The goal of this clinical trial is to learn if the treatment by systemic Brigatinib (ALUNBRIG®) associated to local ablative therapy (LAT) treatment is improved if administered when the brigatinib works best in participants presenting an advanced non-small cells lung cancer with an ALK gene anomaly (this anomaly produces a defective protein that is responsible for the multiplication of cancer cells).
This clinical trial is expected to involve 45 participants in several sites in France.
Advanced non-small cell lung cancer (NSCLC) participants with ALK rearrangements treated with brigatinib in first line of non-curable setting will be screened.
If the disease assessment done between 3 to 9 months after initiation of brigatinib shows:
* a tumor response or stabilization (according to RECIST 1.1) * a disease which meets the definition of an oligometastatic disease (five metastatic lesions or less and a maximum of two lesions per organ) * all tumor targets are accessible to a local ablative therapy (confirmed by an expert panel of clinicians before inclusion): surgery, stereotactic radiosurgery (SRS). For liver, adrenal, or other metastases, percutaneous thermal ablation will be accepted.
Participants will be asked to visit the clinic:
* for eligibility criteria assessment prior to LAT * for LAT * every 8 weeks for checkups and tests the first year after LAT * and then every 12 weeks, for a maximum period of 3 years.
Eligible patients will benefit from local ablative therapy with continuation of brigatinib.
Age 18 years or older at diagnosis.
Stage 3 non eligible for chemoradiotherapy or stage 4 NSCLC, histologically or cytologically confirmed NSCLC.
Tyrosine Kinase Inhibitor (TKI) treatment naïve.
ALK rearrangements identified by a validated technique (either Immunohistochimy (IHC), fluorescence in situ hybridization (FISH) or Ribonucleic Acid (RNA)seq, in tissue or liquid biopsy)
NSCLC without known ALK rearrangements
Neuroendocrine tumor (even in case of mixed tumors).
Uncontrolled and untreated superior cava syndrome.
Unstable symptomatic brain metastases despite corticosteroid
Single group
Blood samples for Hematology
Biological/VaccineComplete blood count will include erythrocytes, neutrophils, eosinophils, basophils, lymphocytes, monocytes, platelets, leukocytes, hemoglobin, hematocrit.
Blood samples for Chemistry
Biological/VaccineClinical chemistry will include serum electrolytes (sodium, potassium, calcium, corrected calcium for hypoalbuminemia), creatinine, CrCl with local formula, and fasting blood glucose.
Blood sample for liver function tests
Biological/VaccineLaboratory tests to assess liver function will include Aminotransferase Alanine (ALAT), Aminotransferase Aspartate (ASAT), Phosphatase Alkaline (ALP), Gamma-glutamyl Transferase (GGT), total and conjugated bilirubin.
Pregnancy test
Biological/VaccinePregnancy test will be performed in women of childbearing potential, including women who have had a tubal ligation. Childbearing potential is defined as not having undergone surgical sterilization, hysterectomy, and/or bilateral oophorectomy or not being postmenopausal (≥12 months of amenorrhea). Urine pregnancy tests will be based on the measurement of β-Human Chorionic Gonadotropin (HCG). If a urine pregnancy test is positive, it must be confirmed by a serum pregnancy test. Urine pregnancy tests will be performed at screening.
Tumour assessment
Procedure/SurgeryTumor assessment according to the RECIST v1.1 include the following radiological evaluation: thoracic CT scan, brain MRI or CT scan (MRI is preferred), abdominopelvic scan, PET-CT scan mandatory and at the Investigator's discretion, if needed bone scintigraphy and chest X-ray.
Local Ablative Therapy (LAT)
Procedure/SurgeryLocal Ablative Treatment (LAT) (stereotactic body radiotherapy, surgery, thermal ablation)
Progression free survival (PFS) centrally assessed
PFS is defined as the time from Brigatinib initiation until tumor progression or death from any cause according to RECIST v1.1, evaluated by the expert panel. Radiological evaluation of the target lesions(s) will be performed at the following time points: Screening, then every 8 weeks during the first year then every 12 weeks thereafter. An expert panel of blinded clinicians will anonymously review the radiological evaluations and confirm/infirm the Investigator's assessment. Each Investigator must provide all the documents necessary to assess the various endpoints. Progression occurring before 2 years will be considered for the endpoint. Patients alive without progression will be censored at the last radiological assessment.
Progression free survival (PFS) locally assessed
PFS is defined as the time from Brigatinib initiation until tumor progression or death from any cause according to RECIST v1.1, evaluated by the investigators. Radiological evaluation of the target lesions(s) will be performed at the following time points: Screening, then every 8 weeks during the first year then every 12 weeks thereafter. If a Computed Tomography (CT) scan for tumor assessment is performed in a Positron Emission Tomography (PET) scanner or CT scanner, the CT acquisition must be consistent with the standards for a full-contrast diagnostic CT scan. Response will be assessed by the Investigator at each center using RECIST v1.1. Assessments should be performed by the same evaluator, if possible, to ensure internal consistency across visits. Progression occurring before 2 years will be considered for the endpoint. Patients alive without progression will be censored at the last radiological assessment.
Overall survival (OS)
Overall survival defined as the time from Brigatinib initiation until death or lost of follow up. Patients alive will be censored at the date of last news or data cutoff. The patient's status (dead, alive or censored) will be determined at the same time points as PFS (Screening, then every 8 weeks during the first year then every 12 weeks thereafter) in order to evaluate OS. In addition, OS will be determined during the Post-study Follow-up Period via in-person or phone contact every 3 months.
Median PFS
Median PFS defined as the time from Brigatinib initiation until death or lost of follow up. Patients alive without progressive disease will be censored at the date of last news or data cutoff.
Safety and tolerability
Safety and tolerability : proportion of patients with any adverse event (AE), serious AEs (SAEs) and all AEs of grade ≥3 according to the National Cancer Institute (NCI) Common terminology criteria for adverse events (CTCAE) v5.0 criteria. Participants will be monitored for AEs from the time the informed consent form is signed until 90 days after the last administration of radiotherapy or until 60 days after the last surgery / thermal ablation. Safety assessments may include monitoring of any or all of the following parameters: clinical symptoms, laboratory, pathological, radiological or surgical findings, results of physical examination, or results of other tests and/or procedures. Any later SAE, i.e. occurring after the end of the reporting period, which is considered to be related to the trial intervention(s) or to the research (protocol required diagnostic procedures and examinations carried out during the research) must be reported without any limitation in terms of deadline.
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