Overview

This trial is active, not recruiting.

Condition non-small cell lung cancer
Treatments alectinib, crizotinib
Phase phase 3
Targets c-MET, ALK, ROS1
Sponsor Hoffmann-La Roche
Start date August 2014
End date March 2017
Trial size 303 participants
Trial identifier NCT02075840, 2013-004133-33, BO28984

Summary

This randomized, active controlled, multicenter phase III open-label study is designed to evaluate the efficacy and safety of alectinib compared with crizotinib treatment in participants with treatment-naive anaplastic lymphoma kinase-positive (ALK-positive) advanced non-small cell lung cancer (NSCLC). Participants will be randomized in a 1:1 ratio to receive either alectinib, 600 milligrams (mg) orally twice daily (BID), or crizotinib, 250 mg orally BID. Participants will receive treatment until disease progression, unacceptable toxicity, consent withdrawal or death. The study is expected to last approximately 42 months.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Primary purpose treatment
Masking no masking
Arm
(Experimental)
Participants will receive alectinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
alectinib RO5424802
Participants will receive alectinib 600 mg orally (four 150 mg capsules) BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
(Active Comparator)
Participants will receive crizotinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
crizotinib
Participants will receive crizotinib 250 mg capsules orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

Primary Outcomes

Measure
Progression-Free Survival (PFS) as Assessed by Investigators According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria
time frame: Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)

Secondary Outcomes

Measure
Percentage of Participants With Objective Response as Determined by The Investigators According to RECIST V1.1 Criteria
time frame: Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Time to Central Nervous System (CNS) Progression as Determined by Independent Review Committee (IRC) Using RECIST V1.1 Criteria
time frame: Randomization to the first occurrence of disease progression in the CNS (assessed every 8 weeks up to 33 months)
PFS as Assessed by IRC According to RECIST V1.1 Criteria
time frame: Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Duration of Response According to RECIST V1.1 Criteria
time frame: First occurrence of objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Overall Survival
time frame: From randomization until death (up to 43 months)
Percentage of Participants With Adverse Events
time frame: Baseline up to 43 months
Area Under The Concentration-Time Curve (AUC) of Alectinib
time frame: Pre-dose (within 2 hours before alectinib) (baseline), 1, 2, 4, 6, and 8 hours post-dose at Visit 0 (first dosing day) and Week 4; Pre-dose (within 2 hours) at Week 8, then every 8 weeks until disease progression or death/withdrawal (up to 33 months)
Maximum Concentration (Cmax) of Alectinib
time frame: Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
Time to Reach Cmax (tmax) of Alectinib
time frame: Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
AUC of Alectinib Metabolite
time frame: Pre-dose (within 2 hours before alectinib) (baseline), 1, 2, 4, 6, and 8 hours post-dose at Visit 0 (first dosing day) and Week 4; Pre-dose (within 2 hours) at Week 8, then every 8 weeks until disease progression or death/withdrawal (up to 33 months)
Cmax of Alectinib Metabolite
time frame: Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
tmax of Alectinib Metabolite
time frame: Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
Time to Deterioration by European Organization for The Research And Treatment of Cancer (EORTC) Quality Of Life Questionnaire Core 30 (C30)
time frame: Baseline, every 4 weeks until disease progression (up to 33 months)
Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)
time frame: Baseline, every 4 weeks until disease progression (up to 33 months)
Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score
time frame: Baseline, every 4 weeks until disease progression (up to 33 months)
HRQoL by EORTC Quality of Life Questionnaire LC13 Score
time frame: Baseline, every 4 weeks until disease progression (up to 33 months)

Eligibility Criteria

All participants at least 18 years old.

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 - Life expectancy of at least 12 weeks - Eastern cooperative oncology group performance status (ECOG PS) of 0-2 - Participants with no prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC - Adequate renal, and hematologic function - Participants must have recovered from effects of any major surgery or significant traumatic injury at least 28 days before the first dose of study treatment - Measurable disease by response evaluation criteria in solid tumors (RECIST) version 1.1 (v1.1) prior to the administration of study treatment - Prior brain or leptomeningeal metastases allowed if asymptomatic (e.g., diagnosed incidentally at study baseline) - Negative pregnancy test for all females of child bearing potential - Use of highly effective contraception as defined by the study protocol Exclusion Criteria: - Participants with a previous malignancy within the past 3 years - Any gastrointestinal (GI) disorder or liver disease - National cancer institute common terminology criteria for adverse events (NCI CTCAE) (version 4.0) Grade 3 or higher toxicities due to any prior therapy (e.g., radiotherapy) (excluding alopecia) - History of organ transplant - Co-administration of anti-cancer therapies other than those administered in this study - Participants with baseline QTc greater than (>) 470 milliseconds or symptomatic bradycardia - Recipient of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the first dose until the end of study treatment - Recipient of any drug with potential QT interval prolonging effects within 14 days prior to the first dose for all participants and while on treatment through the end of the study for crizotinib-treated participants only - History of hypersensitivity to any of the additives in the alectinib and crizotinib drug formulation - Pregnancy or lactation - Any clinically significant disease or condition (or history of) 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 potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the participant before trial entry

Additional Information

Official title Randomized, Multicenter, Phase III, Open-Label Study of Alectinib Versus Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer
Trial information was received from ClinicalTrials.gov and was last updated in February 2017.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.