Phase IIb randomized trial of JX-594, a targeted multimechanistic oncolytic vaccinia virus, plus best supportive care (BSC) versus BSC alone in patients with advanced hepatocellular carcinoma who have failed sorafenib treatment (TRAVERSE)
| العنوان: | Phase IIb randomized trial of JX-594, a targeted multimechanistic oncolytic vaccinia virus, plus best supportive care (BSC) versus BSC alone in patients with advanced hepatocellular carcinoma who have failed sorafenib treatment (TRAVERSE) |
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| المؤلفون: | Riccardo Lencioni, Michel Homerin, David H. Kirn, Caroline J. Breitbach, Richard H. Patt, Theresa Hickman, Jean-Marc Limacher, James M. Burke, Lara Longpre, Monika Lusky |
| المصدر: | Journal of Clinical Oncology. 30:TPS4152-TPS4152 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Oncology, Cancer Research, medicine.medical_specialty, biology, business.industry, medicine.disease, Virology, Virus, Oncolytic virus, law.invention, chemistry.chemical_compound, chemistry, Randomized controlled trial, law, Internal medicine, Hepatocellular carcinoma, Cancer cell, medicine, biology.protein, In patient, Epidermal growth factor receptor, Vaccinia, business |
| الوصف: | TPS4152 Background: JX-594 is a first-in-class targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with epidermal growth factor receptor (EGFR)/ ras pathway activation. Direct oncolysis plus GM-CSF expression stimulates tumor vascular disruption and anti-tumor immunity (Nature Rev Cancer 2009). JX-594 was well-tolerated in Phase 1 trials and was shown to replicate in metastatic tumors following intratumoral (IT) or intravenous (IV) administration (Lancet Oncol 2008 and Nature 2011). A randomized dose-finding Phase 2 trial has been completed with JX-594 in 30 patients with advanced HCC. Treatment with high-dose JX-594 was associated with prolonged survival vs low-dose JX-594 (median survival 14.1 mo vs 6.7 mo; Hazard Ratio 0.39, p=0.02) (AASLD Annual Meeting, 2011, LB1). Methods: TRAVERSE is a Phase 2b randomized, open-label, multi-center trial of JX-594 plus BSC versus BSC in patients with advanced HCC who have failed sorafenib treatment. Approximately 120 patients will be randomized 2:1 to experimental and control arm respectively. Randomization will be stratified by region (Asian vs non-Asian); sorafenib intolerant vs refractory; and presence vs absence of extra-hepatic disease. The primary objective is to determine overall survival in the 2 arms. Assuming a control median overall survival of 4.0 months and a target hazard ratio of 0.57 (corresponding to an experimental arm median survival of 7.0 months), 73 events (deaths) will provide 70% power at 1-sided alpha = 0.05 to detect a difference in overall survival between the treatment groups using a stratified logrank test. Patients randomized to JX-594 will receive a dose of 109 plaque forming units (pfu) IV on Day 1 followed by five IT treatments between Day 8 and Week 18. Main inclusion criteria are advanced HCC having failed sorafenib (intolerance or radiographic progression during or < 3 months following last sorafenib), Child-Pugh A-B7 (no ascites), acceptable hematologic function. Enrollment has begun on this study with clinical trial registry number of NCT01387555. |
| تدمد: | 1527-7755 0732-183X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::3cd3110705632bdeb4c525397ff95174 https://doi.org/10.1200/jco.2012.30.15_suppl.tps4152 |
| رقم الأكسشن: | edsair.doi...........3cd3110705632bdeb4c525397ff95174 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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