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Cilengitide in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) (ADVANTAGE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00705016
First received: June 24, 2008
Last updated: March 28, 2014
Last verified: March 2014
Results First Received: March 28, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Squamous Cell Cancer
Interventions: Drug: Cilengitide 2000 mg once weekly
Drug: Cilengitide 2000 mg twice weekly
Drug: Cetuximab
Drug: 5-fluorouracil (5-FU)
Drug: Cisplatin

  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
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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
Cilengitide 2000 mg Once Weekly+Cetuximab+5-FU+Cisplatin Cilengitide 500 milligram (mg) intravenous infusion over 60 minutes, daily from Day 1 to 4 of the first week of each 3-week cycle, subsequently followed by cilengitide 2000 mg once weekly along with cetuximab 250 milligram per square meter (mg/m^2) intravenous infusion (initial starting dose of 400 mg/m^2) once weekly, 5-fluorouracil (5-FU) 1000 mg/m^2 intravenous continuous infusion daily from Day 1 to 4 and cisplatin 100 mg/m^2 intravenous infusion over 60 minutes on Day 1, of each 3-week treatment cycle for a total of 6 cycles (18 weeks) or until progressive disease (PD), unacceptable toxicity or withdrawal for any other reason. After 6 cycles, participants received cilengitide 2000 mg once weekly along with cetuximab 250 mg/m^2 intravenous infusion until PD, unacceptable toxicity or withdrawal for any other reason.
Cilengitide 2000 mg Twice Weekly+Cetuximab+5-FU+Cisplatin Cilengitide 2000 mg intravenous infusion over 60 minutes twice weekly along with cetuximab 250 mg/m^2 intravenous infusion (initial starting dose of 400 mg/m^2) once weekly, 5-fluorouracil (5-FU) 1000 mg/m^2 intravenous continuous infusion daily from Day 1 to 4 and cisplatin 100 mg/m^2 intravenous infusion over 60 minutes on Day 1, of each 3-week treatment cycle for a total of 6 cycles (18 weeks) or until PD, unacceptable toxicity or withdrawal for any other reason. After 6 cycles, participants received cilengitide 2000 mg once weekly along with cetuximab 250 mg/m^2 intravenous infusion until PD, unacceptable toxicity or withdrawal for any other reason.
Cetuximab+5-FU+Cisplatin Cetuximab 250 mg/m^2 intravenous infusion (initial starting dose of 400 mg/m^2) once weekly along with 5-fluorouracil (5-FU) 1000 mg/m^2 intravenous continuous infusion daily from Day 1 to 4 and cisplatin 100 mg/m^2 intravenous infusion over 60 minutes on Day 1, of each 3-week treatment cycle for a total of 6 cycles (18 weeks) or until PD, unacceptable toxicity or withdrawal for any other reason. After 6 cycles, participants received cetuximab 250 mg/m^2 intravenous infusion until PD, unacceptable toxicity or withdrawal for any other reason.

Participant Flow:   Overall Study
    Cilengitide 2000 mg Once Weekly+Cetuximab+5-FU+Cisplatin   Cilengitide 2000 mg Twice Weekly+Cetuximab+5-FU+Cisplatin   Cetuximab+5-FU+Cisplatin
STARTED   62   60   62 
COMPLETED   2   2   4 
NOT COMPLETED   60   58   58 
Adverse Event                6                11                10 
Death                5                7                5 
Protocol Violation                0                1                1 
Withdrawal by Subject                4                3                2 
Progressive Disease                33                29                33 
Symptomatic Deterioration                3                1                1 
Unspecified                9                6                6 



  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.
Intention-to-treat (ITT) population included all participants who were randomized to trial treatment.

Reporting Groups
  Description
Cilengitide 2000 mg Once Weekly+Cetuximab+5-FU+Cisplatin Cilengitide 500 milligram (mg) intravenous infusion over 60 minutes, daily from Day 1 to 4 of the first week of each 3-week cycle, subsequently followed by cilengitide 2000 mg once weekly along with cetuximab 250 milligram per square meter (mg/m^2) intravenous infusion (initial starting dose of 400 mg/m^2) once weekly, 5-fluorouracil (5-FU) 1000 mg/m^2 intravenous continuous infusion daily from Day 1 to 4 and cisplatin 100 mg/m^2 intravenous infusion over 60 minutes on Day 1, of each 3-week treatment cycle for a total of 6 cycles (18 weeks) or until progressive disease (PD), unacceptable toxicity or withdrawal for any other reason. After 6 cycles, participants received cilengitide 2000 mg once weekly along with cetuximab 250 mg/m^2 intravenous infusion until PD, unacceptable toxicity or withdrawal for any other reason.
Cilengitide 2000 mg Twice Weekly+Cetuximab+5-FU+Cisplatin Cilengitide 2000 mg intravenous infusion over 60 minutes twice weekly along with cetuximab 250 mg/m^2 intravenous infusion (initial starting dose of 400 mg/m^2) once weekly, 5-fluorouracil (5-FU) 1000 mg/m^2 intravenous continuous infusion daily from Day 1 to 4 and cisplatin 100 mg/m^2 intravenous infusion over 60 minutes on Day 1, of each 3-week treatment cycle for a total of 6 cycles (18 weeks) or until PD, unacceptable toxicity or withdrawal for any other reason. After 6 cycles, participants received cilengitide 2000 mg once weekly along with cetuximab 250 mg/m^2 intravenous infusion until PD, unacceptable toxicity or withdrawal for any other reason.
Cetuximab+5-FU+Cisplatin Cetuximab 250 mg/m^2 intravenous infusion (initial starting dose of 400 mg/m^2) once weekly along with 5-fluorouracil (5-FU) 1000 mg/m^2 intravenous continuous infusion daily from Day 1 to 4 and cisplatin 100 mg/m^2 intravenous infusion over 60 minutes on Day 1, of each 3-week treatment cycle for a total of 6 cycles (18 weeks) or until PD, unacceptable toxicity or withdrawal for any other reason. After 6 cycles, participants received cetuximab 250 mg/m^2 intravenous infusion until PD, unacceptable toxicity or withdrawal for any other reason.
Total Total of all reporting groups

Baseline Measures
   Cilengitide 2000 mg Once Weekly+Cetuximab+5-FU+Cisplatin   Cilengitide 2000 mg Twice Weekly+Cetuximab+5-FU+Cisplatin   Cetuximab+5-FU+Cisplatin   Total 
Overall Participants Analyzed 
[Units: Participants]
 62   60   62   184 
Age [1] 
[Units: Years]
Mean (Standard Deviation)
 59.1  (7.4)   56.8  (7.9)   58.6  (8.1)   58.2  (7.8) 
[1] Out of a total of 62 participants in Cetuximab + 5-FU + Cisplatin group, data for baseline measure (age) was available for 61 participants only.
Age, Customized [1] 
[Units: Participants]
       
Less than (<) 65 years   47   48   46   141 
Greater than or equal to (>=) 65 years   15   12   15   42 
[1] Out of a total of 62 participants in Cetuximab + 5-FU + Cisplatin group, data for baseline measure (age) was available for 61 participants only.
Gender 
[Units: Participants]
       
Female   8   11   6   25 
Male   54   49   56   159 
Karnofsky Performance Status [1] 
[Units: Participants]
       
< 80 (Karnofsky Score)   7   6   5   18 
>= 80 (Karnofsky Score)   55   54   57   166 
[1] Karnofsky performance status score ranged from 100 to 0; 100: Normal; 90: Able to Carry on normal Activity; 80: Normal Activity with Effort; Some Signs or Symptoms of Disease; 70: Cares for Self, Unable to Carry on Normal Activity or to Do Active Work; 60: Requires Occasional Assistance but is Able to Care for Most of Needs; 50: Requires Considerable Assistance and Frequent Medical Care; 40: Disabled, Requires Special Care and Assistance; 30: Severely Disabled; Hospitalization Indicated Although Death is Not Imminent; 20: Very Sick; 10: Moribund, Fatal Processes Progressing Rapidly; 0: Death.
Extent of disease at study entry 
[Units: Participants]
       
Recurrence   30   32   31   93 
Distant Metastasis   32   28   31   91 
Tumor Grade [1] 
[Units: Participants]
       
Well or moderately differentiated   46   39   35   120 
Poorly differentiated   11   19   22   52 
[1] Out of a total of 62 participants in Cilengitide 2000 mg once weekly + Cetuximab + 5-FU + Cisplatin group, 60 participants in Cilengitide 2000 mg twice weekly + Cetuximab + 5-FU + Cisplatin group, and 62 participants in Cetuximab + 5-FU + Cisplatin group, data for baseline measure (Tumor grade) was available for 57, 58 and 57 participants only, respectively. Tumor grades were divided in to well or moderately differentiated and poorly differentiated.
Site of origin of tumor 
[Units: Participants]
       
Oropharynx   25   23   21   69 
Hypopharynx   10   14   14   38 
Larynx   14   15   13   42 
Oral cavity   11   6   11   28 
Other, including non-classifiable   2   2   3   7 


  Outcome Measures
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1.  Primary:   Progression-free Survival (PFS) Time: Investigator Read   [ Time Frame: Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011) ]

2.  Secondary:   Overall Survival (OS) Time   [ Time Frame: Time from randomization to death, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011) ]

3.  Secondary:   Best Overall Response (BOR) Rate   [ Time Frame: Evaluations will be performed every 6 weeks until progression reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011) ]

4.  Secondary:   Disease Control Rate   [ Time Frame: Evaluations will be performed every 6 weeks until progression reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011) ]

5.  Secondary:   Time to Treatment Failure (TTF)   [ Time Frame: Time from randomization to disease progression, death or last tumor assessment, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011) ]

6.  Secondary:   Duration of Response   [ Time Frame: Time from first assessment of CR or PR until PD, death or last tumor assessment, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011) ]

7.  Secondary:   Safety - Number of Participants Experiencing Any Adverse Event   [ Time Frame: Time from first assessment of CR or PR until PD, death or last tumor assessment, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011) ]


  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
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  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 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.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Merck KGaA Communication Center
Organization: Merck Serono, a division of Merck KGaA
phone: +49-6151-72-5200
e-mail: service@merckgroup.com


Publications of Results:

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT00705016     History of Changes
Other Study ID Numbers: EMR 200052-013
2008-000615-15 ( EudraCT Number )
Study First Received: June 24, 2008
Results First Received: March 28, 2014
Last Updated: March 28, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Austria: Agency for Health and Food Safety
Switzerland: Swissmedic
Spain: Spanish Agency of Medicines
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products