The trial is subdivided in a safety run-in phase and a randomized part with the induction phase (Radiochemotherapy ± Durvalumab and including prophylactic cranial irradiation (PCI; if clinically indicated and according to local standard)) followed by the maintenance phase. The trial starts with the safety run-in phase of 6 patients in Durvalumab group. After the completion of the first cycle of all 6 patients a safety interim analysis will be performed. Study should be discontinued if ≥ 2 out of 6 patients within safety run-in phase (first cycle):~show more than 2 AEs CTCAE grade ≥3 related to study drug Durvalumab~or develop pneumonitis (CTCAE grade ≥2)~or drop out, Otherwise, the trial can continue with randomization. Eligible patients will be randomized to Durvalumab group or standard of care group 2:1.~The safety interim analysis was performed in Q4 2021. The independent DMC has recommended the continuation of the trial.~Induction phase:~Durvalumab group: Cisplatin (75 mg/m² (BSA) D1#) and Etoposide (100 mg/m² (BSA) D1-3) once every 3 weeks for 4-6 cycles and concomitant Radiotherapy (60±6 Gy, 1.8-2 Gy/d with start at latest at beginning of cycle 3, ideally during cycle 1) and additional Durvalumab (1500 mg once every 3 weeks) for 4-6 cycles according to randomization followed by prophylactic cranial irradiation (PCI, if clinically indicated and according to local standard))~Control group: Cisplatin (75 mg/m² (BSA) D1#) and Etoposide (100 mg/m² (BSA) D1-3) once every 3 weeks for 4-6 cycles and concomitant Radiotherapy (60±6 Gy, 1.8-2 Gy/d with start at latest at beginning of cycle 3, ideally during cycle 1) followed by prophylactic cranial irradiation (PCI, if clinically indicated and according to local standard)~# Due to the toxicity of Cisplatin 75 mg/m² D1, a Cisplatin split dose with 40 mg/m² on D1 and D8 is alternatively allowed and a switch of Cisplatin to Carboplatin AUC 5 (due to new contraindication to Cisplatin) after at least 2 cycles with Cisplatin. A simultaneous administration of platinum-based chemotherapy (preferred Cisplatin) and radiotherapy for at least 2 cycles should be performed.~Maintenance phase:~In Durvalumab group patients will be treated with Durvalumab once every 4 weeks until disease progression (radiologic or clinical progression) or unacceptable toxicities, if patients show at least stable disease after induction phase. Patients with PD after induction phase will have EoT visit and will be followed up until death.~Patients in control group will have EoT visit and will receive standard of care treatment until PD and thereafter will be followed up until death.
Combination of concomitant Radio-Chemotherapy showed a significant improvement (Takada) of OS and PFS in limited disease SCLC patients. This clinical trial is a prospective, multicenter, randomized, open-label, parallel group phase II investigator initiated trial (ITT) to evaluate the efficacy and safety of Durvalumab in combination with Cisplatin/Etoposide/Radiotherapy in patients with limited disease small-cell lung cancer (SCLC).