LORLATINIB for Non-small cell lung cancer (ALK-positive)

Inclusion criteria

• {"criterion_text":"-Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained, and documented according to the local regulatory requirements"}
• {"criterion_text":"-Estimated life expectancy of at least 3 months irrespective of the diagnosis of ALK+ NSCLC"}
• {"criterion_text":"-For women of childbearing potential and males with partners of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 14 weeks after the last dose of study drugs"}
• {"criterion_text":"-Age at the time of signing the informed consent at least 18 years"}
• {"criterion_text":"-Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1"}
• {"criterion_text":"-Histologically or cytologically confirmed diagnosis of stage IV ALK positive NSCLC. ALK positivity can be determined by fluorescence in situ hybridization assay (FISH), immunohistochemistry (IHC) or DNA-based next-generation sequencing (NGS)"}
• {"criterion_text":"-Patients must have measurable disease according to RECIST 1.1 by computed tomography (CT) and magnetic resonance imaging (MRI)"}
• {"criterion_text":"-patients must be in progression extracranially on Lorlatinib; Lorlatinib may be in first- or further-line, without limitations regarding previously received therapies. If a patient has already received platinum (e.g. in adjuvant setting), the eligibility for PT-pem chemotherapy treatment is at the Investigator discretion"}
• {"criterion_text":"-Radiologically confirmed multiple extracranial progression on Lorlatinib without progression in the central nervous system (CNS) defined as: •\tAbsence of CNS metastasis •\tCNS metastasis stable on Lorlatinib and/or stereotactic brain irradiation (SBRT) •\tPrior radiotherapy must have been completed within 4 weeks of study entry; SBRT must have been completed at least 4 weeks before study entry; and whole-brain radiotherapy at least 4 weeks before study entry. •\tPatients with previously treated brain metastases are eligible provided they have been clinically stable for at least 4 weeks with no evidence of new or expanding brain metastases"}
• {"criterion_text":"-Adequate organ function (kidney, bone marrow and liver): - Hematology •\tAbsolute Neutrophil Count (ANC) ≥1.5 x 109 / L •\tPlatelets ≥100 x 109 / L •\tHemoglobin ≥10 g/dL (≥6.2 mmol/L) - Hepatic function •\tTotal bilirubin <1.25x UNL. In presence of a documented history of Gilbert syndrome the total bilirubin level must be <3.0x UNL •\tAST and ALT ≤1.5x UNL. If the liver has tumor involvement AST and ALT must be ≤5x UNL •\tAlkaline phosphatase ≤2.5x UNL - Renal Function •\t<1.25x ULN creatinine •\tCreatinine clearance ≥45 ml/min (according to Cockroft-Gault, if creatinine is above UNL)"}
• {"criterion_text":"-If feasible, fresh tissue biopsy demonstrating ALK translocation still present (obtained ≤ 3 months before study enrolment), assessed by local laboratory"}

Exclusion criteria

• {"criterion_text":"-Known hypersensitivity reaction to one of the compounds or substances used in this protocol"}
• {"criterion_text":"-Diagnosis of any secondary malignancy within the last 3 years, except for: adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, definitively treated nonmetastatic prostate cancer or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy"}
• {"criterion_text":"-Patients deemed unsuitable by the investigator for treatment of chemo-Lorlatinib combination"}
• {"criterion_text":"-Presence of toxicities contraindicating the continuation of therapy with Lorlatinib"}
• {"criterion_text":"-Concomitant use of potent CYP3A4/5 inducers"}

Primary endpoints

• {"endpoint_text":"-PFS defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first","definition_or_measurement_approach":"PFS defined as the time from randomization to the first documented disease progression or death due to any cause"}

Secondary endpoints

• {"endpoint_text":"-intracranial PFS defined as time from randomization until CNS disease progression or death from any cause","definition_or_measurement_approach":"Intracranial PFS defined as time from randomization until CNS disease progression or death from any cause"}
• {"endpoint_text":"-OS is defined as the time from randomization until death from any cause","definition_or_measurement_approach":"Overall survival defined as time from randomization until death from any cause"}
• {"endpoint_text":"-Frequency and severity of adverse events graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0","definition_or_measurement_approach":"Adverse events graded and reported using NCI CTCAE v5.0"}
• {"endpoint_text":"-Patient reported NSCLC specific QoL as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire: -\t Core 30 (QLQ-C30): Questionnaire consisting of 30 measuring subjects’ general cancer symptoms and functioning -\t13-item Lung Cancer (QLQ-LC13) module: A complementary questionnaire measuring lung cancer symptoms and side-effects from conventional chemo- and radiotherapy","definition_or_measurement_approach":"Patient-reported QoL measured by EORTC QLQ-C30 and QLQ-LC13 instruments"}

Methods

• Website advertisement (document: ALK-PPL_Recruitment advertisement for website) — recruitment via online advertisement for potential participants (Italy)
• Letter to GPs / primary care physicians (document: ALK-PPL_Lettera al MMG) — outreach to general practitioners to refer eligible patients (Italy)

Italy

Earliest CTIS Part Ii Submission Date

23-01-2024

Latest Decision Or Authorization Date

07-04-2026

Processing Time Days

805

Number Of Sites

14

Number Of Participants

45

Primary sponsor

Full Name

Centro Di Riferimento Oncologico Di Aviano

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy