A Phase I-III, Multicenter Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Patients Selected According to Biomarker Status, With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer

Hoffmann-La Roche176 个研究点分布在 10 个国家目标入组 71 人2022年11月1日

适应症Non-Small Cell Lung Cancer

干预措施Alectinib Durvalumab Entrectinib

相关药物Alectinib Entrectinib Durvalumab

概览

阶段: 3 期
干预措施: Alectinib
疾病 / 适应症: Non-Small Cell Lung Cancer
发起方: Hoffmann-La Roche
入组人数: 71
试验地点: 176
主要终点: Progression-free survival (PFS)
状态: 进行中（未招募）
最后更新: 上个月

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

This study will evaluate the efficacy and safety of multiple therapies in participants with locally advanced, unresectable, Stage III NSCLC with eligible biomarker status as determined by Version 8 of the American Joint Committee on Cancer/Union for International Cancer Control NSCLC staging system.

注册库

clinicaltrials.gov

开始日期

2022年11月1日

结束日期

2030年6月19日

最后更新

上个月

研究类型

Interventional

研究设计

Parallel

性别

All

研究者

发起方

Hoffmann-La Roche

责任方

Sponsor

入排标准

入选标准

•(All Cohorts):
•Body weight \>/= 30 kg at screening
•Willingness and ability to use the electronic device(s) or application(s) for the electronic patient-reported outcome (PRO)
•Whole-body positron emission tomography/computed tomography scan (PET/CT) (from the base of skull to mid-thighs) for the purposes of staging, performed prior and within 42 days for Cohort A2 (ROS1 positive) and 50 days for Cohort A1 (ALK positive) of the first dose of cCRT or sCRT
•Histologically or cytologically documented locally advanced, unresectable Stage III NSCLC of either squamous or non-squamous histology
•Prior receipt of at least two prior cycles of platinum-based chemotherapy given concurrently with radiotherapy (cCRT); or at least two prior cycles of platinum-based chemotherapy given prior to radiotherapy (sCRT)
•The RT component in the cCRT or sCRT must have been at a total dose of radiation of 60 (+/-10%) Gy (54 Gy to 66 Gy) administered by intensity-modulated radiotherapy (preferred) or three dimension (3D)-conforming technique
•No disease progression during or following platinum-based cCRT or sCRT
•Life expectancy \>/= 12 weeks
•Confirmed availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen

排除标准

•(All Cohorts):
•Any history of previous NSCLC and/or any history of prior treatment for NSCLC (patients must be newly diagnosed with unresectable Stage III disease)
•Any evidence of Stage IV disease, including, but not limited to, the following: pleural effusion, pericardial effusion, brain metastases, history of intracranial hemorrhage or spinal cord hemorrhage, bone metastases, distant metastases
•If a pleural effusion is present, the following criteria must be met to exclude malignant involvement (T4 disease): when pleural fluid is visible on both the CT scan and chest X-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative; participants with exudative pleural effusions are excluded regardless of cytology; participants with effusions that are minimal (i.e., not visible on chest X-ray) that are too small to safely tap are eligible
•NSCLC known to have a known or likely oncogenic-driver mutation in the EGFR gene, as identified by site local testing or Sponsor central testing
•Liver disease, characterized by any of the following: impaired excretory function (e.g., hyperbilirubinemia), synthetic function, or other conditions of decompensated liver disease, such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices or active viral or active autoimmune, alcoholic, or other types of acute hepatitis
•Positive hepatitis B surface antigen (HBsAg) test at screening
•Participants known to be positive for hepatitis C virus (HCV) antibody (Ab) are excluded with the following exception: participants who are HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution are eligible
•HIV infection: participants are excluded if not well-controlled as defined by the protocol
•Known active tuberculosis

研究组 & 干预措施

Cohort A1: ALK-Positive (alectinib arm)

Participants will receive alectinib 600 mg orally twice daily until completion of treatment period (3 years), or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first

干预措施: Alectinib

Cohort A1: ALK-positive (durvalumab arm)

Participants will receive 1500 mg of intravenous (IV) durvalumab every 4 weeks until completion of treatment period (1 year) or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first

干预措施: Durvalumab

Cohort A2: ROS 1-positive (entrectinib arm)

Participants will receive entrectinib 600 mg orally once daily until completion of treatment period (3 years), or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first. Cohort A2 has been closed to enrollment.

干预措施: Entrectinib

Cohort A2: ROS 1-positive (durvalumab arm)

Participants will receive 1500 mg of IV durvalumab every 4 weeks until completion of treatment period (1 year) or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first Cohort A2 has been closed to enrollment.

干预措施: Durvalumab

结局指标

主要结局

Progression-free survival (PFS)

时间窗: From randomization to the first documented disease progression as determined by blinded independent central review (BICR) per Response Evaluation Criterial in Solid Tumors (RECIST) v1.1, or death from any cause, whichever occurs first (up to 3 years)

次要结局

Time to central nervous system (CNS) progression(From randomization to the first occurrence of disease progression in the CNS as determined by BICR per RECIST v1.1 (up to 3 years))
Distant metastasis-free survival (DMFS)(From randomization to the first occurrence of distant metastasis or death (whichever occurs first) as determined by BICR per RECIST v1.1 (up to 3 years))
Objective response rate (ORR), defined as the percentage of participants with measurable disease who attain a complete response (CR) or partial response (PR) as determined by the investigator per RECIST v1.1(Up to 3 years)
PFS(From randomization to the first documented disease progression as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurs first (up to 3 years))
Duration of response (DOR)(From the first documented CR or PR to the first documented disease progression or death (whichever occurs first) as determined by the investigator per RECIST v1.1 (up to 3 years))
ORR, defined as the percentage of participants with measurable disease who attain a CR or PR as determined by BICR per RECIST v1.1(Up to 3 years)
DOR(From the first documented CR or PR to the first documented disease progression or death (whichever occurs first) as determined by BICR per RECIST v1.1 (up to 3 years))
Overall survival (OS)(From randomization to death from any cause (up to 5 years))
Time to CNS progression(From randomization to the first occurrence of disease progression in the CNS as determined by the investigator per RECIST v1.1 (up to 3 years))
Time-to-confirmed deterioration (TTCD)(From randomization to the first deterioration of >/= 10 points that is either maintained for two consecutive assessments or followed by death from any cause within 3 weeks (up to 3 years))
Proportion of participants who have maintained or improved baseline health as measured by the European Organisation for the Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 physical functioning and role functioning scales(5, 11, and 17 months)
Proportion of participants who have maintained or improved from their baseline health in cough, chest pain, and dyspnea symptoms as measured using the EORTC QLQ-LC13(5, 11, and 17 months)
Percentage of participants with adverse events (AEs)(Up to 3 years)