Entry Detail
| General information | |
| Database: | DB00459 |
| Objective: | They evaluated the efficacy of sorafenib, a broad spectrum tyrosine kinase inhibitor targeting VEGFR2 and PDGFR as well as RET and RAF1, in patients with metastatic chemotherapy refractory esophageal and GE junction cancer. |
| Authors: | Janjigian YY, et al |
| Title: | Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer. |
| Journal: | PLoS One. |
| Year: | 2015 |
| PMID: | 26275293 |
| Trial Design | |
| Clinical Trial Id: | NCT00917462 |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | esophagusgastroesophageal junction cancer |
| Cancer Subtype: | advanced esophageal, gastroesophageal (GE) junction adenocarcinoma or squamous cell carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a single institution, openlabel, nonrandomized, singlearmphase II study |
| Key Patients Feature: | Eligible patients were at least 18 years old and had a diagnosis of Stage IV esophageal, gastroesophageal (GE) junction adenocarcinoma or squamous cell carcinoma with measurablelesions showing radiographic progressive disease on 2 prior chemotherapy regimens in themetastatic setting (or 3 prior regimens including perioperative chemotherapy or chemoradiotherapy). Other eligibility criteria included Karnofsky Performance Status (PS) of at least 60(requires occasional assistance, but is able to care for most of personal needs) and adequateorgan function. |
| Biomarker: | ARID1A, PIK3CA, and TP53, and focal amplifications of HMGA2 and MET |
| Biomark Analysis: | Whole exome sequencing of this tumor revealed mutations in many cancerassociated genes including ARID1A, PIK3CA, and TP53, and focal amplifications of HMGA2 and MET. |
| Control Group Info: | single arm |
| Treatment Info: | sorafenib 400 mg twice daily enrolled chemotherapy refractory patients with metastatic esophageal and GE junction cancer |
| Primary End Point: | progression free survival (PFS) rate at two months. |
| Secondary End Point: | overall survival, objective response rate and toxicity |
| Patients Number: | 34 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | Of the 34 patient evaluable for response, one (3%, 95%CI from 0% to 15%) patient with biopsy proven distant recurrence of esophageal adenocarcinoma in the neck lymph nodes within 9 weeks after combination of carboplatin and irinotecan with radiation therapy and surgery has a complete response ongoing for 5 years. Twenty of 34 patients were progression free at 2 months. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.6 months (95% CI 1.8 to 3.9 months) |
| Median OS A vs. C: | 9.7 months (95% CI 5.9 to 11.6 months) |
| Adverse Event(agent arm): | Grade 3 toxicities were uncommon and included hand foot skin reaction, rash, dehydration and fatigue. |
| Conclusions: | Sorafenib therapy results in disease stabilization and encouraging PFS in patients with refractory esophageal and GE junction cancer. |