Induction Lorlatinib in Stage III Non-small Cell Lung Cancer

Trial Title: Induction Lorlatinib in Stage III Non-small Cell Lung Cancer

NCT ID: NCT05740943

Condition: Stage III NSCLC
Surgery

Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung

Conditions: Keywords:
ALK fusion
Induction Treatment
Multidisciplinary
ctDNA
Lorlatinib

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: A Simon two-stage design was applied. Primary endpoint for this study was pCR. The unacceptable response rate for pCR was less than 20% and desirable response rate was 40%. The error rate for alpha was set as 0.05 and 0.2 for beta. The Optimal assay was chosen and 43 patients were to be enrolled to meet adequate statical power. 13 patients would be enrolled in stage I and at least 3 patients achieved pCR were required to proceed stage II enrollment. Overall, if 12 patients achieved pCR, the study would be determined as positive. 10% drop-off rate should be considered and at least 48 patients should be enrolled.

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Lorlatinib
Description: 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.
Arm group label: Treatment Arm

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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - 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. Exclusion Criteria: - 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.

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: Guangdong Provincial People's Hospital

Address:
City: Guangzhou
Zip: 510080
Country: China

Status: Recruiting

Contact:
Last name: Wen-Zhao Zhong, MD.

Contact backup:
Last name: Chao Zhang, MD.

Investigator:
Last name: Wen-Zhao Zhong, MD.
Email: Principal Investigator

Investigator:
Last name: Ben-Yuan Jiang, MD.
Email: Sub-Investigator

Investigator:
Last name: Chao Zhang, MD.
Email: Sub-Investigator

Start date: March 15, 2023

Completion date: December 31, 2026

Lead sponsor:
Agency: Guangdong Provincial People's Hospital
Agency class: Other

Source: Guangdong Provincial People's Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05740943