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
  Purpose

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.


Condition Intervention Phase
Squamous Cell Cancer
Drug: Cilengitide 2000 mg once weekly
Drug: Cilengitide 2000 mg twice weekly
Drug: Cetuximab
Drug: 5-fluorouracil (5-FU)
Drug: Cisplatin
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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).

  • 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) ] [ Designated as safety issue: No ]
    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).

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: Yes ]
    Please refer to Adverse Events section for details of individual serious adverse events and other adverse events


Enrollment: 184
Study Start Date: October 2008
Study Completion Date: June 2013
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cilengitide 2000 mg once weekly+Cetuximab+5-FU+Cisplatin 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.
Drug: 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.
Other Name: Erbitux®
Drug: 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.
Drug: 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.
Experimental: Cilengitide 2000 mg twice weekly+Cetuximab+5-FU+Cisplatin Drug: 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.
Drug: 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.
Other Name: Erbitux®
Drug: 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.
Drug: 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.
Active Comparator: Cetuximab+5-FU+Cisplatin Drug: 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.
Other Name: Erbitux®
Drug: 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.
Drug: 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00705016

  Show 37 Study Locations
Sponsors and Collaborators
Merck KGaA
Investigators
Principal Investigator: Jan Vermorken, MD, PhD University Hospital, Antwerp
  More Information

Publications:
Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT00705016     History of Changes
Other Study ID Numbers: EMR 200052-013, 2008-000615-15
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

Keywords provided by Merck KGaA:
Randomized treatment
open-label
controlled
recurrent
metastatic
SCCHN
suitable
for local therapy

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Neoplasms, Squamous Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Cetuximab
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014