Clinical trial NCT00705016: Cilengitide in Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Squamous Cell Cancer
Keywords: Randomized treatment
open-label
controlled
recurrent
metastatic
SCCHN
suitable
for local therapy
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2008-06-25
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Progression-free Survival (PFS) Time: Investigator Read
timeFrame: 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:
measure: Overall Survival (OS) Time
timeFrame: Time from randomization to death, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)
measure: Best Overall Response (BOR) Rate
timeFrame: 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)
measure: Disease Control Rate
timeFrame: 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)
measure: Time to Treatment Failure (TTF)
timeFrame: 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)
measure: Duration of Response
timeFrame: 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)
measure: Safety - Number of Participants Experiencing Any Adverse Event
timeFrame: 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)
Other outcomes:
Locations:
city: Salzburg
country: Austria
facility: Research Site
city: Wien
country: Austria
facility: Research Site
city: Antwerp
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Edegem (Antwerp)
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Namur
country: Belgium
facility: Research Site
city: Lille cedex
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Tours
country: France
facility: Research Site
city: Vandoeuvre les Nancy
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Aachen
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Jena
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Rostock
country: Germany
facility: Research Site
city: Stuttgart
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Gyor
country: Hungary
facility: Research Site
city: Nyiregyhaza
country: Hungary
facility: Research Site
city: La Spezia
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Gliwice
country: Poland
facility: Research Site
city: Warsaw
country: Poland
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Velencia
country: Spain
facility: Research Site
city: Basel
country: Switzerland
facility: Research Site
city: Geneva
country: Switzerland
facility: Research Site
Study officials:
affiliation: University Hospital, Antwerp
name: Jan Vermorken, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.