| General information |
| Database: | DB00356 |
| Objective: | To determine the tumor EGFr saturation dose with C225 and the fate of infused C225, they conducted a phase Ib study with C225 in combination with cisplatin in patients with recurrent squamous cell carcinoma of the head and neck. |
| Authors: | Shin DM, et al |
| Title: | Epidermal growth factor receptortargeted therapy with C225 and cisplatin in patients with head and neck cancer. |
| Journal: | Clin Cancer Res. |
| Year: | 2001 |
| PMID: | 11350885 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | C225
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | squamous cell carcinoma of the head and neck |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | C225 and cisplatin |
| Study Type: | Phase Ib study |
| Key Patients Feature: | patients had to have a histologicallyproven squamous cell carcinoma of the head and neck that was considered incurable with standard therapy, have a good performance status (Zubrod scale # 2), have disease accessible torepeated biopsies, have measurable disease, have adequate major organ function, and sign a written informed consent. |
| Biomarker: | EGFR |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Using tumor samples, they assessed tumor EGFr saturation by antibody using immunohistochemistry studies, the EGFr tyrosine kinase assay, and detection of the EGFr/C225 complex formation by immunoblot. Potential candidates were screened for EGFr expression in their tumors, and 12 patients who had high levels of EGFr expression and tumors easily accessible for repeated biopsies were entered at three different dose levels of C225 with a fixed dose of cisplatin. |
| Primary End Point: | the optimal biological dose of C225 (i.e., tumor EGFrsaturating dose) and to establish a safety profile of C225 in a different range of dose levels in combination with cisplatin. |
| Secondary End Point: | NA |
| Patients Number: | 12 |
| Trial Results |
| DLT_MTD: | RP2R:The loading dose of C225 at 400mg/m2 with a maintenance dose at 250 mg/m2 |
| Objective Response Rate: | Among 12 patients entered in this protocol, 9 had disease response that could be evaluated, whereas 3 did not. The overall responserate was 67% (six of nine patients). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Four patients had grade 3 or grade 4 neutropenia, and one had neutropenic fever, which may have been related to cisplatin. Among nonhematological side effects, two patients had grade 3 fatigue, one had grade 3 peripheral neuropathy, and two had grade 3 orthostatic hypotension; all may have been related to cisplatin infusion. Allergic reaction developed in two patients: one grade 2 reaction, and one grade 3. |
| Conclusions: | they conclude that infused C225 binds and significantly saturates tumor EGFr, which may render a high degree of antitumor activity, and provides a novel mechanism for targeting cancer therapy for patients who have EGFr expression in their tumors |