Durvalumab (MEDI4736) in Combination With Consolidative Radiochemotherapy and Ablative Stereotactic Radiotherapy in Extensive Stage SCLC
Open-label, single-arm, prospective multicenter phase II clinical trial to determine the efficacy of immunotherapy with durvalumab concomitant with radiochemotherapy, followed by durvalumab maintenance therapy in combination with stereotactic radiotherapy in extensive stage SCLC
∙ For inclusion in the study patients must fulfill all of the following criteria:
• Histologically confirmed first diagnosis of ES-SCLC according to the Veterans Administration Lung Study Group (VALG) Staging System for SCLC1 (disease extension that cannot be treated within one radiation field).
• Oligometastatic disease defined as follows:
‣ Primary tumor with or without mediastinal or supraclavicular lymph node metastases (counts as one lesion if it can be treated within one radiation field).
⁃ Up to four distant tumor lesions/metastases that can be treated with stereotactic radiotherapy (stereotactic radiotherapy of lung metastases in addition to radiochemotherapy of primary tumor should previously be discussed with the principal investigator).
⁃ No cytologically confirmed malignant pleural effusion (in case of suspected malignant pleural effusion in imaging, pleurocentesis for cytological assessment is required).
• Stable disease (SD) or partial response (PR) according to RECIST 1.1 criteria after previous treatment with two cycles of platinum/etoposide/durvalumab.
• Adequate lung function defined as forced expiratory volume in the first second (FEV1) ≥1.3 liter in spirometry.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent including European Union Data Privacy Directive obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
• Age \> 18 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Body weight \>30 kg.
• Adequate normal organ and marrow function as defined below:
‣ Hemoglobin ≥9.0 g/dL
⁃ White Blood Cells (WBC) ≥ 3,000 per mm3
⁃ Platelet count \>100,000 per mm3
⁃ Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
⁃ AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
⁃ Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula
⁃ Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow-up.
⁃ Must have a life expectancy of at least 12 weeks.