Disease	Lung cancer – NSCLC
Disease	Advanced cancer
Stage of Disease/Treatment	Metastatic/advanced
Prior Therapy	None
Type of Study – 1	Phase II
Type of Study – 2	Single arm
Primary Endpoint	Progression‐free survival
Secondary Endpoint	Overall response rate
Secondary Endpoint	Overall survival
Secondary Endpoint	Safety
Secondary Endpoint	2‐year OS rate
Additional Details of Endpoints or Study Design
Study Design and Patients
We designed a multicenter, open‐label, single‐arm, prospective, combined phase I dose‐escalation and phase II study, which was conducted as previously described 7. Eligible patients had histologically or cytologically documented unresectable locally advanced (stage III) NSCLC according to the 7th edition of the American Joint Committee on Cancer staging system. They also had to have no prior history of chemotherapy, radiotherapy, or surgery and to be able to undergo radiotherapy according to the study protocol (percentage of normal lung receiving at least 20 Gy [V20] of ≤35%). Other eligibility requirements included an age of 20–74 years, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate lung, bone marrow, liver, and kidney function. The study protocol was approved by the institutional review boards at the participating centers, and the study was conducted in accordance with the provisions of the Declaration of Helsinki. All patients provided written informed consent before enrollment. The trial has been registered in the University Hospital Medical Information Network (UMIN) database with the ID UMIN000012719. All data for the phase II study were centrally monitored by the Clinical Research Support Center Kyushu.
All patients were to be treated with nab‐P/C weekly for 6 weeks in the concurrent chemoradiation phase. Carboplatin was administered at a fixed dose of an AUC of 2 mg/ml/min during a 60‐minute intravenous (IV) infusion on day 1, and nab‐paclitaxel was administered at a dose of 50 mg/m2 during a 30‐minute IV infusion on day 1 and was repeated weekly for 6 weeks. The RD of nab‐paclitaxel during concurrent radiotherapy was determined in the phase I part of the study 7. Radiotherapy was delivered with the photon beam of a linear accelerator at 6–10 MV from day 1. The primary tumor and involved nodal disease received 60 Gy in 2‐Gy fractions over 6 weeks. A more detailed description of the radiation regimen was provided previously 7. At 4–8 weeks after the completion of concurrent radiotherapy, two 3‐week cycles of nab‐paclitaxel (100 mg/m2 on days 1, 8, and 15) plus carboplatin (AUC of 6 mg/ml/min on day 1) were administered as consolidation chemotherapy.
Details regarding baseline evaluations, toxicity assessment, and follow‐up were provided in our previous report 7. Toxicity was assessed on the basis of Common Terminology Criteria for Adverse Events version 4.0. Late toxicities were defined as adverse events occurring more than 30 days after the completion of radiotherapy. Patient response was evaluated according to RECIST version 1.1.
Statistical Analysis
The primary endpoint of the phase II part of the study was PFS. The sample size for this part of the study was calculated on the basis of an assumed PFS of 13 months, with 9 months being the lower limit of interest. Given this assumption, a sample size of 50 patients was required to achieve a power of 80% at a one‐sided level of alpha error of 0.20 according to the method of Brookmeyer and Crowley. On the basis of the additional assumption that 10% of patients would not be evaluable for response, we set the accrual goal at 56 patients for the phase II part of the study, including the 6 patients who received treatment at the RD in the phase I part. OS and PFS were estimated with the Kaplan‐Meier method.
Investigator's Analysis	Active and should be pursued further