Cilengitide in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
ADVANTAGE
Open-label, Randomized, Controlled Phase I/II Study of Cilengitide to Evaluate the Safety and Efficacy of the Combination of Different Regimens of Cilengitide Added to Cisplatin, 5-FU, and Cetuximab in Subjects With Recurrent/Metastatic Squamous Cell Cancer of the Head and Neck
2 other identifiers
interventional
184
9 countries
37
Brief Summary
The purpose of this open-label, randomized, controlled, Phase 1/2 study of the integrin inhibitor cilengitide is to evaluate the safety and efficacy of the combination of different regimens of cilengitide added to cisplatin, 5-fluorouracil (5-FU), and cetuximab in participants with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). The Phase 1 part was conducted in dedicated study centers. In the Phase 2 part of this trial, cilengitide is administered at two different doses to two experimental groups. The third group will only receive cisplatin, 5-FU and cetuximab. In the Phase 1 part of this trial, the dose of cilengitide in combination with cisplatin, 5-FU and cetuximab was determined. Cilengitide is an experimental anti-cancer substance interacting with so-called integrins. Integrins are protein molecules that are known to be present on the surface of certain cancer cells. Integrins are also found on certain cells that belong to growing blood vessels (endothelial cells). Integrins potentially facilitate the blood vessels' support of the tumor (angiogenesis) as well as the tumor's growth and further spread throughout the body (metastasis). By inhibiting integrins on the tumor cell surface, cilengitide potentially kills cancer cells, and potentially sensitizes cancer cells to other co-administered therapeutics. By inhibiting integrins on the endothelial cell surface, it potentially inhibits the ingrowth of additional blood vessels towards the tumor. Cilengitide is given as an intravenous infusion (given by a drip in one vein of your arm). If any unacceptable side effect occurs, treatment with the study drug will be stopped.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2008
Longer than P75 for phase_1
37 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 24, 2008
CompletedFirst Posted
Study publicly available on registry
June 25, 2008
CompletedStudy Start
First participant enrolled
October 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2013
CompletedResults Posted
Study results publicly available
April 30, 2014
CompletedApril 30, 2014
March 1, 2014
2.9 years
June 24, 2008
March 28, 2014
March 28, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS) Time: Investigator Read
The PFS is defined as the duration from randomization until radiological progression (based on response evaluation criteria in solid tumors \[RECIST\] Version 1.0) or death due to any cause. Only deaths within 84 days of last tumor assessment are considered. Participants without event are censored on the date of last tumor assessment. Investigator read is the assessment of all imaging by the treating physician at the local trial site.
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)
Secondary Outcomes (6)
Overall Survival (OS) Time
Time from randomization to death, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)
Best Overall Response (BOR) Rate
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)
Disease Control Rate
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)
Time to Treatment Failure (TTF)
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)
Duration of Response
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)
- +1 more secondary outcomes
Study Arms (3)
Cilengitide 2000 mg once weekly+Cetuximab+5-FU+Cisplatin
EXPERIMENTALCilengitide 2000 mg twice weekly+Cetuximab+5-FU+Cisplatin
EXPERIMENTALCetuximab+5-FU+Cisplatin
ACTIVE COMPARATORInterventions
Cilengitide 500 milligram (mg) will be administered as an intravenous infusion over 60 minutes, daily from Day 1 to 4 of the first week of each 3-week cycle, subsequently followed by 2000 mg dose of cilengitide on Day 8 and 15 of every 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 until PD, unacceptable toxicity or withdrawal for any other reason.
Cilengitide 2000 mg will be administered as an intravenous infusion over 60 minutes, twice weekly on Day 1, 4, 8, 11, 15, and 18 of each 3-week cycle for a total of 6 cycles (18 weeks) or until PD, unacceptable toxicity or withdrawal for any other reason. After 6 cycles, participants will receive cilengitide 2000 mg once weekly until PD, unacceptable toxicity or withdrawal for any other reason.
Cetuximab will be administered as 250 milligram per square meter (mg/m\^2) as infusion (initial starting dose of 400 mg/m\^2) on Day 1, 8 and 15 of each 3-week treatment cycle. Cetuximab will be administered 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 once weekly until PD, unacceptable toxicity or withdrawal for any other reason.
5-FU will be administered as an intravenous continuous infusion at a dose of 1000 mg/m\^2 daily from Day 1 to 4 of each 3-week treatment cycle. 5-FU will be administered for a total of 6 cycles (18 weeks), or until PD, unacceptable toxicity, or withdrawal for any other reason, whichever occur first.
Cisplatin will be administered as an intravenous infusion over 60 minutes, at a dose 100 mg/m\^2 on Day 1 of each 3-week treatment cycle. Cisplatin will be administered for a total of 6 cycles (18 weeks), or until PD, unacceptable toxicity, or withdrawal for any other reason, whichever occur first.
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed diagnosis of SCCHN
- At least one measurable lesion either by computerized tomography (CT) scan or magnetic resonance imaging (MRI)
- Karnofsky performance status (KPS) of greater than or equal to 70 or eastern cooperative oncology group performance status (ECOG PS) of 0-1 at trial entry
You may not qualify if:
- Prior systemic chemotherapy, except if given as part of a multimodal treatment for locally advanced disease, which was completed more than 6 months prior to trial entry
- Surgery (excluding prior diagnostic biopsy) or irradiation within 4 weeks before trial entry
- Nasopharyngeal Carcinoma
- Documented or symptomatic brain or leptomeningeal metastasis
- Previous treatment with epidermal growth factor receptor (EGFR) targeting therapy or signal transduction inhibitors
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (37)
Research Site
Salzburg, Austria
Research Site
Vienna, Austria
Research Site
Antwerp, Belgium
Research Site
Brussels, Belgium
Research Site
Edegem (Antwerp), Belgium
Research Site
Ghent, Belgium
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Leuven, Belgium
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Namur, Belgium
Research Site
Lille, France
Research Site
Montpellier, France
Research Site
Nice, France
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Toulouse, France
Research Site
Tours, France
Research Site
Vandœuvre-lès-Nancy, France
Research Site
Villejuif, France
Research Site
Aachen, Germany
Research Site
Berlin, Germany
Research Site
Essen, Germany
Research Site
Hamburg, Germany
Research Site
Heidelberg, Germany
Research Site
Jena, Germany
Research Site
Leipzig, Germany
Research Site
Rostock, Germany
Research Site
Stuttgart, Germany
Research Site
Budapest, Hungary
Research Site
Győr, Hungary
Research Site
Nyíregyháza, Hungary
Research Site
La Spezia, Italy
Research Site
Milan, Italy
Research Site
Napoli, Italy
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Gliwice, Poland
Research Site
Warsaw, Poland
Research Site
L'Hospitalet de Llobregat, Spain
Research Site
Madrid, Spain
Research Site
Velencia, Spain
Research Site
Basel, Switzerland
Research Site
Geneva, Switzerland
Related Publications (1)
Vermorken JB, Peyrade F, Krauss J, Mesia R, Remenar E, Gauler TC, Keilholz U, Delord JP, Schafhausen P, Erfan J, Brummendorf TH, Iglesias L, Bethe U, Hicking C, Clement PM. Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: results of the randomized phase I/II ADVANTAGE trial (phase II part). Ann Oncol. 2014 Mar;25(3):682-688. doi: 10.1093/annonc/mdu003.
PMID: 24567516RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Merck KGaA Communication Center
- Organization
- Merck Serono, a division of Merck KGaA
Study Officials
- PRINCIPAL INVESTIGATOR
Jan Vermorken, MD, PhD
University Hospital, Antwerp
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 24, 2008
First Posted
June 25, 2008
Study Start
October 1, 2008
Primary Completion
September 1, 2011
Study Completion
June 1, 2013
Last Updated
April 30, 2014
Results First Posted
April 30, 2014
Record last verified: 2014-03