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 (OPTALK)

Groupe Francais De Pneumo-Cancerologie

Status and phase

Not yet enrolling

Phase 2

Conditions

NSCLC

Treatments

Biological: Pregnancy test

Biological: Blood sample for liver function tests

Procedure: Tumour assessment

Biological: Blood samples for Hematology

Procedure: Local Ablative Therapy (LAT)

Biological: Blood samples for Chemistry

Study type

Interventional

Funder types

Other

Identifiers

NCT06620835

2024-A00356-41 (Other Identifier)

Optalk GFPC 07-2023

Details and patient eligibility

About

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.

Enrollment

45 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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 <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 <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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

45 participants in 1 patient group

Clinical Trial population

Experimental group

Description:

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.

Treatment:

Procedure: Local Ablative Therapy (LAT)

Biological: Blood samples for Chemistry

Biological: Blood samples for Hematology

Procedure: Tumour assessment

Biological: Blood sample for liver function tests

Biological: Pregnancy test