Clinical trial NCT06620835: 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
Official title: Optimization of Treatment With Brigatinib in Patients With Advanced NSCLC Harboring an ALK Rearrangement by LAT at the Time of Best Response: A Multicenter Open Phase Two Trial (OPTALK)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: NSCLC
Keywords: NSCLC
Lung cancer
ALK rearrangement
gene mutation
Lead sponsor: Groupe Francais De Pneumo-Cancerologie
Sponsor class: OTHER
First posted: 2024-10-01
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression free survival (PFS) centrally assessed
timeFrame: From the start date of treatment up to the disease progression as per central reading or for a maximum of 3 years.
Secondary outcomes:
measure: Progression free survival (PFS) locally assessed
timeFrame: From the start date of treatment up to the disease progression as per local reading or for a maximum of 3 years.
measure: Overall survival (OS)
timeFrame: From the start of treatment until death or lost of follow-up or for a maximum of 3 years
measure: Median PFS
timeFrame: From the start of treatment until death or lost of follow-up or for a maximum of 3 years
measure: Safety and tolerability
timeFrame: 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
measure: Duration of Treatment (DOR)
timeFrame: From the start date of treatment up to stop date of treatment or for a maximum of 3 years
Other outcomes:
Locations:
city: Brest
country: France
facility: CHU de Brest
city: Caen
country: France
facility: Centre François Baclesse
city: Chambery
country: France
facility: CH Métropole-Savoie
city: Colmar
country: France
facility: Hôpital Louis Pasteur
city: Creteil
country: France
facility: Pneumologie Centre Hospitalier Intercommunal de Créteil
city: La Chaussee Saint Victor
country: France
facility: Polyclinique de Blois
city: La Roche-sur-Yon
country: France
facility: CHD les Oudaries
city: Limoges
country: France
facility: CHU Dupuytren
city: Lyon
country: France
facility: Centre Leon Bérard
city: Marseille
country: France
facility: Hôpital Nord
city: Orléans
country: France
facility: CHU Orléans
city: Pessac
country: France
facility: CHU de Bordeaux Haut Lévêque
city: Rennes
country: France
facility: CHU Ponchailloux
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: Saint-etienne
country: France
facility: Pneumologie CHU St Etienne
city: Saint-pierre
country: France
facility: CHU de la Réunion
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Toulon
country: France
facility: HIA St Anne
city: Vannes
country: France
facility: CH Bretagne Atlantique
city: Villefranche Sur Saone
country: France
facility: Centre Hospitalier de Villefranche sur Saone
city: Épagny
country: France
facility: CH Annecy
Study officials:
affiliation: Centre Hospitalier Intercommunal de Créteil Service Pneumologie
name: Jean-Bernard AULIAC
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Léon Bérard Service Radiothérapie
name: Isabelle MARTEL LAFAY
role: PRINCIPAL_INVESTIGATOR
References: