| General information |
| Database: | DB00275 |
| Objective: | Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/MSCCHN) overexpresses ¦Áv¦Â5 integrin. Cilengitide selectively inhibits ¦Áv¦Â3 and ¦Áv¦Â5 integrins and is investigated as a treatment strategy. |
| Authors: | Vermorken JB, et al |
| Title: | Cisplatin, 5fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: results of the randomizedphase I/II ADVANTAGE trial (phase II part). |
| Journal: | Ann Oncol. |
| Year: | 2014 |
| PMID: | 24567516 |
| Trial Design |
| Clinical Trial Id: | NCT00705016 |
| Agent: | cilengitide
|
| Target: | ¦Áv¦Â3 and ¦Áv¦Â5 integrins
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Cisplatin, 5fluorouracil, + cetuximab (PFE)¡Àcilengitide |
| Study Type: | a randomizedphase I/II ADVANTAGE trial |
| Key Patients Feature: | age more than and equal to 18 years; histologically or cytologically confirmed diagnosis of R/MSCCHN not suitable for local therapy; more than and equal to 1 lesion measurable by computed tomography scan or magnetic resonance imaging; Karnofsky Performance Status (KPS) more than and equal to 70; or Eastern Cooperative Oncology Group performance status 0-1. |
| Biomarker: | expression of integrins, CD31, Ki67, vascular endothelial growth factor receptor 2, vascular endothelialcadherin, type IV collagen, epidermal growth factor receptor, or p16 for human papillomavirus |
| Biomark Analysis: | None of the tested biomarkers were predictive of outcome. |
| Control Group Info: | PFE alone(arm A) versus PFE+cilengitide |
| Treatment Info: | Patients received up to six cycles of PFE alone or combined with cilengitide 2000 mg once (CIL1W) or twice (CIL2W) weekly. Thereafter, patients received maintenance therapy (cilengitide arms: cilengitide plus cetuximab; PFEalone arm: cetuximab only) until disease progression or unacceptable toxicity. |
| Primary End Point: | The primary objective was to evaluate PFS per investigator read. |
| Secondary End Point: | OS, objective response rates (ORRs), disease control rates (DCRs), duration of response, and timetotreatment failure (TTF);the safety profile; and the pharmacokinetic (PK) profile. |
| Patients Number: | 182 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | objective response rates were not improved with cilengitide (47%, 27%, and 36%, respectively). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS per investigator read was similar for CIL1W + PFE, CIL2W + PFE, and PFE alone (6.4, 5.6, and 5.7 months, respectively). |
| Median OS A vs. C: | median overall survival was not improved with cilengitide (12.4 months, 10.6 months, and 11.6 months, respectively). |
| Adverse Event(agent arm): | NA |
| Conclusions: | Neither of the cilengitidecontaining regimens demonstrated a PFS benefit over PFE alone in RMSCCHN patients. |