Induction Lorlatinib in Stage III Non-small Cell Lung Cancer

Surgery Clinical Trial

Official title:

Induction Lorlatinib for ALK Fusion Locally Advanced Non-small Cell Lung Cancer: A Prospective, Single Arm, Open-label Phase 2 Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05740943
• Other study ID #: LORIN
• Status: Recruiting
• Phase: Phase 2
• Start date: March 15, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2023
• Source: Guangdong Provincial People's Hospital
• Contact: Wen-Zhao Zhong, MD.
• Phone: 86-13609777314
• Email: 13609777314[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Stage III NSCLC
• Surgery

Intervention

Drug:
• Lorlatinib
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.

Locations

Country	Name	City	State
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Guangdong Provincial People's Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

Chaft JE, Dagogo-Jack I, Santini FC, Eng J, Yeap BY, Izar B, Chin E, Jones DR, Kris MG, Shaw AT, Gainor JF. Clinical outcomes of patients with resected, early-stage ALK-positive lung cancer. Lung Cancer. 2018 Aug;122:67-71. doi: 10.1016/j.lungcan.2018.05.020. Epub 2018 May 22. — View Citation

Leonetti A, Minari R, Boni L, Gnetti L, Verze M, Ventura L, Musini L, Tognetto M, Tiseo M. Phase II, Open-label, Single-arm, Multicenter Study to Assess the Activity and Safety of Alectinib as Neoadjuvant Treatment in Surgically Resectable Stage III ALK-positive NSCLC: ALNEO Trial. Clin Lung Cancer. 2021 Sep;22(5):473-477. doi: 10.1016/j.cllc.2021.02.014. Epub 2021 Feb 24. — View Citation

Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, Mazieres J, Kim DW, Mok T, Polli A, Thurm H, Calella AM, Peltz G, Solomon BJ; CROWN Trial Investigators. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2020 Nov 19;383(21):2018-2029. doi: 10.1056/NEJMoa2027187. — View Citation

Zhang C, Li SL, Nie Q, Dong S, Shao Y, Yang XN, Wu YL, Yang Y, Zhong WZ. Neoadjuvant Crizotinib in Resectable Locally Advanced Non-Small Cell Lung Cancer with ALK Rearrangement. J Thorac Oncol. 2019 Apr;14(4):726-731. doi: 10.1016/j.jtho.2018.10.161. Epub 2018 Nov 5. — View Citation

Zhang C, Yan LX, Jiang BY, Wu YL, Zhong WZ. Feasibility and Safety of Neoadjuvant Alectinib in a Patient With ALK-Positive Locally Advanced NSCLC. J Thorac Oncol. 2020 Jun;15(6):e95-e99. doi: 10.1016/j.jtho.2019.12.133. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	After surgery (approximately 2 weeks)
Secondary	Progression-free Survival (PFS)	The period after initiation of induction treatment till the time of disease progress or any cause of death.	From date of induction treatment till the date of first documented disease progression or death, whichever came first, assessed up to 48 months
Secondary	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.	After last dose of induction treatment (approximately 1 week)
Secondary	Event-free Survival (EFS)	The period after radical surgery till the time of disease relapse with either local recurrence or distant metastasis.	From date of radical surgery till the date of first documented disease relapse, assessed up to 48 months
Secondary	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.	From induction treatment till completion of consolidation lorlatinib (approximately 2.5 years)
Secondary	Overall Survival (OS)	OS was assessed from initiation of treatment to death as a result of any cause.	From date of induction treatment till the date of death from any cause, assessed up to 60 months.
Secondary	Adverse Events (AEs)	Incidence of AE/SAE which has been confirmed correlation with Lorlatinib or local treatment.	From Initiation of induction treatment till treatment discontinuation, assessed up to 24 months.