Induction Lorlatinib in Stage III Non-small Cell Lung Cancer
Study Details
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
Simon two-stage was applied to estimate the required sample size for the study. Overall an estimated 46 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 will receive up to 2 year-consolidation treatments of Lorlatinib. Dynamic blood samples will be collected before and after induction Lorlatinib as well as consolidation Lorlatinib. The primary endpoints are progression-free survival for ITT population and pCR for patients who received radical surgery.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Treatment Arm Patients will receive 12-week induction Lorlatinib followed by radical surgery or local radiotherapy or continue Lorlatinib through MDT and consolidation lorlatinib for up to 2 years. |
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.
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Outcome Measures
Primary Outcome Measures
- 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.
- 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 progression (defined by response evaluation criteria in solid tumor criteria) or death.
Secondary Outcome Measures
- 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.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age :18 Years to 75 Years;
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ECOG physical score 0-2 points; expected survival time ≥ 1 year;
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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.
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At least one measurable target lesion according to the RECIST 1.1 standard;
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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;
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Subjects voluntarily joined the study and signed informed consent, with good compliance to follow-up.
Exclusion Criteria:
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Stage I, stage II and metastatic stage IV NSCLC;
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Histologically confirmed small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
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Patients who have previously used any other anti-tumor drugs or received surgery/radiotherapy;
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Patients with any underlying disease that investigators consider it may affect patient's prognosis including sever cardiovascular, pulmonary disease or serious infections.
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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;
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Pregnant or lactating women; those who have fertility are unwilling or unable to take effective contraceptive measures;
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Patients with low compliance or willingness to take the drugs and surveillance.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Guangdong Provincial People's Hospital | Guangzhou | Guangdong | China | 510080 |
Sponsors and Collaborators
- Guangdong Provincial People's Hospital
Investigators
- Principal Investigator: Wen-Zhao Zhong, MD., Guangdong Provincial People's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- 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.
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