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

NCT06620835 | Recruiting Phase 2

• 2 other identifiers: Optalk GFPC 07-20232024-A00356-41
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 27

Brief 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.

Conditions

NSCLC

Keywords

NSCLC; Lung cancer; ALK rearrangement; gene mutation

Outcome Measures

Primary Outcomes (1)

• 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.

  From the start date of treatment up to the disease progression as per central reading or for a maximum of 3 years.

Secondary Outcomes (5)

• Progression free survival (PFS) locally assessed

  From the start date of treatment up to the disease progression as per local reading or for a maximum of 3 years.

• Overall survival (OS)

  From the start of treatment until death or lost of follow-up or for a maximum of 3 years

• Median PFS

  From the start of treatment until death or lost of follow-up or for a maximum of 3 years

• Safety and tolerability

  From the enrolment of the participant up to until 90 days after the last administration of radiotherapy or until 60 days after the last surgery / thermal ablation

• Duration of Treatment (DOR)

  From the start date of treatment up to stop date of treatment or for a maximum of 3 years

Study Arms (1)

Clinical Trial population

EXPERIMENTAL

All advanced non-small cell lung cancer (NSCLC) patients 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. Eligible patients will benefit from local ablative therapy with continuation of brigatinib.

Biological: Blood samples for Hematology; Biological: Blood samples for Chemistry; Biological: Blood sample for liver function tests; Biological: Pregnancy test; Procedure: Tumour assessment; Procedure: Local Ablative Therapy (LAT)

Interventions

Blood samples for Hematology BIOLOGICAL

Complete blood count will include erythrocytes, neutrophils, eosinophils, basophils, lymphocytes, monocytes, platelets, leukocytes, hemoglobin, hematocrit.

Clinical Trial population

Blood samples for Chemistry BIOLOGICAL

Clinical chemistry will include serum electrolytes (sodium, potassium, calcium, corrected calcium for hypoalbuminemia), creatinine, CrCl with local formula, and fasting blood glucose.

Clinical Trial population

Blood sample for liver function tests BIOLOGICAL

Laboratory tests to assess liver function will include Aminotransferase Alanine (ALAT), Aminotransferase Aspartate (ASAT), Phosphatase Alkaline (ALP), Gamma-glutamyl Transferase (GGT), total and conjugated bilirubin.

Clinical Trial population

Pregnancy test BIOLOGICAL

Pregnancy 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.

Clinical Trial population

Tumour assessment PROCEDURE

Tumor 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.

Clinical Trial population

Local Ablative Therapy (LAT) PROCEDURE

Local Ablative Treatment (LAT) (stereotactic body radiotherapy, surgery, thermal ablation)

Clinical Trial population

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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 \<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

You may not qualify if:

• 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 \<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.
• 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

Sponsors & Collaborators

• Groupe Francais De Pneumo-Cancerologie: lead

Study Sites (27)

CHU de Brest

Brest, 29200, France

NOT YET RECRUITING

Centre François Baclesse

Caen, 14000, France

NOT YET RECRUITING

CH Métropole-Savoie

Chambéry, 73000, France

NOT YET RECRUITING

Hôpital Louis Pasteur

Colmar, 68000, France

NOT YET RECRUITING

Pneumologie Centre Hospitalier Intercommunal de Créteil

Créteil, 94010, France

NOT YET RECRUITING

Centre Georges-François Leclerc

Dijon, 21079, France

NOT YET RECRUITING

CH Annecy

Épagny, 74370, France

NOT YET RECRUITING

Polyclinique de Blois

La Chaussée-Saint-Victor, 41260, France

NOT YET RECRUITING

CHD les Oudaries

La Roche-sur-Yon, 85000, France

NOT YET RECRUITING

CHU Dupuytren

Limoges, 87042, France

NOT YET RECRUITING

Centre Leon Bérard

Lyon, 69373, France

WITHDRAWN

Hôpital Nord

Marseille, 13915, France

NOT YET RECRUITING

CHRU de Nancy

Nancy, 54000, France

RECRUITING

CLCC Antoine Lacassagne

Nice, 06189, France

RECRUITING

CHU de Nîmes

Nîmes, 30029, France

NOT YET RECRUITING

CHU Orléans

Orléans, 45067, France

NOT YET RECRUITING

Hôpital Tenon

Paris, 75020, France

RECRUITING

CHU de Bordeaux Haut Lévêque

Pessac, 33800, France

WITHDRAWN

CHU Rennes, Hôpital Pontchaillou

Rennes, 35000, France

NOT YET RECRUITING

CHU Ponchailloux

Rennes, 35033, France

NOT YET RECRUITING

Hôpital Charles Nicolle

Rouen, 76031, France

NOT YET RECRUITING

Pneumologie CHU St Etienne

Saint-Etienne, 42270, France

NOT YET RECRUITING

CHU de la Réunion

Saint-Pierre, 97410, France

NOT YET RECRUITING

Centre Paul Strauss

Strasbourg, 67065, France

NOT YET RECRUITING

HIA St Anne

Toulon, 83800, France

NOT YET RECRUITING

CH Bretagne Atlantique

Vannes, 56017, France

NOT YET RECRUITING

Centre Hospitalier de Villefranche sur Saone

Villefranche-sur-Saône, 69655, France

NOT YET RECRUITING

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Blood Specimen Collection; Hematologic Tests; Pregnancy Tests

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Diagnostic Techniques, Obstetrical and Gynecological

Study Officials

• Jean-Bernard AULIAC

  Centre Hospitalier Intercommunal de Créteil Service Pneumologie

  PRINCIPAL INVESTIGATOR

• Isabelle MARTEL LAFAY

  Centre Léon Bérard Service Radiothérapie

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hubert CURCIO

CONTACT

+330231455160; h.curcio@baclesse.unicancer.fr

Soizic FERLANDIN

CONTACT

+330663224789; soizic_ferlandin@yahoo.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2024
• First Posted: October 1, 2024
• Study Start: June 19, 2025
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

FR (27)