Study assessment and end-points
toxicity, tumour, cardiac abnormalities, Cancer
ADVERSE EVENT, SOLID TUMOUR, OESOPHAGEAL CANCER, SECONDARY, TUMOUR, CANCER
The primary objective of Stage A1 was to determine the RP2D of berzosertib that can be administered concomitantly with palliative radiotherapy in oesophageal cancer. The primary objective of Stage A2 was to determine the RP2D of berzosertib that can be administered concomitantly with cisplatin and capecitabine chemotherapy in solid tumours. Secondary objectives for both A1 and A2 included (1) safety and toxicity profile of the combination, (2) feasibility of delivering the combination and (3) efficacy of the combination.The corresponding primary end-point was the highest treatment schedule resulting in a ≤25% dose limiting toxicity (DLT) rate for A1 and ≤30% DLT rate for A2; corresponding secondary end-points were (1) Grade ≥3 toxicity rate and time for toxicity resolution, (2) proportion of patients completing at least 75%, 90% and 100% of the planned dose of Radiotherapy (A1) and chemotherapy (A2) and (3) objective tumour response by RECIST 1.1, PFS and OS (and in-field RT control rate in A1).Treatment-related side-effects were reported as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.03. The DLT assessment window was confined to weeks 1–9 for A1 and weeks 1–4 for A2. DLT was generally defined as grade ≥3 haematological or organ toxicity or cardiac abnormalities. Detailed DLT criteria are provided in the 