Utilizing an interim futility analysis of the OVAL study (VB-111-701/GOG 3018) for potential reduction of risk: A phase III, double blind, randomized controlled trial of ofranergene obadenovec (VB-111) and weekly paclitaxel in patients with platinum resistant ovarian cancer
| Autor: | Angeles Alvarez Secord, Michal Lavi, Bradley J. Monk, Austin Miller, Jonathan A. Ledermann, Kathleen N. Moore, Richard T. Penson, Tamar Rachmilewitz Minei, Laurence S. Freedman, Thomas J. Herzog, Krishnansu S. Tewari, Shifra Fain Shmueli, Ronnie Shapira-Frommer, Rebecca C. Arend |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult medicine.medical_specialty Randomization Paclitaxel Placebo Drug Administration Schedule law.invention Adenoviridae 03 medical and health sciences 0302 clinical medicine Randomized controlled trial Double-Blind Method law Interim Internal medicine Medicine Humans Transgenes fas Receptor Aged Response rate (survey) Aged 80 and over Ovarian Neoplasms business.industry Surrogate endpoint Obstetrics and Gynecology Cancer Genetic Therapy Middle Aged medicine.disease Interim analysis Combined Modality Therapy 030104 developmental biology Oncology Receptors Tumor Necrosis Factor Type I 030220 oncology & carcinogenesis Angiogenesis Inducing Agents Female business |
| Zdroj: | Gynecologic oncology. 161(2) |
| ISSN: | 1095-6859 |
| Popis: | Objective Report the results from a preplanned interim analysis of a phase III, double blind, randomized controlled study of ofranergene obadenovec (VB-111), a targeted anti-cancer gene therapy, in combination with paclitaxel in patients with platinum resistant ovarian cancer (PROC). Methods The OVAL (NCT03398655) study is an on-going study where patients are randomly assigned in a 1:1 ratio to weekly paclitaxel 80 mg/m2 with VB-111 or placebo. The protocol specifies a pre-planned unblinded futility interim analysis of CA-125 response per GCIG criteria in the first 60 evaluable patients. The futility rule determined for this analysis was that the response rate of VB-111 must be greater than the response rate of placebo by at least 10% in order to continue the study. Coincident with the interim analysis, the blinded CA-125 response rate was estimated as a proportion of the first 60 evaluable patients with CA-125 response per GCIG criteria. Post-treatment fever is provided as a possible surrogate marker of VB-111 therapy activity. Results The median age of the evaluable patients was 62 years (range 41-82); 97% had high-grade serous cancer; 58% had been treated with 3 or more previous lines of therapy, 70% received prior anti-angiogenic treatment, 43% received prior PARP inhibitors. CA-125 response in the VB-111 and weekly paclitaxel treated arm met the pre-specified interim criterion of an absolute advantage of 10% or higher compared to the control. Blinded results show a 53% CA-125 response rate (32/60) with 15% complete response (n=9). Assuming balanced randomization and an absolute advantage of 10% or higher to the VB-111 arm, it may be deducted that the response in the VB-111 treatment arm is 58% or higher. Among patients with post-treatment fever, the CA-125 response rate was 69%. Conclusions At the time of the interim analysis, response rate findings are comparable to the responses seen in a similar patient population in the phase I/II study. The independent data and safety monitoring committee (iDSMC) recommended continuing the OVAL trial as planned. No new safety signals were identified. |
| Databáze: | OpenAIRE |
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