PEMETREXED for Advanced non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Patient must have signed a written informed consent form prior to any study specific procedures\n- Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of study participation and up to 6 months after completing treatment/therapy\n- Patients affiliated to the social security system (or equivalent).\n- 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.\n- Histologically or cytologically confirmed advanced (stage IIIB/IIIC/IV), squamous or non-squamous NSCLC\n- NSCLC patients eligible for treatment with pembrolizumab and chemotherapy according to the European Marketing Authorization: a. squamous: in combination with carboplatin and either paclitaxel or nab-paclitaxel ; b. non squamous with no EGFR or ALK positive mutations: in combination with pemetrexed and a platinum based chemotherapy\n- Patient ≥18 years of age.\n- ECOG performance status 0 – 1\n- Life expectancy >3 months\n- Measurable lesion as assessed by RECIST version 1.1.\n- Metastases and/or primary tumour eligible for 3 dimensional conventional radiotherapy (3D-CRT) or stereotactic ablative radiotherapy (SABR) in terms of dose constraints at organ at risk (according to QUANTEC review)\n- Patients must have adequate organ function defined by the following laboratory results obtained within 14 days prior to the first study treatment: a. absolute neutrophil count of ≥1 500 /mm3, b. platelets ≥ 100 000/mm3, c. haemoglobin >9 g/dL (transfusions allowed), d. creatinine clearance >60 mL/min e. bilirubin ≤1.5 X ULN (unless Gilbert’s syndrome where 3 X ULN is permitted) f. serum ALT and AST ≤2.5 X ULN (unless documented liver metastasis where ≤5 X ULN is permitted) g. ALP ≤2.5 X ULN (unless documented bone or liver metastasis where ≤5X ULN is permitted). h. INR , PT, PTT ≤1.5 X ULN (unless the subject is receiving anticoagulant therapy)"}

Exclusion criteria

• {"criterion_text":"- Non-squamous NSCLC with targetable tumor mutations, activating EGFR mutations or ALK translocation.\n- Stage IIIB/IIIC NSCLC patient eligible to curative (thoracic radiotherapy or surgery) treatments in first line treatment.\n- Prior therapy with T-cell costimulation or checkpoint-targeted agents\n- Clinical need of radiotherapy (e.g.: whole brain irradiation, painful metastasis, bleeding, compressive metastases)\n- Irradiation within 2 months before inclusion.\n- Leptomeningeal carcinomatosis, or metastases with indistinct borders making targeting not feasible\n- Patient with evidence of active (presence of symptoms or requiring steroid treatment) central nervous system (CNS) metastases and/or carcinomatous meningitis. Patient with brain metastasis can be included if asymptomatic and not requiring steroids\n- Metastases located within 3 cm of the previously irradiated structures (EQD2doses): a. Spinal cord previously irradiated to >40 Gy; b. Brachial plexus previously irradiated to >50 Gy; c. Small intestine, large intestine, or stomach previously irradiated to >45 Gy; d. Brainstem previously irradiated to >50 Gy; e. Lung previously irradiated with prior V20Gy >30%\n- Active autoimmune disease except vitiligo, type-1 diabetes, hypothyroid stabilized with hormonal substitution, psoriasis\n- Symptomatic interstitial lung disease\n- Systemic immunosuppression or systemic immunosuppressive medicinal products within 2 weeks prior to study entry.\n- Concomitant treatment with steroids > 10 mg.\n- Prior invasive malignancy within the past 2 years (except non-melanomatous skin cancer non-invasive carcinoma in-situ of the breast, oral cavity, bladder or cervix)\n- Known Acquired Immune Deficiency Syndrome (AIDS) or severe uncontrolled co-morbidity\n- Known currently active infection including hepatitis B and hepatitis C\n- Patient who was administered a live, attenuated vaccine within 28 days prior to enrolment\n- Patient with any other disease or illness that requires hospitalisation or is incompatible with the study treatment are not eligible. Patient unable to comply with study obligations for geographic, social, or physical reasons, or who is unable to understand the purpose and procedures of the study\n- Patient who have taken any investigational medicinal product or have used an investigational device within 30 days of inclusion\n- Pregnant or breast feeding woman\n- Person deprived of their liberty or under protective custody or guardianship.\n- If pemetrexed: patient is unable or unwilling to take folic acid or vitamin B12 supplementation\n- Pre-existing peripheral neuropathy of a severity of grade ≥ 2 by NCI CTCAE v5.0.\n- Known hypersensitivity to one of the compounds or substances used in this protocol.\n- Major surgery within the 28 days before initiating study treatment"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint of this trial is overall survival (OS) defined as the time from randomization to the date of documented death from any cause or last follow-up. OS rate will be reported at 1 year.","definition_or_measurement_approach":"OS defined as the time from randomization to the date of documented death from any cause or last follow-up. OS rate will be reported at 1 year."}

Secondary endpoints

• {"endpoint_text":"- Acute/ late toxicity will be assessed according to the flowchart and graded by CTCAE v5 (toxic death and serious adverse events)","definition_or_measurement_approach":"Toxicity graded by CTCAE v5; acute/late toxicity assessed according to flowchart; includes toxic death and serious adverse events."}
• {"endpoint_text":"- Tumour response is defined as the percentage of patients with a complete response (CR) or partial response (PR), according to RECIST 1.1 and iRECIST (centralized response evaluation).","definition_or_measurement_approach":"Tumour response measured as percentage of patients with CR or PR according to RECIST 1.1 and iRECIST with centralized response evaluation."}
• {"endpoint_text":"- Overall survival (OS) is defined as the time from randomization to the date of documented death from any cause or last follow-up. OS rate will be reported at 2 years.","definition_or_measurement_approach":"OS defined as time from randomization to documented death from any cause or last follow-up; OS rate reported at 2 years."}
• {"endpoint_text":"- Progression-free survival (PFS) or iPFS [Seymour, 2017] are defined as the time from randomization until documented disease progression (PD) according to RECIST 1.1 and iRECIST (centralized response evaluation for both arms), or death, or last follow-up for patient alive whichever occurs first. PFS rate will be reported at 1 year.","definition_or_measurement_approach":"PFS/iPFS defined as time from randomization to documented disease progression per RECIST 1.1 and iRECIST (centralized) or death or last follow-up, whichever occurs first; PFS rate at 1 year."}
• {"endpoint_text":"- Cancer specific survival (CSS) is defined as the time from randomization to documented death from cancer from the treatment. CSS rate will be reported at 1 year.","definition_or_measurement_approach":"CSS defined as time from randomization to documented death from cancer due to treatment; CSS rate at 1 year."}
• {"endpoint_text":"- Local and distant controls in irradiated patients are defined as the time from randomization to the first documented loco-regional event or distant event. Control rates will be reported at 6 months and 1 year","definition_or_measurement_approach":"Local/distant control: time from randomization to first documented loco-regional or distant event; rates at 6 months and 1 year."}
• {"endpoint_text":"- Quality of life will be assessed using self-administered questionnaires (EORTC QLQ-C30) according to the flowchart.","definition_or_measurement_approach":"Quality of life measured by self-administered EORTC QLQ-C30 questionnaires per flowchart."}

France

Earliest CTIS Part Ii Submission Date

29-08-2024

Latest Decision Or Authorization Date

03-11-2025

Processing Time Days

431

Number Of Sites

37

Number Of Participants

327

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France