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Report for Clinical Trial NCT02838420

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Randomized, Multicenter, Phase III, Open-Label Study of Alectinib Versus Crizotinib in Asian Patients With Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer

This randomized, multicenter, Phase III, open-label study will evaluate the efficacy and safety of alectinib versus crizotinib and to evaluate the pharmacokinetics of alectinib in asian participants with treatment-naive ALK-positive advanced NSCLC. Participants will be randomized 2:1 into one of the two treatment groups to receive either alectinib (600 milligrams [mg] twice daily [BID]) or crizotinib (250 mg BID) orally, respectively.

NCT02838420 Anaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer
MeSH:Lymphoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO:Lymphoma Neoplasm of the lung Non-small cell lung carcinoma

2 Interventions

Name: Alectinib

Description: Alectinib capsules will be administered orally at a dose of 600 mg BID until disease progression, unacceptable toxicity withdrawal of consent, or death.
Type: Drug
Group Labels: 1

Alectinib

Name: Crizotinib

Description: Crizotinib capsules will be administered orally at a dose of 250 mg BID until disease progression, unacceptable toxicity withdrawal of consent, or death.
Type: Drug
Group Labels: 1

Crizotinib


Primary Outcomes

Description: PFS was defined as the time (in months) from randomization to the first documentation of disease progression, as determined by the investigators, or to death from any cause, whichever occurred first.

Measure: Progression-Free Survival (PFS) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumor (RECIST) v1.1

Time: From the date of randomization to the date of the first documented disease progression or death, whichever occurred first (up to overall period of approximately 40 months)

Secondary Outcomes

Description: PFS was defined as the time (in months) from randomization to the first documentation of disease progression, as determined by an independent review committee, or to death from any cause, whichever occurred first.

Measure: PFS as Determined by Independent Review Committee (IRC) Using RECIST v1.1

Time: Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)

Measure: Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by Investigator Using RECIST v1.1

Time: Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)

Measure: Time to Progression of Disease in the CNS as Determined by IRC Using RECIST v1.1

Time: Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)

Measure: Time to Progression of Disease in the CNS as Determined by IRC Using Response Assessment in Neuro-Oncology (RANO)

Time: Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)

Measure: Duration of Response (DOR) Assessed by Investigator Using RECIST v1.1

Time: Baseline, Week 8, thereafter every 8 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)

Measure: Overall Survival Time

Time: Baseline, until death (up to overall period of approximately 40 months)

Description: An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

Measure: Percentage of Participants With Non-serious Adverse Events and Serious Adverse Events

Time: Up to overall period of approximately 40 months

Measure: Time to Deterioration Assessed Using EORTC Quality of Life Questionnaire-Core (QLQ-C30) Score

Time: Baseline, Week 4, thereafter every 4 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)

Measure: Time to Deterioration Assessed Using EORTC Quality of Life Questionnaire-Lung Cancer Module (QLQ-LC13) Score

Time: Baseline, Week 4, thereafter every 4 weeks until disease progression, death or withdrawal from the study and 4 weeks after permanent discontinuation (up to overall period of approximately 40 months)

Description: AUC was collected for both alectinib and its major metabolite, M4, and was based on their concentrations in plasma over time.

Measure: Area Under the Plasma Concentration-time Curve (AUC) of Alectinib and Its Metabolite

Time: Baseline and Week 4 predose (within 2 hours before administration of study drug)

Description: Cmax was collected for both alectinib and its major metabolite, M4, and was based on their concentrations in plasma over time.

Measure: Maximum Plasma Concentration Observed (Cmax) of Alectinib and Its Metabolite

Time: Baseline and Week 4 predose (within 2 hours before administration of study drug)

Description: Tmax was collected for both alectinib and its major metabolite, M4, and was based on their concentrations in plasma over time.

Measure: Time to Cmax (Tmax) of Alectinib and Its Metabolite

Time: Baseline and Week 4 predose (within 2 hours before administration of study drug)

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 P4503A

Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception Exclusion Criteria: - A malignancy within the previous 3 years (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal (GI) cancer by endoscopic resection, in situ carcinoma of the cervix, or any cured cancer that is considered to have no impact in progression-free survival (PFS) or overall survival (OS) 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: - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than (>) 3× the upper limit of normal (ULN; >=5×ULN for participants with concurrent liver metastases) confirmed on two consecutive measurements; or - 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 - Acute viral or active autoimmune, alcoholic, or other types of hepatitis - National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 Grade 3 or higher toxicities because of any previous therapy (e.g., radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication - History of organ transplant - Co-administration of anti-cancer therapies other than those administered in this study - Baseline QTc >470 ms or symptomatic bradycardia - Administration of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the receiving the first dose of study treatment and during treatment with alectinib or crizotinib - Administration of agents with potential QT interval prolonging effects within 14 days prior to receiving the first dose of study drug - History of hypersensitivity to any of the additives in the alectinib or crizotinib drug formulation - Pregnant or lactating - Known human immunodeficiency virus (HIV-positivity or acquired immunodeficiency syndrome (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, in the opinion of the Principal Investigator, pose an unacceptable risk to the participant in this study - Any psychological, familial, sociological, or geographical condition that potentially hampers compliance with the study protocol requirements or follow-up procedures; those conditions should be discussed with the participant before study entry Inclusion Criteria: - Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive as assessed by the Ventana immunohistochemistry (IHC) test. --- P4503A ---

Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception Exclusion Criteria: - A malignancy within the previous 3 years (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal (GI) cancer by endoscopic resection, in situ carcinoma of the cervix, or any cured cancer that is considered to have no impact in progression-free survival (PFS) or overall survival (OS) 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: - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than (>) 3× the upper limit of normal (ULN; >=5×ULN for participants with concurrent liver metastases) confirmed on two consecutive measurements; or - 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 - Acute viral or active autoimmune, alcoholic, or other types of hepatitis - National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 Grade 3 or higher toxicities because of any previous therapy (e.g., radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication - History of organ transplant - Co-administration of anti-cancer therapies other than those administered in this study - Baseline QTc >470 ms or symptomatic bradycardia - Administration of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the receiving the first dose of study treatment and during treatment with alectinib or crizotinib - Administration of agents with potential QT interval prolonging effects within 14 days prior to receiving the first dose of study drug - History of hypersensitivity to any of the additives in the alectinib or crizotinib drug formulation - Pregnant or lactating - Known human immunodeficiency virus (HIV-positivity or acquired immunodeficiency syndrome (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, in the opinion of the Principal Investigator, pose an unacceptable risk to the participant in this study - Any psychological, familial, sociological, or geographical condition that potentially hampers compliance with the study protocol requirements or follow-up procedures; those conditions should be discussed with the participant before study entry Anaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer Lymphoma Lung Neoplasms Carcinoma, Non-Small-Cell Lung null --- P4503A ---



HPO Nodes


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