NCT03456076进行中（未招募）3 期
A Phase III, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Adjuvant Alectinib Versus Adjuvant Platinum-Based Chemotherapy in Patients With Completely Resected Stage IB (Tumors Equal to or Larger Than 4cm) to Stage IIIA Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 257
- 试验地点
- 114
- 主要终点
- Disease-free Survival (DFS), as Assessed by the Investigator
研究概览
简要总结
This randomized, active-controlled, multicenter, open-label, Phase III study is designed to investigate the efficacy and safety of alectinib compared with platinum-based in the adjuvant setting. Participants in the experimental arm will receive alectinib at 600 mg orally twice daily (BID) taken with food for 24 months.
Participants in the control arm will receive one of the protocol specified platinum based chemotherapy regimens for 4 cycles. Following treatment completion, participants will be followed up for their disease until disease recurrence. At the time of disease recurrence, participants will enter a survival follow-up until death, withdrawal of consent or study closure, whichever occurs earlier.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years
- •Complete resection of histologically confirmed Stage IB (tumor ≥ 4 cm) to Stage IIIA (T2-3 N0, T1-3 N1, T1-3 N2, T4 N0-1) NSCLC as per Union Internationale Contre le Cancer / American Joint Committee on Cancer, 7th edition, with negative margins, at 4-12 weeks before enrollment
- •If mediastinoscopy was not performed preoperatively, it is expected that, at a minimum, mediastinal lymph node systematic sampling will have occurred
- •Documented ALK-positive disease according to an FDA-approved and CE-marked test
- •Eligible to receive a platinum-based chemotherapy regimen according to the local labels or guidelines
- •Eastern Cooperative Oncology Group Performance Status of Grade 0 or 1
- •Adequate hematologic and renal function
- •For women of childbearing potential: agreement to remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for at least 90 days after the last dose of alectinib or according to local labels or guidelines for chemotherapy
- •For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm for at least 90 days after the last dose of alectinib or according to local labels or guidelines for chemotherapy. Men must refrain from donating sperm during this same period
- •Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
排除标准
- •Pregnant or breastfeeding, or intending to become pregnant during the study or within 90 days after the last dose of alectinib or according to local labels or guidelines for chemotherapy
- •Prior adjuvant radiotherapy for NSCLC
- •Prior exposure to systemic anti-cancer therapy and ALK inhibitors
- •Stage IIIA N2 patients that, in the investigator's opinion, should receive post-operative radiotherapy treatment are excluded from the study
- •Known sensitivity to any component of study drug to which the patient may be randomized. This includes, but is not limited to, patients with galactose intolerance, a congenital lactase deficiency or glucose-galactose malabsorption.
- •Malignancies other than NSCLC within 5 years prior to enrollment, except for curatively treated basal cell carcinoma of the skin, early gastrointestinal (GI) cancer by endoscopic resection, in situ carcinoma of the cervix, ductal carcinoma in situ, papillary thyroid cancer, or any cured cancer that is considered to have no impact on disease free survival or overall survival for the current NSCLC
- •Any GI disorder that may affect absorption of oral medications, such as malabsorption syndrome or status post-major bowel resection
- •Liver disease characterized by aspartate transaminase and alanine transaminase >= 3 × upper limit of normal or impaired excretory function or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, or bleeding from esophageal varices or active viral or active autoimmune, alcoholic, or other types of acute hepatitis
- •Japanese patients participating in the serial/intensive PK sample collection only: administration of strong/potent CYP450 3A inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment with alectinib up to Week 3
- •Any exclusion criteria based on the local labels or guidelines for chemotherapy regimen
- •Patients with symptomatic bradycardia
- •History of organ transplant
- •Known HIV positivity or AIDS-related illness
- •Any clinically significant concomitant disease or condition that could interfere with-or for which the treatment might interfere with the conduct of the study or the absorption of oral medications or that would pose an unacceptable risk to the patients in this study, in the opinion of the Principal Investigator
- •Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry
研究组 & 干预措施
Alectinib
Experimental
干预措施: Alectnib (Drug)
Platinum-Based Chemotherapy
Active Comparator
干预措施: Gemcitabine (Drug)
Platinum-Based Chemotherapy
Active Comparator
干预措施: Pemetrexed (Drug)
Platinum-Based Chemotherapy
Active Comparator
干预措施: Cisplatin (Drug)
Platinum-Based Chemotherapy
Active Comparator
干预措施: Vinorelbine (Drug)
Platinum-Based Chemotherapy
Active Comparator
干预措施: Carboplatin (Drug)
结局指标
主要结局
Disease-free Survival (DFS), as Assessed by the Investigator
时间窗: Approximately 58 months
DFS, defined as the time from randomization to the first documented recurrence of disease or new primary NSCLC as determined by the investigator through use of an integrated assessment of radiographic data, biopsy sample results (if clinically feasible), and clinical status or death from any cause, whichever occurs first
Disease-free Survival (DFS), as Assessed by the Investigator
时间窗: Approximately 58 months
DFS, defined as the time from randomization to the first documented recurrence of disease or new primary NSCLC as determined by the investigator through use of an integrated assessment of radiographic data, biopsy sample results (if clinically feasible), and clinical status or death from any cause, whichever occurs first
次要结局
- Overall Survival (OS)(From the date of randomization until death due to any cause up to approximately 8 years)
- Percentage of Participants With Adverse Events (AEs)(Until 28 days after the last dose of alectinib (up to 2 years) or 28 days after end of last cycle of chemotherapy (up to 4 cycles))
- AEs Grade 3-5 With a Difference in Incidence Rate of at Least 2% Between Treatment Arms(Until 28 days after the last dose of alectinib (up to 2 years) or 28 days after end of last cycle of chemotherapy (up to 4 cycles))
- Plasma Concentration of Alectinib(Predose (2 hours) Week 3 - Week 96)
- Plasma Concentration of Alectinib Metabolite M4(Predose (2 hours) Week 3 - Week 96)
- Overall Survival (OS)(From the date of randomization until death due to any cause up to approximately 8 years)
- Percentage of Participants With Adverse Events (AEs)(Until 28 days after the last dose of alectinib (up to 2 years) or 28 days after end of last cycle of chemotherapy (up to 4 cycles))
- AEs Grade 3-5 With a Difference in Incidence Rate of at Least 2% Between Treatment Arms(Until 28 days after the last dose of alectinib (up to 2 years) or 28 days after end of last cycle of chemotherapy (up to 4 cycles))
- Plasma Concentration of Alectinib(Predose (2 hours) Week 3 - Week 96)
- Plasma Concentration of Alectinib Metabolite M4(Predose (2 hours) Week 3 - Week 96)
研究者
研究点 (114)
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相关资讯
Ongoing Trials Explore Novel Combinations and Adjuvant Therapies in EGFR- and ALK-Mutant NSCLC- The FLAURA2 and MARIPOSA phase 3 trials are evaluating the efficacy of osimertinib plus chemotherapy and lazertinib plus amivantamab, respectively, in metastatic EGFR-mutant NSCLC.
- Lorlatinib may challenge alectinib as the preferred first-line treatment for ALK-positive NSCLC due to its longer progression-free survival.
- Targeted therapies like alectinib are being investigated in earlier-stage, resected ALK-positive NSCLC, as shown in the phase 3 ALINA trial, to improve long-term survival.
- Head-to-head data release between lazertinib and osimertinib is highly anticipated from the MARIPOSA trial.last yearAdjuvant Alectinib Confirmed as New Standard of Care in ALK+ NSCLC with Favorable Safety Profile- Updated safety data from the ALINA trial reinforce adjuvant alectinib's role as a standard treatment for ALK-positive non-small cell lung cancer (NSCLC).
- Alectinib demonstrated a manageable safety profile, with most adverse events being laboratory abnormalities and infrequently leading to treatment discontinuation.
- The ALINA trial's DFS hazard ratio of 0.24 and CNS DFS hazard ratio of 0.22 highlight alectinib's significant efficacy in the adjuvant setting.
- Alectinib, approved by the FDA in April 2024, is now a preferred adjuvant treatment option for patients with resected ALK-positive NSCLC.last year