trial for local ablative treatment (lat) optimization in patients with advanced non-small cells lung cancer (nsclc) presenting an anaplastic lymphoma kinase (alk) rearrangement treated by brigatinib

Conditions: NSCLC

Summary: 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.


Eligibility criteria:
inclusion criteria: * 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) * stable disease or response after initiation brigatinib treatment (at least 3 to 9 months) according to recist 1.1 * at least one site of residual site for lat (ie. participant should not have a complete response) * oligometastatic disease (five metastatic lesions or less and a maximum of two lesions per organ) de novo or induced * eligible for local ablative treatment possible (either alone or combined): surgery, minimally invasive form of surgical radiosurgery (stereotactic radio surgery (srs)) (18 to 20 gy in single fraction) or radiotherapy (sbrt) (27 to 54 gy in 3 fractions or 45 to 50 gy in 5 fractions), radiofrequency or cryotherapy (=thermoablation) * an eastern cooperative oncology group (ecog) performance status (ps) ≤2. * life expectancy above 12 weeks as assessed by treating investigator. * brain metastases at inclusion are allowed if asymptomatic * no history of other malignant tumor during the previous 5 years, except for adequately treated carcinomas (in situ cervical carcinoma, basal cell carcinoma, squamous cell skin carcinoma) and low-grade localized prostate cancer (gleason \&lt;6). * adequate organ function, as demonstrated by laboratory results prior to the first administration of study treatment: normal hepatic function (bilirubin ≤1.5 x upper limit of normal (uln), alanine aminotransferase (ala t) and aspartate aminotransferase (asat) ≤2.5 x uln or ≤5 x uln in case of liver metastases), renal function (calculated creatinine clearance (crcl, using local formula) above 45 ml/mn), normal hematological function (absolute neutrophil count ≥1.5 x 109/l and/or platelets ≥100 x 109/l, hemoglobin ≥8 g/dl), normal coagulation function (international normalized ratio (inr) or prothrombin time ≤1.5 x uln and activated partial thromboplastin time (aptt) or partial thromboplastin time (ptt) ≤1.5 x uln unless the patient is receiving anticoagulant therapy) * for patients of childbearing potential: women of childbearing potential should use effective non-hormonal contraception during treatment with brigatinib and for at least 4 months following the final dose. men with female partners of childbearing potential should use effective contraception during treatment and for at least 3 months after the last dose of brigatinib. * signed informed consent to participate in the study * affiliation with or benefit from french social security exclusion criteria: * 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 * leptomeningeal, pericardial, pleural and mesenteric lesions, lymphangitic spread (any tumoral lesions not amenable to definitive local therapy). peri tumoral lymphangitic spread around a tumor, but limited to a lobe, may be treated by surgery). * serious concurrent conditions during the previous 6 months (severe or unstable angina pectoris, coronary or peripheral artery bypass graft of \&lt;6 months, class 3 or 4 congestive heart failure, ischemic stroke, grade ≥2 peripheral neuropathy, psychiatric or neurological disorders that may interfere with the patient's understanding of the study or with his/her informed consent. * severe or non-controlled systemic diseases deemed incompatible with the protocol. * severe infections within 4 weeks prior to inclusion, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. * psychological, family, social, or geographical factors that may interfere with the monitoring of the patient as defined by the protocol. * any protected person (legal person protected by legal protection \[guardianship, tutorship\], person deprived of liberty, pregnant woman, breastfeeding woman, and minor). * patients who participated in other concomitant studies unless observational and received study therapy or used an investigational device within 4 weeks prior to start of study treatment * known allergies or adverse reactions to the study drugs * lung function not compatible with surgery or radiation

Keywords: nsclc lung cancer alk rearrangement gene mutation