| General information |
| Database: | DB00535 |
| Objective: | Determine if cetuximab dose escalation to induce grade 2 rash correlates with antitumor activity and if serabased markers could predict likelihood of response. |
| Authors: | Schilder RJ, et al |
| Title: | Phase II trial of single agent cetuximab in patients with persistent or recurrent epithelial ovarian or primary peritoneal carcinoma with the potential for dose escalation to rash. |
| Journal: | Gynecol Oncol. |
| Year: | 2009 |
| PMID: | 19162309 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | ovarian carcinoma or primary peritoneal carcinoma |
| Cancer Subtype: | epithelial ovarian carcinoma or primary peritoneal carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Phase II trial |
| Key Patients Feature: | Women age 18 and older with a histologic diagnosis of persistent or recurrent epithelial ovariancarcinoma or primary peritoneal carcinoma were eligible for this trial. Patients' tumors had todemonstrate any degree of EGFR expression by immunohistochemistry using Dako kits (DakoNorth America, Carpinteria, CA) centrally performed by ImPATH Predictive Oncology (NewYork, NY). Patients were permitted to have up to two prior cytotoxic regimens and wererequired to have a platinum free interval of less than or equal to 12 months. Patients must haverecovered from recent surgery, radiation therapy or chemotherapy.Other eligibility criteria included GOG Performance Status of 02 if the patient received oneprior regimen; GOG Performance Status of 0 or 1 if the patient received 2 prior regimens;adequate bone marrow (absolute neutrophil count more than and equal to 1500/¦Ìl), renal (serum creatinineless than and equal to 1.5¡Áupper limit of normal, and hepatic (bilirubin less than and equal to 1.5¡Áupper limit of normal, hepatictransaminases and alkaline phosphatase less than and equal to 1.5¡Áupper limit of normal) function. Patientsprovided written informed consent consistent with federal, state, and institutional requirements |
| Biomarker: | Pre and posttreatment serum samples |
| Biomark Analysis: | Ninetytwo serologic markers were analyzed from 20 patients to identify markers associated with clinical activity and/or predictive of outcome. Pretreatment levels of ttheylve markers were significantly elevated in patients exhibiting PD versus SD or PR; however, changes in marker levels during the course of treatment were not significant indicators of response. |
| Control Group Info: | single arm |
| Treatment Info: | Patients with persistent/recurrent ovarian or primary peritoneal carcinoma received an initial dose of cetuximab 400 mg/m(2), then 250 mg/m(2) weekly for two 3week cycles. Patients who had stable disease (SD) and |
| Primary End Point: | safety and efficacy assessment |
| Secondary End Point: | NA |
| Patients Number: | 25 |
| Trial Results |
| DLT_MTD: | The most common grade 3toxicities were arthralgia, headache, and acneiform rash |
| Objective Response Rate: | One patient in the 06 month group achieved a PRwith a 3.5 month duration yielding an overall response rate of 4% Another 36% achieved SD (31% for the 06 month groupand 44% for the 612 months group). The median PFS was 1.8 months (95% CI 1.32.6). Themedian overall survival was 13 months (95% CI 5.6 not reached). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The median PFS was 1.8 months (95% CI 1.32.6). |
| Median OS A vs. C: | The median overall survival was 13 months (95% CI 5.6 not reached). |
| Adverse Event(agent arm): | Rash (96%) was the most common drugrelated adverse event. At first response assessment, 4 patients remained at 250 mg/m2; 8 patients were doseescalated to 325 mg/m2; of these, 4 ultimately were increased to 400 mg/m2. |
| Conclusions: | Singleagent cetuximab showed minimal activity in patients with recurrent ovarian cancer. Patients with elevated levels of 12 serologic markers at baseline were more likely to have earlier disease progression. |