A prospective, single-arm, open-label phase 2 study that evaluates the efficacy and safety of induction Lorlatinib in stage III non-small cell lung cancer and explores the clinical feasibility of dynamic ctDNA and multidisciplinary assessment in guiding local treatments.
Simon two-stage was applied to estimate the required sample size for the study. Overall an estimated 43 patients were required and at least 12 patients achieved pathological complete response would be deemed as positive result. Patients will be provided 3 cycles induction Lorlatinib 100mg and then assessed whether patients would be eligible for radical surgery or local radiotherapy through multidisciplinary evaluation. After local intervention, patients could choose consolidation treatment of Lorlatinib for up to 2 years or adjuvant doublet chemotherapy for up to 4 cycles. Dynamic blood samples will be collected before and after induction Lorlatinib as well as consolidation treatment. The primary endpoints is pCR for patients who received radical surgery.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
Patients were assigned to receive oral lorlatinib at a dose of 100 mg daily in a course of treatment that was measured in cycles of 28 days. 3 cycles of induction treatment will be required for the study.
Peking Union Medical College Hospital
Beijin, Beijin, China
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, China
Guangzhou Twelfth People's Hospital
Guangzhou, Guangdong, China
The Second Xiangya Hospital of Central South University
Changsha, Hunan, China
Pathological Complete Response (pCR)
The pathological complete response is defined as the absence of residual tumor in both lung and regional lymph nodes after induction treatment and radical surgery.
Time frame: After surgery (approximately 2 weeks)
Progression-free Survival (PFS)
The period after initiation of induction treatment till the time of disease progress or any cause of death.
Time frame: From date of induction treatment till the date of first documented disease progression or death, whichever came first, assessed up to 48 months
Objective Response Rate (ORR)
ORR is the number of participants with a Complete Response (CR) and Partial Response (PR) divided by the total number of enrolled participants per arm, then multiplied by 100. Response is based on the Response Evaluation Criteria In Solid Tumors (RECIST 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target lesions. Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions compared to baseline or the complete disappearance of target lesions, with persistence of 1 or more nontarget lesion(s) and no new lesions.
Time frame: After last dose of induction treatment (approximately 1 week)
Event-free Survival (EFS)
The period after radical surgery till the time of disease relapse with either local recurrence or distant metastasis.
Time frame: From date of radical surgery till the date of first documented disease relapse, assessed up to 48 months
Dynamic ctDNA alteration
The exploratory ctDNA alteration will be stratified into three parts. 1) Induction period: overall ctDNA clearance rate (before and after induction treatment); 2) Posttreatment period: ctDNA clearance rate after local treatment; 3) Consolidation period: 1-year and 2-year ctDNA positive rate during consolidation treatment.
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Time frame: From induction treatment till completion of consolidation lorlatinib (approximately 2.5 years)
Overall Survival (OS)
OS was assessed from initiation of treatment to death as a result of any cause.
Time frame: From date of induction treatment till the date of death from any cause, assessed up to 60 months.
Adverse Events (AEs)
Incidence of AE/SAE which has been confirmed correlation with Lorlatinib or local treatment.
Time frame: From Initiation of induction treatment till treatment discontinuation, assessed up to 24 months.