Induction Lorlatinib in Stage III Non-small Cell Lung Cancer
- Registration Number
- NCT05740943
- Lead Sponsor
- Guangdong Provincial People's Hospital
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 48
- Age :18 Years to 75 Years;
- ECOG physical score 0-2 points; expected survival time ≥ 1 year;
- Pathologically confirmed diagnosis with Stage III NSCLC which harbored ALK fusion detected by next generation sequencing (NGS) or immunohistochemistry (IHC) with or without FISH. Suspected N2 (station 2/4/7) for stage III disease should be confirmed by either mediastinoscopy or EBUS.
- At least one measurable target lesion according to the RECIST 1.1 standard;
- The main organ function meets the following criteria: 1) blood routine: absolute value of neutrophils ≥ 1.5 × 109 / L, platelets ≥ 75 × 109 / L, hemoglobin ≥ 80 g / L; 2) blood biochemistry: total bilirubin ≤ 1.5 times the upper limit of normal value, aspartate aminotransferase and alanine aminotransferase ≤ 2.5 times the upper limit of normal value (if liver metastasis, ≤ upper limit of normal value 5 times), serum creatinine ≤ 1.5 times the upper limit of normal;
- Subjects voluntarily joined the study and signed informed consent, with good compliance to follow-up.
- Stage I, stage II and metastatic stage IV NSCLC;
- Histologically confirmed small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
- Patients who have previously used any other anti-tumor drugs or received surgery/radiotherapy;
- Patients with any underlying disease that investigators consider it may affect patient's prognosis including sever cardiovascular, pulmonary disease or serious infections.
- Clinically obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or patients with total gastrectomy;
- Pregnant or lactating women; those who have fertility are unwilling or unable to take effective contraceptive measures;
- Patients with low compliance or willingness to take the drugs and surveillance.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Arm Lorlatinib Patients will receive 12-week induction Lorlatinib followed by radical surgery or local radiotherapy or continue Lorlatinib through MDT and optional consolidation lorlatinib for up to 2 years.
- Primary Outcome Measures
Name Time Method Pathological Complete Response (pCR) After surgery (approximately 2 weeks) 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.
- Secondary Outcome Measures
Name Time Method Event-free Survival (EFS) From date of radical surgery till the date of first documented disease relapse, assessed up to 48 months The period after radical surgery till the time of disease relapse with either local recurrence or distant metastasis.
Dynamic ctDNA alteration From induction treatment till completion of consolidation lorlatinib (approximately 2.5 years) 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.
Overall Survival (OS) From date of induction treatment till the date of death from any cause, assessed up to 60 months. OS was assessed from initiation of treatment to death as a result of any cause.
Adverse Events (AEs) From Initiation of induction treatment till treatment discontinuation, assessed up to 24 months. Incidence of AE/SAE which has been confirmed correlation with Lorlatinib or local treatment.
Progression-free Survival (PFS) From date of induction treatment till the date of first documented disease progression or death, whichever came first, assessed up to 48 months The period after initiation of induction treatment till the time of disease progress or any cause of death.
Objective Response Rate (ORR) After last dose of induction treatment (approximately 1 week) 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.
Trial Locations
- Locations (1)
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, Guangdong, China