An Open-label, Single-arm, Multicenter, Prospective Study of Lorlatinib in Patients With ALK-Positive NSCLC With Brain or Leptomeningeal Metastases

Guangdong Association of Clinical Trials4 sites in 1 country41 target enrollmentAugust 1, 2024

ConditionsCarcinoma, Non-Small-Cell Lung Brain Metastases Leptomeningeal Metastasis

InterventionsLorlatinib

DrugsLorlatinib

Overview

Phase: Phase 4
Intervention: Lorlatinib
Conditions: Carcinoma, Non-Small-Cell Lung
Sponsor: Guangdong Association of Clinical Trials
Enrollment: 41
Locations: 4
Primary Endpoint: intracranial objective response rate（iORR）
Status: Active, not recruiting
Last Updated: 23 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study is an investigator-initiated, prospective, open-label, single-arm, multicenter clinical trial aimed at exploring the antitumor activity of Lorlatinib in ALK-positive NSCLC patients with brain/ leptomeningeal metastases.

Detailed Description

Fifty eligible subjects will be divided into a BM cohort (brain parenchymal metastasis only) and an LM cohort (leptomeningeal metastasis ± brain parenchymal metastasis). All subjects will receive Lorlatinib 100 mg once daily on days 1 to 28 of each 28-day cycle.

Registry

clinicaltrials.gov

Start Date

August 1, 2024

End Date

March 1, 2027

Last Updated

23 days ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Guangdong Association of Clinical Trials

Responsible Party

Principal Investigator

Jin-Ji Yang

PhD, MD

Guangdong Association of Clinical Trials

Eligibility Criteria

Inclusion Criteria

•Age ≥18 years, regardless of sex.
•Histologically or cytologically confirmed ALK-positive NSCLC.
•ALK rearrangement positive confirmed by FISH, RT-PCR, IHC Ventana D5F3, or NGS. Patients with other actionable genomic alterations in addition to ALK must be reviewed by the study expert panel to determine eligibility.
•Patients who have not received prior systemic treatment for advanced NSCLC, or who have experienced disease progression on or intolerance to at least one prior systemic treatment regimen, including an ALK inhibitor, are eligible for enrollment. If the treatment immediately prior to study drug administration was an ALK inhibitor, the washout period may be determined after discussion by the study expert panel.
•Toxicities related to prior systemic treatment must have recovered to ≤ Grade 1 (CTCAE version 5.0) or to baseline levels, except for adverse events that, in the investigator's judgment, do not pose a safety risk to the subject.
•At least one CNS lesion meeting one of the following criteria must be present: 1.leptomeningeal metastasis suggested by imaging and/or cerebrospinal fluid findings; cerebrospinal fluid confirmation is not required for imaging-suspected leptomeningeal metastasis; or 2.brain parenchymal metastasis confirmed by magnetic resonance imaging (MRI), with ≥3 brain lesions, or 1-2 lesions that are not suitable for surgery or for which the patient refuses surgery. In patients without leptomeningeal metastasis, at least one measurable brain lesion with a diameter of ≥5 mm is required.
•Patients with or without symptoms related to brain and/or leptomeningeal metastases are eligible.
•Life expectancy must be at least 12 weeks.
•ECOG performance status of 0-2 for patients without leptomeningeal metastasis, and 0-3 for patients with leptomeningeal metastasis.
•The investigator considers the subject to have generally adequate major organ function, including hematologic, coagulation, hepatic, renal, and pancreatic function.

Exclusion Criteria

•1\. Prior treatment with the investigational drug, or known hypersensitivity to the active substance or any excipients of the investigational drug.
•2\. Concurrent participation in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up phase of an interventional study. Subjects who have received any other investigational drug within 28 days before initiation of study treatment are excluded.
•In the investigator's judgment, the subject requires urgent local intervention, such as surgery or radiotherapy.
•Presence of spinal cord compression, unless pain symptoms and neurological function have remained stable or improved for at least 2 weeks prior to enrollment.
•Open surgery within 14 days prior to enrollment, except for procedures performed for biopsy purposes.
•Fever \>38°C within 1 week prior to enrollment; or clinically significant bacterial, fungal, or viral infection, including but not limited to HIV infection, active HCV infection, or active pulmonary tuberculosis; or infectious complications requiring hospitalization, bacteremia, severe pneumonia, or other clinically significant infections.
•Clinically significant abnormalities in rhythm, conduction, or morphology on resting electrocardiogram (ECG), such as complete left bundle branch block, second-degree or higher atrioventricular block, clinically significant ventricular arrhythmia, or atrial fibrillation.
•Current or recent (within 3 months prior to enrollment) unstable angina, congestive heart failure (New York Heart Association Class III or IV), myocardial infarction, coronary artery or peripheral artery bypass grafting, cerebrovascular accident, transient ischemic attack not adequately treated with anticoagulation, or symptomatic pulmonary embolism.
•Current clinically active interstitial lung disease, or radiation pneumonitis requiring corticosteroid treatment on the day of enrollment.
•Dysphagia, active gastrointestinal disease, or any other condition that may significantly affect the absorption, distribution, metabolism, or excretion of the investigational drug; or history of major gastric resection.

Arms & Interventions

BM/LM cohort

Fifty eligible subjects will be divided into a BM cohort (brain parenchymal metastasis only) and an LM cohort (leptomeningeal metastasis ± brain parenchymal metastasis)

Intervention: Lorlatinib

Outcomes

Primary Outcomes

intracranial objective response rate（iORR）

Time Frame: From date of the first dose of lorlatinib treatment until the date of last follow up or death, up to 18 months.

BM Cohort: percentage of participants demonstrating an intracranial complete response or partial response according to modified RECIST v1.1 criteria; LM Cohort: percentage of participants demonstrating an intracranial complete response or partial response according to the imaging criteria of RANO-LM.

Secondary Outcomes

Disease control rate (DCR) and intracranial disease control rate (iDCR)(From date of the first dose of lorlatinib treatment until the date of last follow up or death, up to 18 months.)
Progression-free survival (PFS) and intracranial PFS（iPFS）(From date of the first dose of lorlatinib treatment until the date of last follow up or death, up to 18 months.)
Obiective response rate (ORR)(From date of the first dose of lorlatinib treatment until the date of last follow up or death, up to 18 months.)
Overall survival(From date of the first dose of lorlatinib treatment until the date of last follow up or death, up to 18 months.)
Number of participants with adverse events(From date of the first dose of lorlatinib treatment until the date of last follow up or death, up to 18 months.)