| General information |
| Database: | DB00850 |
| Objective: | In this openlabelphase I study, the maximumtolerated dose of cetuximab with concurrent chemoradiotherapy (CCRT) in stage III non small cell lung cancer together with individualized, isotoxic accelerated radiotherapy (RT) was investigated. |
| Authors: | Dingemans AM, et al |
| Title: | a phase I study of concurrent individualized, isotoxic accelerated radiotherapy and cisplatinvinorelbinecetuximab in patients with stage III non small cell lung cancer. |
| Journal: | J Thorac Oncol. |
| Year: | 2014 |
| PMID: | 24722157 |
| Trial Design |
| Clinical Trial Id: | NCT00522886 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | stage III non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | isotoxic accelerated radiotherapy + cisplatinvinorelbinecetuximab |
| Study Type: | a phase I study |
| Key Patients Feature: | Patients with stage III non small cell lung cancer, World Health Organization performance status 01, forced expiratory volume in 1 second more than 50%, carbon monoxide diffusing capacity more than 50%, weight loss less than 10%, and no severe comorbidity were enrolled. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients were treated with cetuximab 400 mg/kg d7 and 250 mg/kg weekly together with RT and cisplatin (50 mg/m d1, 8; 40 mg/m d22)vinorelbine for 5 weeks. Vinorelbine was escalated in three steps; (1) 10 mg/m d1, 8 and 8 mg/m d22, 29; (2) 20 mg/m d1, 8 and 8 mg/m d22, 29; (3) 20 mg/m d1, 8; 15 mg/m d22, 29. An individualized prescribed RT dose based on normal tissue dose constraints was applied (e.g., mean lung dose 19 Gy). |
| Primary End Point: | the maximumtolerated dose 3 months after the end of CCRT; secondary endpoints were toxicity and metabolic response as assessed by positron emission tomography. |
| Secondary End Point: | NA |
| Patients Number: | 25 |
| Trial Results |
| DLT_MTD: | Doselimiting toxicity (DLT) was not reached. The most frequent toxicity was skin rash. |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 14.8 months, 95% confidence interval 5.5 to 24.0 months; 2year PFS rate was 40% |
| Median OS A vs. C: | 21.0 months (95% confidence interval 19.0-22.8 months), and 2year survival rate was 42%. |
| Adverse Event(agent arm): | Ttheylve of 25 patients experienced greater than or equal to grade 3 toxicity (fatigue, esophagitis, skin toxicity, diarrhea, cough, dyspnea, vomiting, and pulmonary embolism |
| Conclusions: | CCRT with cetuximab and cisplatinvinorelbine is safe to deliver at full dose. The recommendedphase II dose is therefore cetuximab 400 mgm d7 and 250 mgm weekly, cisplatin 50 mgm d1, 8; 40 mgm d22 and vinorelbine 20 mgm d1, 8; 15 mgm d22, 29 for 5 weeks together with RT. |