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

This is phase I/II study to evaluate the feasibility (phase I) and progression free survival (phase II) in patients with advanced NSCLC with ALK-rearrangement receiving consolidation radiation therapy (RT) to all known macroscopic tumour lesions present after 2-3 months of treatment with alectinib and then continuing with alectinib.

Eligible patients are those with an ALK-rearranged stage III (non-surgical/non-radiochemotherapy candidates) OR stage IV NSCLC who, after a 2-3-month-induction period of alectinib show stable disease/partial response to systemic therapy. When entering the trial, all known tumour lesions are treated with SBRT/RT/SRS with concomitant alectinib followed by continuation alectinib until disease progression, unacceptable toxicity or another discontinuation criterion is met.

Inclusion criteria

• Histological or cytological confirmed NSCLC:

• Stage IV NSCLC OR
• Stage III NSCLC not suitable for surgery or radiochemotherapy OR
• Recurrent NSCLC after previous surgery (not amendable for curative multimodal therapy)
• ALK-rearrangement
• Adequate organ function to tolerate alectinib and clinical tolerance to alectinib
• Stable disease (SD) or partial response (PR) after 2-3 months induction treatment with alectinib
• Maximum 5 tumour lesions +/- thoracic lymph nodes active on an 18F-FDG-PET scan post induction treatment with alectinib
• All active tumour lesions amendable to RT under the following conditions:

• All metastases possible to treat with

• Extracranial metastases: SBRT of at least 7 Gy x 5 (corresponding to 50 Gy EQD2 using alfa/beta 10Gy)
• Intracranial metastases: SRS or f-SRS
• The 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 risk
• ECOG performance status (PS) 0-2
• FEV1 ≥1 litre (only applicable for lung targets)
• Age ≥ 20 years
• Measurable lesions according to RECIST v 1.1
• Signed written informed consent

Exclusion criteria

• Leptomeningeal carcinosis (on MRI or in cerebrospinal fluid (CSF))
• Persistent malignant pleural effusion, malignant pericardial effusion or malignant ascites after induction treatment
• PD after 2-3-month-induction treatment with alectinib
• Previous TKI, chemotherapy or immunotherapy (previous adjuvant chemotherapy for early stage NSCLC is allowed) for metastatic NSCLC
• Previous RT for NSCLC (any stage)
• Previous RT for any other cancer within the last 3 years possibly interfering with the planned RT within this study
• Life expectancy of less than 6 months
• Inability 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.