/322 (1.55%)  5
General Physical Health Deterioration  1  4/331 (1.21%)  4 6/322 (1.86%)  6
Generalised Oedema  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Hypothermia  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Local Swelling  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Malaise  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Mucosal Inflammation  1  0/331 (0.00%)  0 2/322 (0.62%)  2
Mutli-Organ Failure  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Non-Cardiac Chest Pain  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Oedema  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Oedema Peripheral  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Pain  1  5/331 (1.51%)  5 4/322 (1.24%)  4
Pyrexia  1  3/331 (0.91%)  3 4/322 (1.24%)  4
Ulcer Haemorrhage  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Hepatobiliary disorders     
Bile Duct Obstruction  1  2/331 (0.60%)  2 0/322 (0.00%)  0
Cholangitis  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Cholecystitis  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Cholecystitis Acute  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Hepatitis Cholestatic  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Infections and infestations     
Abdominal Abscess  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Abscess Neck  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Acute Sinusitis  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Anal Abscess  1  2/331 (0.60%)  2 0/322 (0.00%)  0
Anorectal Cellulitis  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Appendicitis  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Appendicitis Perforated  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Aspergillus Infection  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Bacteraemia  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Bacterial Sepsis  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Bronchitis  1  1/331 (0.30%)  1 2/322 (0.62%)  2
Bronchopneumonia  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Device Related Infection  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Diverticulitis  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Empyema  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Gastroenteritis  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Implant Site Infection  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Infection  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Kidney Infection  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Klebsiella Infection  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Lower Respiratory Tract Infection  1  1/331 (0.30%)  1 3/322 (0.93%)  3
Lung Infection  1  2/331 (0.60%)  2 1/322 (0.31%)  1
Otitis Externa  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Periorbital Cellulitis  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Peritonitis  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Peritonitis Bacterial  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Pleural Infection  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Pneumocystis Jirovecii Pneumonia  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Pneumonia  1  6/331 (1.81%)  6 13/322 (4.04%)  13
Pyelonephritis  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Respiratory Tract Infection  1  0/331 (0.00%)  0 2/322 (0.62%)  2
Sepsis  1  1/331 (0.30%)  1 3/322 (0.93%)  3
Septic Shock  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Skin Infection  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Tuberculosis  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Urinary Tract Infection  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Urosepsis  1  2/331 (0.60%)  2 0/322 (0.00%)  0
Viral Pharyngitis  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Vulval Cellulitis  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Wound Infection  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Injury, poisoning and procedural complications     
Acetabulum Fracture  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Contusion  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Extradural Haematoma  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Fall  1  3/331 (0.91%)  3 2/322 (0.62%)  2
Femoral Neck Fracture  1  0/331 (0.00%)  0 2/322 (0.62%)  2
Foreign Body in Eye  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Fracture  1  2/331 (0.60%)  2 0/322 (0.00%)  0
Humerus Fracture  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Incisional Hernia  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Post Procedural Haemorrhage  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Rib Fracture  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Stress Fracture  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Thoracic Vertebral Fracture  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Investigations     
Blood Bilirubin Increased  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Blood Cholesterol Increased  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Haemoglobin Decreased  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Weight Decreased  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Metabolism and nutrition disorders     
Decreased Appetite  1  2/331 (0.60%)  2 1/322 (0.31%)  1
Dehydration  1  3/331 (0.91%)  3 7/322 (2.17%)  7
Diabetes Mellitus  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Diabetes Mellitus Inadequate Control  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Electrolyte Imbalance  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Hypercalcaemia  1  4/331 (1.21%)  4 4/322 (1.24%)  4
Hyperglycaemia  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Hyperkalaemia  1  2/331 (0.60%)  2 2/322 (0.62%)  2
Hypocalcaemia  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Hypokalaemia  1  2/331 (0.60%)  2 0/322 (0.00%)  0
Hypomagnesaemia  1  4/331 (1.21%)  4 0/322 (0.00%)  0
Hyponatraemia  1  4/331 (1.21%)  4 2/322 (0.62%)  2
Type 2 Diabetes Mellitus  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Back Pain  1  6/331 (1.81%)  6 4/322 (1.24%)  4
Flank Pain  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Haemarthrosis  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Lumbar Spinal Stenosis  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Musculoskeletal Chest Pain  1  1/331 (0.30%)  1 2/322 (0.62%)  2
Osteolysis  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Osteonecrosis of Jaw  1  1/331 (0.30%)  1 2/322 (0.62%)  2
Pain in Extremity  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Pathological Fracture  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenocarcinoma  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Adenocarcinoma of Colon  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Chronic Lymphocytic Leukaemia  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Leiomyoma  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Malignant Melanoma  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Malignant Neoplasm of Orbit  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Metastases to Bone  1  2/331 (0.60%)  2 2/322 (0.62%)  2
Metastases to Central Nervous System  1  1/331 (0.30%)  1 5/322 (1.55%)  5
Metastases to Ovary  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Metastases to Pelvis  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Metatases to Spine  1  2/331 (0.60%)  2 2/322 (0.62%)  2
Metatases to Testicle  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Metastatic Pain  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Metastatic Renal Cell Carcinoma  1  2/331 (0.60%)  2 1/322 (0.31%)  1
Renal Cancer  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Renal Cell Carcinoma  1  11/331 (3.32%)  11 11/322 (3.42%)  11
Tumour Associated Fever  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Tumour Thrombosis  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Nervous system disorders     
Carotid Artery Occlusion  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Carotid Artery Thrombosis  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Cerebral Haematoma  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Cerebrovascular Disorder  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Cognitive Disorder  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Convulsion  1  2/331 (0.60%)  2 0/322 (0.00%)  0
Dizziness  1  2/331 (0.60%)  2 1/322 (0.31%)  1
Epilepsy  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Intracranial Venous Sinus Thrombosis  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Miller Fisher Syndrome  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Somnolence  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Spinal Cord Compression  1  1/331 (0.30%)  1 4/322 (1.24%)  4
Syncope  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Transient Ischaemic Attack  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Psychiatric disorders     
Confusional State  1  2/331 (0.60%)  2 1/322 (0.31%)  1
Delirium  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Renal and urinary disorders     
Haematuria  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Renal Failure  1  1/331 (0.30%)  1 2/322 (0.62%)  2
Renal Failure Acute  1  0/331 (0.00%)  0 5/322 (1.55%)  5
Renal Haemorrhage  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Renal Impairment  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Renal pain  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Reproductive system and breast disorders     
Pelvic Pain  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Prostatitis  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Respiratory, thoracic and mediastinal disorders     
Acute Respiratory Failure  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Cough  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Dyspnoea  1  6/331 (1.81%)  6 13/322 (4.04%)  13
Haemoptysis  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Hydrothorax  1  0/331 (0.00%)  0 3/322 (0.93%)  3
Hypoxia  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Interstitial Lung Disease  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Obstructive Airways Disorder  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Pleural Effusion  1  10/331 (3.02%)  10 6/322 (1.86%)  6
Pneumonia Aspiration  1  0/331 (0.00%)  0 3/322 (0.93%)  3
Pneumonitis  1  0/331 (0.00%)  0 8/322 (2.48%)  8
Pneumothorax  1  4/331 (1.21%)  4 1/322 (0.31%)  1
Pulmonary Embolism  1  6/331 (1.81%)  6 1/322 (0.31%)  1
Pulmonary Haemorrhage  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Respiratory Distress  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Respiratory Failure  1  1/331 (0.30%)  1 1/322 (0.31%)  1
Skin and subcutaneous tissue disorders     
Dermatitis Bullous  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Hyperhidrosis  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Pruritus  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Rash  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Rash Maculo-Papular  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Vascular disorders     
Circulatory Collapse  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Deep Vein Thrombosis  1  4/331 (1.21%)  4 0/322 (0.00%)  0
Hypertension  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Orthostatic Hypotension  1  0/331 (0.00%)  0 1/322 (0.31%)  1
Pelvic Venous Thrombosis  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Peripheral Ischaemia  1  1/331 (0.30%)  1 0/322 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cabozantinib (XL184) Everolimus (Afinitor)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   328/331 (99.09%)      270/322 (83.85%)    
Endocrine disorders     
Hypothyroidism  1  68/331 (20.54%)  68 2/322 (0.62%)  2
Gastrointestinal disorders     
Abdominal Pain  1  50/331 (15.11%)  50 30/322 (9.32%)  30
Abdominal Pain Upper  1  26/331 (7.85%)  26 7/322 (2.17%)  7
Constipation  1  83/331 (25.08%)  83 61/322 (18.94%)  61
Diarrhoea  1  245/331 (74.02%)  245 88/322 (27.33%)  88
Dyspepsia  1  40/331 (12.08%)  40 15/322 (4.66%)  15
Flatulence  1  32/331 (9.67%)  32 6/322 (1.86%)  6
Nausea  1  164/331 (49.55%)  164 89/322 (27.64%)  89
Vomiting  1  105/331 (31.72%)  105 44/322 (13.66%)  44
General disorders     
Fatigue  1  185/331 (55.89%)  185 149/322 (46.27%)  149
Investigations     
Alanine Aminotransferase Increased  1  53/331 (16.01%)  53 19/322 (5.90%)  19
Aspartate Aminotransferase Increased  1  58/331 (17.52%)  58 18/322 (5.59%)  18
Blood Thyrpod Stimulating Hormone Increased  1  23/331 (6.95%)  23 3/322 (0.93%)  3
Weight Decreased  1  104/331 (31.42%)  104 39/322 (12.11%)  39
Metabolism and nutrition disorders     
Decreased Appetite  1  152/331 (45.92%)  152 108/322 (33.54%)  108
Hypomagnesaemia  1  50/331 (15.11%)  50 5/322 (1.55%)  5
Musculoskeletal and connective tissue disorders     
Muscle Spasms  1  42/331 (12.69%)  42 16/322 (4.97%)  16
Pain in Extremity  1  46/331 (13.90%)  46 25/322 (7.76%)  25
Nervous system disorders     
Dysgeusia  1  78/331 (23.56%)  78 30/322 (9.32%)  30
Respiratory, thoracic and mediastinal disorders     
Dysphonia  1  66/331 (19.94%)  66 12/322 (3.73%)  12
Skin and subcutaneous tissue disorders     
Palmar-Plantar Erythrodysaesthesia Syndrome  1  139/331 (41.99%)  139 19/322 (5.90%)  19
Vascular disorders     
Hypertension  1  122/331 (36.86%)  122 23/322 (7.14%)  23
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
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.
Our agreements with investigators vary; constant is our right to review results communications prior to public release, and embargo communications for a period of ≤60 days from submittal for review. We do not prohibit investigators from publishing, but we may require previously undisclosed confidential information, other than study results, to be removed from publications, and single-center publications are postponed until after publication of the trial’s primary multicenter publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Exelixis Medical Information
Organization: Exelixis, Inc.
Phone: 855-292-3935
EMail: druginfo@exelixis.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT01865747     History of Changes
Other Study ID Numbers: XL184-308
First Submitted: May 21, 2013
First Posted: May 31, 2013
Results First Submitted: April 21, 2017
Results First Posted: July 18, 2017
Last Update Posted: May 22, 2018