New studies available with immunotherapy so recruitment is no longer acceptable.

Concurrent chemoradiotherapy is the standard treatment for locally advanced non-small cell lung carcinoma (NSCLC). Different chemotherapy and radiation regimens have been advocated but in general, cisplatin-doublets are deemed standard of care. Decreasing the overall treatment time of irradiation by hypofractionation is thought to increase the efficacy. Extensive experience is available on the combination of daily-dose cisplatin in combination with hypofractionated radiotherapy. However, no data is available on the safety of cisplatin doublets and hypofractionated radiotherapy

Patients presenting with locally advanced NSCLC will be consented to participate in this phase 2 trial that evaluates the concurrent treatment of cisplatin (Day 1: 75mg/m2) and pemetrexed (Day 1: 500mg/m2 for non-squamous cell lung cancer) or etoposide (Day1-3 100mg/m2 for squamous cell lung cancer), 3-weekly regimens, together with radiotherapy (24 daily fractions of 2.42 Gy to the mediastinal lymph nodes with an integrated boost of 2.75 Gy to the primary tumour). An interim analysis is planned following the first cohort of 25 patients to assess safety.

Inclusion Criteria:

• Provision of signed, written and dated informed consent prior to any study specific procedures

• Male or female aged 18 years or older

• Cytological or histological proven NSCLC stage III or inoperable stage II (cT1-3-3N0-1), according to the 8th edition of the AJCC staging.

• Patients with locoregional recurrent lung tumor following surgery or a second primary cancer are eligible, unless a pneumonectomy was performed.

• Minimum required laboratory data

• Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥1.5 x 109/L, platelets ≥ 100 x 109/L, and hemoglobin ≥ 5.5 mmol/L.

• Hepatic:

  i. Serum bilirubin ≤ 1.5 times the upper limit of normal (× ULN); alkaline phosphatase (AP), aspartate aminotransferase (ASAT), and alanine aminotransferase (ALAT) ≤ 3.0 × ULN.

ii. This does not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinaemia that is predominantly unconjugated in the absence of evidence of haemolysis or hepatic pathology) who will be allowed in consultation with their physician.

• Renal: GFR ≥ 60 ml/min; if below this threshold a creatinine clearance (CrCL) can be calculated based on the original weight based Cockcroft and Gault formula and should be ≥ 45 ml/min.

Exclusion Criteria:

• WHO performance status ≥ 2
• FEV-1 and DLCO < 35 % of the age- and gender adjusted normal value
• Patients with grade 3 dyspnea or worse at baseline (according to CTCAE version 4.03)
• Prior radiotherapy to the thorax.
• Mean lung dose > 20.0 Gy and/or exceeding other organs-at-risk constraints (page 21).
• Participation in another clinical study with an investigational product during the last 4 weeks.
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
• Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of chemotherapy.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent
• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
• Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
• Any condition that, in the opinion of the investigator, would interfere with evaluation of the chemoradiotherapy or interpretation of patient safety or study results.