Back to resultsInduction Lorlatinib in Stage III Non-small Cell Lung Cancer
Primary Purpose
Stage III NSCLC, Surgery
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Lorlatinib
Sponsored by
About this trial
This is an interventional treatment trial for Stage III NSCLC focused on measuring ALK fusion, Induction Treatment, Multidisciplinary, ctDNA, Lorlatinib
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.
Sites / Locations
- Guangdong Provincial People's HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment Arm
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Progression-free Survival (PFS)
The period after initiation of induction treatment till the time of disease progress or any cause of death.
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.
Event-free Survival (EFS)
The period after radical surgery till the time of disease relapse with either local recurrence or distant metastasis.
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.
Overall Survival (OS)
OS was assessed from initiation of treatment to death as a result of any cause.
Adverse Events (AEs)
Incidence of AE/SAE which has been confirmed correlation with Lorlatinib or local treatment.
Full Information
NCT ID
NCT05740943
First Posted
February 12, 2023
Last Updated
May 20, 2023
Sponsor
Guangdong Provincial People's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05740943
Brief Title
Induction Lorlatinib in Stage III Non-small Cell Lung Cancer
Official Title
Induction Lorlatinib for ALK Fusion Locally Advanced Non-small Cell Lung Cancer: A Prospective, Single Arm, Open-label Phase 2 Study
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 15, 2023 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Guangdong Provincial People's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage III NSCLC, Surgery
Keywords
ALK fusion, Induction Treatment, Multidisciplinary, ctDNA, Lorlatinib
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment Arm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Lorlatinib
Intervention 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.
Primary Outcome Measure Information:
Title
Pathological Complete Response (pCR)
Description
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)
Secondary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
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
Title
Objective Response Rate (ORR)
Description
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)
Title
Event-free Survival (EFS)
Description
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
Title
Dynamic ctDNA alteration
Description
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.
Time Frame
From induction treatment till completion of consolidation lorlatinib (approximately 2.5 years)
Title
Overall Survival (OS)
Description
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.
Title
Adverse Events (AEs)
Description
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wen-Zhao Zhong, MD.
Phone
86-13609777314
Email
13609777314@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Chao Zhang, MD.
Phone
86-15920473691
Email
15920473691@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wen-Zhao Zhong, MD.
Organizational Affiliation
Guangdong Provincial People's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Guangdong Provincial People's Hospital
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wen-Zhao Zhong, MD.
First Name & Middle Initial & Last Name & Degree
Chao Zhang, MD.
First Name & Middle Initial & Last Name & Degree
Wen-Zhao Zhong, MD.
First Name & Middle Initial & Last Name & Degree
Ben-Yuan Jiang, MD.
First Name & Middle Initial & Last Name & Degree
Chao Zhang, MD.
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Partial clinicopathological data of participants will be presented in the corresponding manuscript.
Citations:
PubMed Identifier
30408570
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.
Results Reference
background
PubMed Identifier
33762169
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.
Results Reference
background
PubMed Identifier
32471573
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.
Results Reference
background
PubMed Identifier
30032847
Citation
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.
Results Reference
background
PubMed Identifier
33207094
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.
Results Reference
background
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Induction Lorlatinib in Stage III Non-small Cell Lung Cancer
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