Alectinib Followed by Concomitant Consolidation Radiation Therapy in Advanced NSCLC With ALK-rearrangement (A-SAB)

The goal of this clinical trial is to learn evaluate the safety and efficacy of the addition of radiation therapy to all tumour lesions, to first line medical treatment with alectinib in non-small cell lung cancer harbouring ALK-rearrangements.The main aims of the trial are to evaluate:if the treatment combination is safeif the treatment combination can inhibit progressionParticipants who have responded to 1st line alectinib will be treated with consolidation radiation therapy to all remaining tumour lesions while continuing on alectinib until disease progression, unacceptable toxicity or another discontinuation criterion is met.

Inclusion Criteria:Histological or cytological confirmed NSCLC:Stage IV NSCLC ORStage III NSCLC not suitable for surgery or radiochemotherapy ORRecurrent NSCLC after previous surgery (not amendable for curative multimodal therapy)ALK-rearrangementAdequate organ function to tolerate alectinib and clinical tolerance to alectinibStable disease (SD) or partial response (PR) after 2-3 months induction treatment with alectinibMaximum 5 tumour lesions +/- thoracic lymph nodes active on an 18F-FDG-PET scan post induction treatment with alectinibAll active tumour lesions amendable to RT under the following conditions:All metastases possible to treat withExtracranial metastases: SBRT of at least 7 Gy x 5 (corresponding to 50 Gy EQD2 using alfa/beta 10Gy)Intracranial metastases: SRS or f-SRSThe primary tumour and/or lymph nodes and/or pulmonary metastases amendable to SBRT (≥ 7Gy x 5, see above) or moderately hypofractionated RT of 3 Gy x 15 (corresponding to 49 Gy EQD2 using alfa/beta 10Gy)Adequate organ function to tolerate SBRT/RT:Fulfilment of dose constraints to adequate organs at riskECOG performance status (PS) 0-2FEV1 ≥1 litre (only applicable for lung targets)Age ≥ 20 yearsMeasurable lesions according to RECIST v 1.1Signed written informed consentExclusion Criteria:Leptomeningeal carcinosis (on MRI or in cerebrospinal fluid (CSF))Persistent malignant pleural effusion, malignant pericardial effusion or malignant ascites after induction treatmentPD after 2-3-month-induction treatment with alectinibPrevious TKI, chemotherapy or immunotherapy (previous adjuvant chemotherapy for early stage NSCLC is allowed) for metastatic NSCLCPrevious RT for NSCLC (any stage)Previous RT for any other cancer within the last 3 years possibly interfering with the planned RT within this studyLife expectancy of less than 6 monthsInability to understand given information or undergo study procedures according to protocol.Has evidence or a past medical history of interstitial lung disease or active, non-infectious pneumonitis or known pulmonary fibrosis.Pregnant or breast-feeding. Patients must agree to use safe contraception during and for 3 months after study treatment.