| General information |
| Database: | DB00339 |
| Objective: | This study was prospectively designed to examine the safety and feasibility of escalating weekly doses of cetuximab, testing the hypothesis of the relationship of dosedependent skin toxicity and efficacy. |
| Authors: | Ho C, et al |
| Title: | Escalating weekly doses of cetuximab and correlation with skin toxicity: a phase I study. |
| Journal: | Invest New Drugs. |
| Year: | 2011 |
| PMID: | 20148348 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | phase I study |
| Key Patients Feature: | Eligibility included patients with histologically or cytologically confirmed advanced solidtumors; age greater than 18 years; life expectancy of greater than 12 weeks; andperformance status 0-2. Prior chemotherapy and/or radiotherapy must have been completedat least 4 weeks and 2 weeks respectively before study entry and all significant previoustreatmentrelated toxicities had to be resolved. Patients with asymptomatic treated brainmetastasis (surgical resection or radiotherapy) were eligible for this trial if wereneurologically stable and had been off steroids for at least 4 weeks. |
| Biomarker: | all possible 12th codonactivating mutations in kras;copy numbers of the EGFR and human epidermal growth factor receptor 2 genes;Immunologic correlative studies |
| Biomark Analysis: | Correlative studies evaluating kras, EGFR FISH status and immunologic correlatives were conducted on available tumor samples. |
| Control Group Info: | single arm |
| Treatment Info: | Four dose levels were tested: Cetuximab 400 mg/m2 IV loading dose and 250, 300, 350, 400 mg/m2 weekly IV maintenance. There was no intrapatient dose escalation. Standard dose limiting toxicity criteria were used. Rash was evaluated using two additional validated dermatology methods: global acne grading scale (GAGS) and acne lesion counting (ALC). Tumor specimens and blood samples were obtained for correlative analyses. |
| Primary End Point: | MTD; |
| Secondary End Point: | this study examined the safety and feasibility to test the hypothesis that escalating doses would correlate with increased skin toxicity. |
| Patients Number: | 27 |
| Trial Results |
| DLT_MTD: | without reaching doselimiting toxicity (DLT) or the maximum tolerated dose (MTD) |
| Objective Response Rate: | In 22 evaluable patients, there was one partial response (PR) in a patient with cholangiocarcinoma (400 mg/m2) and seven patients had stable disease (SD). ALC and GAGS demonstrated no correlation with dose or response |
| Disease Control Rate: | seven patients had stable disease (SD). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The highest dose level was expanded to a total of 17 patients. Gr 3/4 toxicities included: lymphopenia (2), fatigue (2), and hypomagnesemia (2). One patient experienced a grade 3 rash (350 mg/m2). Sixty five percent of pts had a Gr 2 rash that was not dose dependent. |
| Conclusions: | Cetuximab administered at 400 mgm2 IV as a loading dose with weekly maintenance dose of 400 mgm2 is feasible and well tolerated. There was no direct correlation of the grade of rash with dose in this group of patients with heterogenous solid tumors. |