| General information |
| Database: | DB00430 |
| Objective: | Epirubicin, oxaliplatin, and capecitabine (EOC) is a standard treatment in advanced esophagogastric cancer. Panitumumab (P) is a fully human, immunoglobulin G2 monoclonal antibody targeting epidermal growth factor receptor. Randomized Trial of EOC +/ Panitumumab for Advanced and Locally Advanced Esophagogastric Cancer (REAL3) will evaluate whether the addition of P to EOC improves survival in patients with advanced esophagogastric adenocarcinoma and undifferentiated carcinoma. |
| Authors: | Okines AF, et al |
| Title: | Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for advanced esophagogastric cancer: dosefinding study for the prospective multicenter, randomized, phase II/III REAL3 trial. |
| Journal: | J Clin Oncol. |
| Year: | 2010 |
| PMID: | 20679619 |
| Trial Design |
| Clinical Trial Id: | NCT00824785 |
| Agent: | panitumumab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | esophageal cancer and esophagusgastroesophageal junction cancer |
| Cancer Subtype: | advanced esophagogastric adenocarcinoma and undifferentiated carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Epirubicin, oxaliplatin, and capecitabine with or without panitumumab |
| Study Type: | prospective multicenter, randomized, phase II/III REALIII trial |
| Key Patients Feature: | patients with advanced esophagogastric adenocarcinoma and undifferentiated carcinoma |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | EOC or EOC + P |
| Treatment Info: | The original design of REAL3 added P 9 mg/kg to the standard dose of EOC (dose level [DL] + 1). Due to toxicity, a dose deescalation was made to EOC + P DL1 (epirubicin 50 mg/m(2), oxaliplatin130 mg/m(2), capecitabine 1, 000 mg/m(2)/d + P 9 mg/kg every 3 weeks). After additional toxicity was observed, the study was amended to include two additional EOC + P dose levels. Using a 3 + 3 design, doselimiting toxicities (DLTs) were assessed weekly during cycle 1. patients were randomly assigned 1:1 to EOC +/ P. |
| Primary End Point: | DLT, the recommendedphase II dose, and toxicity |
| Secondary End Point: | NA |
| Patients Number: | 29 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| 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): | Grade 3 diarrhea was reported in six of 16 patients treated with EOC P and one of 13 patients treated with EOC across all cycles. Grade 3 fatigue was documented in seven of 16 patients treated with EOC+P and three of 13 patients treated with EOC. Grade 3 or higher neutropenia was reported in six of 16 patients treated with EOC+P and two of 13 patients treated with EOC. Febrile neutropenia occurred in one patient receiving EOC and twice in one patient receiving EOC+P, despite a dose reduction after the first episode. One additional patient experienced grade 5 infection with grade 1 neutropenia (DL1). At the recommendedphase II dose (DL2), grade 3/4 toxicities reported over all cycles were uncomplicated grade 3 neutropenia (one patient), grade 3 diarrhea with associated grade 3 hypokalemia (one patient), grade 3 handfoot syndrome (one patient), grade 3 rash (one patient), and grade 3 lethargy (three patients, coinciding with disease progression in one patient). One patient experienced no grade 3/4 toxicities. |
| Conclusions: | The recommended dose for EOC + P is epirubicin 50 mg/m(2), oxaliplatin 100 mg/m(2), capecitabine 1,000 mg/m(2)d, and P 9 mgkg every 3 weeks. This dose has been selected for the ongoingphase IIIII REAL3 study. |