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

Официальное название

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)

Обзор

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.

Вмешательства

• Биопрепарат Blood samples for Hematology
  Complete blood count will include erythrocytes, neutrophils, eosinophils, basophils, lymphocytes, monocytes, platelets, leukocytes, hemoglobin, hematocrit.
• Биопрепарат Blood samples for Chemistry
  Clinical chemistry will include serum electrolytes (sodium, potassium, calcium, corrected calcium for hypoalbuminemia), creatinine, CrCl with local formula, and fasting blood glucose.
• Биопрепарат Blood sample for liver function tests
  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.
• Биопрепарат Pregnancy test
  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 tes
• Процедура Tumour assessment
  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.
• Процедура Local Ablative Therapy (LAT)
  Local Ablative Treatment (LAT) (stereotactic body radiotherapy, surgery, thermal ablation)

Первичные конечные точки

• Progression free survival (PFS) centrally assessed [Срок оценки: From the start date of treatment up to the disease progression as per central reading or for a maximum of 3 years.]

Вторичные конечные точки (5)

• Progression free survival (PFS) locally assessed [Срок оценки: 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) [Срок оценки: From the start of treatment until death or lost of follow-up or for a maximum of 3 years]
• Median PFS [Срок оценки: From the start of treatment until death or lost of follow-up or for a maximum of 3 years]
• Safety and tolerability [Срок оценки: 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) [Срок оценки: From the start date of treatment up to stop date of treatment or for a maximum of 3 years]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 27 центров

• CHU de Brest — Brest
• Centre François Baclesse — Caen
• CH Métropole-Savoie — Chambéry
• Hôpital Louis Pasteur — Colmar
• Pneumologie Centre Hospitalier Intercommunal de Créteil — Créteil
• Centre Georges-François Leclerc — Dijon
• CH Annecy — Épagny
• Polyclinique de Blois — La Chaussée-Saint-Victor
• … и ещё 19 центров

Идентификаторы

NCT: NCT06620835 · Optalk GFPC 07-2023 · 2024-A00356-41

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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