Clinical trial NCT06840782: First-line Immunotherapy-based Standard of Care and Local Ablative Treatments for Oligometastatic Non-small Cell Lung Cancer Patients.
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Oligometastatic Non-small Cell Lung Cancer (NSCLC)
Keywords: Local ablative treatments
First-line immunotherapy
SBRT
Interventional radiology
Minimally invasive surgery
Lead sponsor: Gustave Roussy, Cancer Campus, Grand Paris
Sponsor class: OTHER
First posted: 2025-02-21
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Overall Survival (OS).
timeFrame: From date of randomization up to two years after the randomization of the last patient or documented death.
Secondary outcomes:
measure: Progression-free survival (PFS) according to RECIST 1.1.
timeFrame: From date of randomization up to two years after the randomization of the last patient or documented death.
measure: immune Progression-free survival (iPFS) according to iRECIST.
timeFrame: From date of randomization up to two years after the randomization of the last patient or documented death.
measure: Number of side effects measured by CTCAE V.5.
timeFrame: From date of randomization up to two years after the randomization of the last patient or documented death.
measure: EORTC Quality of Life Questionnaire-C30 (EORTC QLQ-C30).
timeFrame: 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.
measure: EORTC Quality of Life Questionnaire Lung Cancer-specific-13 (QLQ-LC-13).
timeFrame: 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.
measure: EuroQol-5D-5L Questionnaire (EQ-5D-5L).
timeFrame: 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.
measure: Clearance of circulating tumour DNA (ctDNA).
timeFrame: At the randomization, then Week 6 and Month 4 after randomization.
measure: Economic evaluation.
timeFrame: 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.
Other outcomes:
Locations:
city: Villejuif
country: France
facility: Gustave Roussy
Study officials:
References: