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Front-line treatment of locally advanced pancreatic adenocarcinoma with tumour treating fields concomitant with gemcitabine and nab-paclitaxel: The phase 3 PANOVA-3 study
Background
Tumour Treating Fields (TTFields) are a novel, locoregional antimitotic treatment modality approved for glioblastoma and malignant pleural mesothelioma. Continuous, non-invasive low intensity, intermediate frequency (150–200 kHz) alternating electric fields are delivered to the tumour via arrays placed on the skin. TTFields (150 kHz), with or without chemotherapy, induced antiproliferative and anticlonogenic activity on pancreatic cancer cell lines in vitro. The phase 2 PANOVA study (NCT01971281) demonstrated that the combination of TTFields with nab-paclitaxel and gemcitabine (GnP) is well-tolerated, with promising efficacy in both metastatic and locally advanced pancreatic adenocarcinoma (LAPC). These data indicated that TTFields with GnP warrant phase 3 evaluation.
Trial design
PANOVA-3 (NCT03377491) is a prospective, randomised, phase 3 trial designed to investigate the efficacy and safety of TTFields concomitant with GnP in patients with LAPC. The planned enrolment is 556 patients. Eligibility criteria include unresectable LAPC (per National Comprehensive Cancer Network guidelines), Eastern Cooperative Oncology Group performance status of 0–2, and no prior progression or treatment. Patients will be stratified by performance status and geographical region, and randomly assigned 1:1 to TTFields plus GnP or GnP alone. Based on a recent protocol amendment, a smaller and lighter-weight (reduced from 6 to 2.7 lbs) TTFields device will be used. Standard doses of nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) will be administered on days 1, 8, and 15 of a 28-day cycle. TTFields (150 kHz) will be delivered ≥ 18 h/day until local disease progression per Response Evaluation Criteria in Solid Tumours v1.1. Follow-up will be performed every 4 weeks and a computed tomography scan of the chest and abdomen every 8 weeks. After local disease progression, patients will be followed every month until death. The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival (PFS), local PFS, objective response rate, 1-year survival rate, pain- and puncture-free survival rate, rate of resectability, quality of life, and toxicity. The sample size was estimated per log-rank test comparing time to event in patients treated with TTFields plus GnP with published clinical trial data on patients treated with GnP alone. PANOVA-3 is designed to detect a hazard ratio of 0.75 in OS. Type I error is set to 0.05 (2-sided) and power to 80%. The trial is currently recruiting at 110 sites in Australia, Austria, Belgium, Canada, China, Croatia, Czech Republic, France, Germany, Hong Kong, Hungary, Israel, Italy, Poland, Spain, Switzerland, and USA. The DMC last reviewed the trial in August 2021 and suggested that the trial continue as planned.
Clinical trial identification
NCT03377491.
Legal entity responsible for the study
Novocure Ltd.
Funding
Novocure Ltd.
Disclosures
T. Macarulla: Advisory / Consultancy: (SOBI) Swedish Orpahn Biovitrum AB, Ability Pharmaceuticals SL, Aptitude Health, AstraZeneca, Basilea Pharma, Baxter, BioLineRX Ltd, Celgene, Eisai, Ellipses, Genzyme, Got It Consulting SL, Hirslanden/GITZ, Imedex, Incyte, Ipsen Bioscience, Inc., Janssen, Lilly. Marketing Farmacéutico & Investigación Clínica, S.L, MDS, Medscape, Novocure, Paraxel, PPD Development, Polaris, QED Therapeutics, Roche Farma, Sanofi-Aventis, Servier, Scilink Comunicación Científica SC, Surface Oncology, TRANSWORLD EDITORS, SL and Zymeworks; Research grant / Funding (self): Agios, Aslan, AstraZecena, Bayer, Celgene, Genentech, Hallozyme, Immunomedics, Lilly, Merimarck, Millenim, Novartis, Pfizer, Pharmacyclics and Roche; Travel / Accommodation / Expenses: Servier, prIME, AstraZeneca, Sanofi and Incyte. All other authors have declared no conflicts of interest.
