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

Registration Number
NCT00705016
Lead Sponsor
Merck KGaA, Darmstadt, Germany
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
184
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cilengitide 2000 mg once weekly+Cetuximab+5-FU+CisplatinCilengitide 2000 mg once weekly-
Cilengitide 2000 mg once weekly+Cetuximab+5-FU+Cisplatin5-fluorouracil (5-FU)-
Cilengitide 2000 mg twice weekly+Cetuximab+5-FU+CisplatinCilengitide 2000 mg twice weekly-
Cilengitide 2000 mg twice weekly+Cetuximab+5-FU+Cisplatin5-fluorouracil (5-FU)-
Cetuximab+5-FU+Cisplatin5-fluorouracil (5-FU)-
Cilengitide 2000 mg once weekly+Cetuximab+5-FU+CisplatinCetuximab-
Cilengitide 2000 mg once weekly+Cetuximab+5-FU+CisplatinCisplatin-
Cilengitide 2000 mg twice weekly+Cetuximab+5-FU+CisplatinCetuximab-
Cilengitide 2000 mg twice weekly+Cetuximab+5-FU+CisplatinCisplatin-
Cetuximab+5-FU+CisplatinCetuximab-
Cetuximab+5-FU+CisplatinCisplatin-
Primary Outcome Measures
NameTimeMethod
Progression-free Survival (PFS) Time: Investigator ReadTime 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)

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
NameTimeMethod
Overall Survival (OS) TimeTime from randomization to death, reported between day of first participant randomized, 03 July 2009, until cut-off date (03 September 2011)

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) RateEvaluations 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)

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).

Duration of ResponseTime 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)

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.

Disease Control RateEvaluations 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)

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 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)

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.

Safety - Number of Participants Experiencing Any Adverse EventTime 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)

Please refer to Adverse Events section for details of individual serious adverse events and other adverse events

Trial Locations

Locations (1)

Research Site

🇨🇭

Geneva, Switzerland

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