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

Hoffmann-La Roche98 sites in 15 countries303 target enrollmentAugust 19, 2014

ConditionsNon-Small Cell Lung Cancer

InterventionsAlectinib Crizotinib

DrugsAlectinib Crizotinib

Overview

Phase: Phase 3
Intervention: Alectinib
Conditions: Non-Small Cell Lung Cancer
Sponsor: Hoffmann-La Roche
Enrollment: 303
Locations: 98
Primary Endpoint: Progression-Free Survival (PFS) by Investigator Assessment
Status: Completed
Last Updated: 9 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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, withdrawal of consent, or death. The study is expected to last approximately 144 months.

Registry

clinicaltrials.gov

Start Date

August 19, 2014

End Date

April 28, 2025

Last Updated

9 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

Alectinib

Participants will receive alectinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

Intervention: Alectinib

Crizotinib

Participants will receive crizotinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

Intervention: Crizotinib

Outcomes

Primary Outcomes

Progression-Free Survival (PFS) by Investigator Assessment

Time Frame: Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)

PFS was assessed as time to disease progression or death whichever occurred first by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.

Percentage of Participants With PFS Event by Investigator Assessment

Time Frame: Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)

PFS was assessed percentage of participants with disease progression or death whichever occurred first by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.

Secondary Outcomes

PFS Independent Review Committee (IRC)-Assessed(Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months))
Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria(Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months))
Percentage of Participants With PFS Event by IRC(Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months))
Duration of Response (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators(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 (OS)(From randomization until death (up to 43 months))
Percentage of Participants With Adverse Events(Baseline up to 28 months in the crizotinib arm and up to 30 months in the alectinib arm)
Area Under The Concentration-Time Curve (AUC) of Alectinib(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))
Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria(Randomization to CNS PD as first occurrence of disease progression (assessed every 8 weeks up to 33 months))
Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using Revised Assessment in Neuro Oncology (RANO) Criteria(Randomization to the first occurrence of disease progression in the CNS (assessed every 8 weeks up to 33 months))
Percentage of Participants With Objective Response Rate (ORR) of Complete Response (CR) or Partial Response (PR) as Determined by The Investigators According to RECIST V1.1 Criteria(Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months))
Percentage of Participants With OS Event(From randomization until death (up to 43 months))
CNS DOR IRC-assessed According to RECIST v1.1 Criteria(First occurrence of CNS objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months))
Time to Reach Cmax (Tmax) of Alectinib(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(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(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(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)(Baseline, every 4 weeks until disease progression (up to 33 months))
Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30)(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)(Baseline, every 4 weeks until disease progression (up to 33 months))
Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)(Baseline, every 4 weeks until disease progression (up to 33 months))
Maximum Concentration (Cmax) of Alectinib(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))
Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score(Baseline, every 4 weeks until disease progression (up to 33 months))
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing(Baseline, every 4 weeks until disease progression (up to 33 months))
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea(Baseline, every 4 weeks until disease progression (up to 33 months))
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder(Baseline, every 4 weeks until disease progression (up to 33 months))
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest(Baseline, every 4 weeks until disease progression (up to 33 months))