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

Squamous Cell Cancer Clinical Trial

— ADVANTAGE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00705016
• Other study ID #: EMR 200052-013
• Secondary ID: 2008-000615-15
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 24, 2008
• Last updated: March 28, 2014
• Start date: October 2008
• Est. completion date: June 2013

Study information

• Verified date: March 2014
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesBelgium: Federal Agency for Medicinal Products and Health ProductsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Austria: Agency for Health and Food SafetySwitzerland: SwissmedicSpain: Spanish Agency of MedicinesHungary: National Institute of PharmacyItaly: The Italian Medicines AgencyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 184
• Est. completion date: June 2013
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Neoplasms, Squamous Cell
• Squamous Cell Cancer

Intervention

Drug:
• Cilengitide 2000 mg once weekly
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 twice weekly
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
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-fluorouracil (5-FU)
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
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.

Locations

Country	Name	City	State
Austria	Research Site	Salzburg
Austria	Research Site	Wien
Belgium	Research Site	Antwerp
Belgium	Research Site	Bruxelles
Belgium	Research Site	Edegem (Antwerp)
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Belgium	Research Site	Namur
France	Research Site	Lille cedex
France	Research Site	Montpellier
France	Research Site	Nice
France	Research Site	Toulouse
France	Research Site	Tours
France	Research Site	Vandoeuvre les Nancy
France	Research Site	Villejuif
Germany	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
Hungary	Research Site	Budapest
Hungary	Research Site	Gyor
Hungary	Research Site	Nyiregyhaza
Italy	Research Site	La Spezia
Italy	Research Site	Milano
Italy	Research Site	Napoli
Poland	Research Site	Gliwice
Poland	Research Site	Warsaw
Spain	Research Site	L'Hospitalet de Llobregat
Spain	Research Site	Madrid
Spain	Research Site	Velencia
Switzerland	Research Site	Basel
Switzerland	Research Site	Geneva

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Hungary,  Italy,  Poland,  Spain,  Switzerland, 

References & Publications (1)

Vermorken JB, Peyrade F, Krauss J, Mesía R, Remenar E, Gauler TC, Keilholz U, Delord JP, Schafhausen P, Erfán J, Brümmendorf TH, Iglesias L, Bethe U, Hicking C, Clement PM. Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recu — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	Overall Survival (OS) Time	The OS time is defined as the time from randomization to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier.	Time from randomization to death, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)	No
Secondary	Best Overall Response (BOR) Rate	The BOR rate is defined as the percentage of the participants having achieved confirmed complete response (CR) or partial response (PR) as the best overall response according to radiological assessments (based on RECIST Version 1.0).	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)	No
Secondary	Disease Control Rate	The disease control rate is defined as the percentage of participants having achieved confirmed CR, PR or stable disease (SD) as best overall response according to radiological assessments (based on RECIST Version 1.0).	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)	No
Secondary	Time to Treatment Failure (TTF)	TTF is defined as the time from randomization to date of the first occurrence of; progression, discontinuation of treatment due to progression or adverse event, start of new anticancer therapy, withdrawal of consent, or death (within 84 days of last tumor assessment). Participants without event are censored on the date of last tumor assessment.	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)	No
Secondary	Duration of Response	Duration of response is defined as the time from the first assessment of CR or PR until the date of the first occurrence of progressive disease (PD), or until the date of death.	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)	No
Secondary	Safety - Number of Participants Experiencing Any Adverse Event	Please refer to Adverse Events section for details of individual serious adverse events and other adverse events	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)	Yes