First-line Immunotherapy-based Standard of Care and Local Ablative Treatments for Oligometastatic Non-small Cell Lung Cancer Patients.

Официальное название

First-line Immunotherapy-based Standard of Care and Local Ablative Treatments for Oligometastatic Non-small Cell Lung Cancer Patients: a Randomized, Multicentre, Open-label Phase III Study

Обзор

First-line immunotherapy-based standard of care and local ablative treatments for oligometastatic non-small cell lung cancer patients: a randomized, multicentre, open-label phase III study

Вмешательства

• Лучевая терапия Radical local treatment
  RLT of all metastatic sites. The possible RLT options will be SBRT, interventional radiology and/or minimally invasive surgery. Depending on the metastatic site, access and patient condition, the best RLT should be initially discussed in a case-to-case basis at the local multidisciplinary board (MTB). The primary tumour and initially invaded lymph nodes should be treated during the maintenance phase. Curative-intent approach modalities (e.g. hypofractionated intensity-modulated thoracic radiati
• Препарат SoC-based immunotherapy (+/- chemotherapy)
  Current French SoC will be used. Main SoC-based immunotherapy includes: * Platinum-based chemotherapy combined with an anti PD-1 immunotherapy (pembrolizumab). Pemetrexed-platinum combinations may be used in non- squamous carcinoma, while paclitaxel-platinum combination is favoured in squamous carcinoma. * Anti PD-1 monotherapy if PD-L1 ≥ 50% is a possible alternative (pembrolizumab or atezolizumab or cemiplimab). Other alternatives include nivolumab-ipilimumab-chemotherapy or durvalumab-treme

Первичные конечные точки

• Overall Survival (OS). [Срок оценки: From date of randomization up to two years after the randomization of the last patient or documented death.]

Вторичные конечные точки (8)

• Progression-free survival (PFS) according to RECIST 1.1. [Срок оценки: From date of randomization up to two years after the randomization of the last patient or documented death.]
• immune Progression-free survival (iPFS) according to iRECIST. [Срок оценки: From date of randomization up to two years after the randomization of the last patient or documented death.]
• Number of side effects measured by CTCAE V.5. [Срок оценки: From date of randomization up to two years after the randomization of the last patient or documented death.]
• EORTC Quality of Life Questionnaire-C30 (EORTC QLQ-C30). [Срок оценки: From date of randomization up to 24 months after the last patient included in the study, until the date of first documented progression or date of death from any cause, whichever come first.]
• EORTC Quality of Life Questionnaire Lung Cancer-specific-13 (QLQ-LC-13). [Срок оценки: From date of randomization up to 24 months after the last patient included in the study, until the date of first documented progression or date of death from any cause, whichever come first.]
• EuroQol-5D-5L Questionnaire (EQ-5D-5L). [Срок оценки: From date of randomization up to 24 months after the last patient included in the study, until the date of first documented progression or date of death from any cause, whichever come first.]
• Clearance of circulating tumour DNA (ctDNA). [Срок оценки: At the randomization, then Week 6 and Month 4 after randomization.]
• Economic evaluation. [Срок оценки: From date of randomization up to 24 months after the last patient included in the study, until the date of first documented progression or date of death from any cause, whichever come first.]

Критерии участия

Критерии включения

• Histologically proven advanced synchronous oligometastatic stage IV NSCLC.
• NSCLC patients eligible first line immunotherapy-based SoC according to the European Marketing Authorization.
• PDL1 status available.
• Metastases eligible to RLT according to the local multidisciplinary board (MTB): ≤5cm each in CT scan, excluding primary tumour.
• Maximum 5 metastases in 3 organs (EORTC criteria), according to brain MRI and FDG-PET.
• Symptomatic lesions requiring urgent palliative radiation, is permitted prior to randomization. These treated lesions should be counted towards the total number of metastases at the time of enrolment.
• Clinically required brain metastases (BM) ablation (surgery and/or SBRT) is permitted and BM count within the total number of 5 lesions. The patient would then be randomized to treatment of their extracranial disease.
• Acceptable organ function for RLT.
• ECOG performance status (PS) 0-1.
• Measurable lesions according to RECIST V1.1 on standard imaging.
• Patient aged 18 or more.
• Woman of childbearing potential must agree to use adequate contraception (implant type, vaginal ring, contraceptive pill, contraceptive patch, Intrauterine Device (IUD), etc.) for the duration of study participation and up to 6 months after completing treatment/therapy, in addition, male partners use a condom during this same period. Male patients must agree to use condom for the duration of study participation and up to 6 months after completing treatment/therapy.
• Patients affiliated to the social security system.
• Patient should understand, sign, and date the informed consent form written in French prior to any protocol-specific procedures performed.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits, and examinations including follow-up.

Критерии исключения

• Non-squamous NSCLC with targetable tumour mutations and approved first line targeted therapy (such as EGFR, ALK and ROS1).
• Metastases not eligible to RLT: e.g. brainstem or diffuse serosal metastases (meningeal, pericardial, pleural, peritoneal, mesenteric) or that invades the gastrointestinal tract.
• Brain metastases only, without extra-cerebral metastases.
• Uncontrolled severe comorbidity, symptomatic interstitial lung disease or active infection.
• Prior therapy with T-cell costimulation or immune checkpoint-targeted agents within 1 year.
• Uncontrolled concomitant (<1-year) malignancy except adequately treated basal or squamous cell carcinoma of the skin, or in-situ carcinoma of any organ or in-situ melanoma of the skin.
• Persons deprived of liberty by judicial or administrative decision.
• Persons subject to a legal protection measure (guardianship, curatorship, safeguard of justice).
• Persons not affiliated to a social security system or equivalent.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 3 центра

• Institut de Radiothérapie du Sud de l'Oise — Creil
• Centre Sainte-Catherine — Avignon
• Gustave Roussy — Villejuif

Идентификаторы

NCT: NCT06840782 · 2023-503326-39-00 · 2023/3729

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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