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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Exelixis
ClinicalTrials.gov Identifier:
NCT00704730
First received: June 23, 2008
Last updated: August 29, 2014
Last verified: August 2014
Results First Received: April 8, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Thyroid Cancer
Interventions: Drug: XL184
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First patient enrolled 10 September 2008, last patient enrolled 27 February 2011. Data cut off date 15 June 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
XL184 (Cabozantinib) XL184 175 mg L-malate salt weight; 138 mg freebase equivalent weight, oral capsules once daily
Placebo oral capsules once daily

Participant Flow:   Overall Study
    XL184 (Cabozantinib)     Placebo  
STARTED     219 [1]   111 [1]
COMPLETED     98 [2]   15 [2]
NOT COMPLETED     121     96  
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.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
XL184 (Cabozantinib) XL184 175 mg L-malate salt weight; 138 mg freebase equivalent weight, oral capsules once daily
Placebo oral capsules once daily
Total Total of all reporting groups

Baseline Measures
    XL184 (Cabozantinib)     Placebo     Total  
Number of Participants  
[units: participants]
  219     111     330  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     172     86     258  
>=65 years     47     25     72  
Age  
[units: years]
Mean ± Standard Deviation
  54.4  ± 13.33     53.8  ± 13.39     54.2  ± 13.33  
Gender  
[units: participants]
     
Female     68     41     109  
Male     151     70     221  
Region of Enrollment  
[units: 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  



  Outcome Measures
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1.  Primary:   Progression-Free Survival (PFS)   [ 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. ]

2.  Secondary:   Overall Survival (OS) With XL184 Compared With Placebo   [ 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. ]

3.  Secondary:   Objective Response Rate (ORR)   [ 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. ]

4.  Secondary:   Duration of Objective Response (OR): Independent Radiology Committee (IRC) Determined   [ 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. ]

5.  Secondary:   Biochemical Response Calcitonin (CTN) %   [ 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. ]

6.  Secondary:   Biochemical Response Carcinoembryonic Antigen (CEA) %   [ 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. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Yifah Yaron, MD Senior Director, Clinical Research, Clinical Development
Organization: Exelixis, Inc
phone: 650-837-7678
e-mail: yyaron@exelixis.com


No publications provided by Exelixis

Publications automatically indexed to this study:

Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT00704730     History of Changes
Other Study ID Numbers: XL184-301
Study First Received: June 23, 2008
Results First Received: April 8, 2014
Last Updated: August 29, 2014
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Belgium: Federal Agency for Medicinal Products and Health Products
Denmark: Danish Medicines Agency
Netherlands: Medicines Evaluation Board (MEB)
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Spanish Agency of Medicines
Canada: Health Canada
Israel: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Poland: Ministry of Health
Austria: Agency for Health and Food Safety
Italy: The Italian Medicines Agency
Greece: National Organization of Medicines
India: Drugs Controller General of India
Portugal: National Pharmacy and Medicines Institute
South Korea: Korea Food and Drug Administration (KFDA)
Russia: Ministry of Health of the Russian Federation
Chile: Comisión Nacional de Investigación Científica y Tecnológica
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Brazil: Ministry of Health
Switzerland: Swissmedic
Saudi Arabia: Ethics Committee