| General information |
| Database: | DB00536 |
| Objective: | Determine the safety and efficacy of cetuximab plus paclitaxel and carboplatin as initial treatment of stage III/IV ovarian cancer. |
| Authors: | Konner J, et al |
| Title: | a phase II study of cetuximab/paclitaxel/carboplatin for the initial treatment of advancedstage ovarian, primary peritoneal, or fallopian tube cancer. |
| Journal: | Gynecol Oncol. |
| Year: | 2008 |
| PMID: | 18554700 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | ovarian, primary peritoneal, or fallopian tube carcinoma |
| Cancer Subtype: | epithelial ovarian, primary peritoneal, or fallopian tube carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | cetuximab +paclitaxel+carboplatin |
| Study Type: | phase II study |
| Key Patients Feature: | Eligible patients were 18 years and older, with a histologic diagnosis of epithelialovarian, primary peritoneal, or fallopian tube carcinoma. patients were permitted toundergo standard primary or interval debulking surgery. patients were stage III or IV, with either optimally debulked (less than and equal to 1 cm residual disease) or suboptimally debulkedtumor. Patients with any of the following histologic epithelial cell types were eligible:serous, endometrioid, clear cell, mucinous, mixed adenocarcinoma, undifferentiatedcarcinoma, transitional cell carcinoma, malignant Brenner's tumor, or adenocarcinoma not otherwise specified (NOS). Potential study patients also had to have tumortissue available for assessment of EGFR status by immunohistochemistry. Thepatients were then put through a twostep registration process. In the first step, unstained tissue slides were subject to a DAKOCytomation EGFR pharmDx test(DakoCytomation California, Inc.; Carpinteria, CA) in a central laboratory (IMPATHPredictive Oncology; New York, NY). patients were then eligible for the study if theslides exhibited positive (+1, +2, or +3) EGFR expression; details on the intensity ofEGFR immunostaining for individual patients were not collected.Other eligibility criteria included the following: a Karnofsky Performance Status(KPS) more than and equal to 70%, adequate bone marrow (absolute nutrophil count 1500/¦Ìl, platelets100, 000/¦Ìl), renal (creatinine less than and equal to 1.5¡Áinstitutional upper limit of normal) and hepatic(bilirubin less than and equal to 1.5¡Áupper limit of normal and aspartate aminotransferase [AST]less than and equal to 2.5¡Áupper limit of normal) function. Baseline neuropathy had to be less than and equal to grade 1according to the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | An initial intravenous [IV] dose of cetuximab (400 mg/m(2)) was administered over 120 min followed by weekly IV infusions of cetuximab (250 mg/m(2)) administered over 60 min. Paclitaxel (175 mg/m(2)) and carboplatin (area under the curve [AUC] of 6) were administered IV every 21 days for 6 cycles. The order of administration was cetuximab followed by paclitaxel and then carboplatin. Patients achieving a clinical complete response after 6 cycles were eligible to continue weekly cetuximab for 6 months or until toxicity or disease progression. |
| Primary End Point: | Safety. progression free survival (PFS) at 18 months |
| Secondary End Point: | NA |
| Patients Number: | 41 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 11 patients (of 41 enrolled, 27.5%) discontinued study treatment before the first tumorassessment. Of the remaining 30 patients, 21 achieved clinicalcomplete remission. Twenty patients entered the singleagentcetuximab treatmentphase. Ten patients completed all 6 cyclesof maintenance cetuximab |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 14.4 months. The PFS rates at 6, 12, 18, and 24 months were 100%, 67.2%, 38.8%, and 33.3%, respectively. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Grade 3/4 treatmentrelated toxicities included febrile neutropenia (12.5%), rash (2.5%), hypersensitivity reaction (7.5%), and hypomagnesemia (12.5%). Common grade 1/2 toxicities attributed to cetuximab included acneiform rash (82.5%), hirsutism (7.5%) or abnormal hair growth (25%), and nail disorders (22.5%), which in 3 cases resulted in the patient's discontinuation from the study. |
| Conclusions: | The combination of cetuximab with paclitaxel and carboplatin is adequately tolerated as primary therapy for ovarian cancer but did not demonstrate prolongation of PFS when compared to historical data. |