Neoplasm, Esophageal Clinical Trial
Official title:
TGF-β And PDL-1 Inhibition in Esophageal Squamous Cell Carcinoma Combined With Chemoradiation TheRapY
The outcome of irresectable oesophaguscancer is poor, despite the fact that curative treatment with definitive chemoradiation is possible. The outcome of treatment can possibly be improved by combining chemoradiation with immunotherapy such as bintrafusp alfa, a combined TGF-β and PD-L1 inhibitor. In this study investigators investigate the feasibility of combining bintrafusp alfa with definitive chemoradiation in patients with irresectable squamous cell carcinoma of the esophagus.
This is a non-randomized feasibility study in which patients with esophageal squamous cell carcinoma receive bintrafusp alfa (B), combined with paclitaxel (P), carboplatin (C), and radiation (RT). For safety reasons the first ten patients will be treated in a maximum of four selected hospitals. If no unexpected safety signals occur, the study will start in all participating centers. Paclitaxel 50 mg/m2 and Carboplatin AUC = 2 will be given by intravenous infusion on days 1, 8, 15, 22, 29, and 36. External beam radiotherapy will be delivered to a total dose of 50.4 Gy in 28 fractions of 1.8 Gy, 5 fractions per week, starting the first day of the first cycle of chemotherapy (see below for details on radiation technique). Bintrafusp alfa will be given iv every three weeks on day 1, 22, and 43 at a dose of 2400 mg. Wk 1 Wk 2 Wk 3 Wk 4 Wk 5 Wk 6 Wk 7 Day 1 Day 8 Day 15 Day 22 Day 29 Day 36 Day 43 __________________________________________________ P P P P P P C C C C C C B B B RTx5 RTx5 RTx5 RTx5 RTx5 RTx3 __________________________________________________ P = paclitaxel; C = carboplatin, B = bintrafusp alfa RT = radiotherapy Feasibility of this treatment strategy is the main focus of this study. In this study feasibility is defined as ≥80% of patients completing two cycles (of in total three) cycles of bintrafusp alpha. In the ART-DECO study, which included a similar patient population, more than 80% of patients was able to receive five cycles of carboplatin and paclitaxel (i.e. up to week 5) (personal communication dr. Hulshof). Therefore, the investigators will regard treatment with Bintrafusp alfa during chemoradiation feasible if ≥80% of patients complete two cycles of bintrafusp alfa, while with a completion rate ≤62% the treatment will be regarded unfeasible. The primary end point of this feasibility study is the percentage of patients completing bintrafusp alfa treatment. This study requires 41 subjects to decide whether the proportion completing at least two cycles of bintrafusp alfa, P, is less than or equal to 0.62 or greater than or equal to 0.80. If the number of patients completing two or more cycles of Bintrafusp alfa is 31 or more, the hypothesis that P ≤ 0.62 is rejected with a target error rate of 0.05 and an actual error rate of 0.048. If the number of patients completing two or more cycles of bintrafusp alfa is 30 or less, the hypothesis that P ≥ 0,80 is rejected with a target error rate of 0.20 and an actual error rate of 0.182. The test statistic used is the one-sided one-sample test for binomial proportion, testing against the fixed reference proportion of 0.62. Taking into account 20% drop-out, 52 patients need to be included in the study. ;
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