| General information |
| Database: | DB00325 |
| Objective: | Novel therapies are needed to improve the poor prognosis of patients with recurrent and/or metastatic squamous cell cancer of the head and neck (SCCHN). |
| Authors: | Vermorken JB, et al |
| Title: | Phase I/II trial of cilengitide with cetuximab, cisplatin and 5fluorouracil in recurrent and/or metastatic squamous cell cancer of the head and neck: findings of the phase I part. |
| Journal: | Br J Cancer. |
| Year: | 2011 |
| PMID: | 21540865 |
| 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: | cilengitide with cetuximab, cisplatin and 5fluorouracil |
| Study Type: | phase I/II, multicentre study |
| Key Patients Feature: | Inclusion criteria for the study included: (i) adults aged X18 years;(ii) a histologically or cytologically confirmed diagnosis ofrecurrent and/or metastatic SCCHN that was not suitable for localtherapy; (iii) patients with X1 measurable lesion by eithercomputerised tomography (CT) or magnetic resonance imaging(MRI); (iv) performance status X70 on the Karnofsky performance status scale; and (v) 0-1 on the Eastern CooperativeOncology Group scale. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | the phase I part tested cilengitide (500, 1000 and 2000 mg) twice weekly with standard doses of cetuximab, cisplatin and 5fluorouracil. |
| Primary End Point: | safety and tolerability. |
| Secondary End Point: | activity in terms of response and disease control. |
| Patients Number: | 10 |
| Trial Results |
| DLT_MTD: | No doselimiting toxicities (DLTs:grade 3/4 toxicities in the first 3 weeks as defined per protocol) or deaths occurred. The most common adverse events (AEs) were constipation, rash, nausea, anorexia and fatigue. Cilengitiderelated grade 3/4 AEs, all of which occurred after the DLT observation period, were anaemia, angioedema, asthenia, mucosal inflammation, nausea and vomiting (one event per category) |
| Objective Response Rate: | Best overall tumour response was partial response (PR) for 4 out of 10 patients and stable disease (SD) for 6 out of 10 patients across all cohorts.Disease control rate (complete response, PR and SD) was 100%. |
| Disease Control Rate: | 100%. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median PFS with cilengitide in combination with cetuximab and platinumbased chemotherapy was 5.88 months (95% CI 2.96-10.15). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common adverse events (AEs) were constipation, rash, nausea, anorexia and fatigue. Cilengitiderelated grade 3/4 AEs, all of which occurred after the DLT observation period, were anaemia, angioedema, asthenia, mucosal inflammation, nausea and vomiting (one event per category). |
| Conclusions: | Cilengitide combined with cetuximab and platinumbased chemotherapy was well tolerated. No DLTs or unexpected AEs they were observed. Cilengitide 2000 mg was considered safe and was selected for the subsequent randomisedphase II part assessing progression free survival. |