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
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants will receive Alectinib orally BID with food in the morning or evening from visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
alectinib RO5424802
Participants will receive Alectinib 600 mg (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 orally BID with or without food in the morning or evening 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) v. 1.1 criteria
time frame: Up to 33 months

Secondary Outcomes

Measure
Health-related quality of life (HRQoL) by EORTC quality of life questionnaire C30
time frame: 33 months
HRQoL by EORTC quality of life questionnaire LC13
time frame: 33 months
Percentage of participants with objective response as determined by the investigators according to RECIST v. 1.1 criteria
time frame: Up to 33 months
Time to central nervous system (CNS) progression as determined by independent review committee (IRC) using RECIST v. 1.1 criteria
time frame: Up to 33 months
PFS as assessed by IRC according to RECIST v. 1.1 criteria
time frame: Up to 33 months
Duration of response defined as time from when response (complete or partial [CR or PR]) was first documented until first documented disease progression or death, whichever occurs first
time frame: Up to 33 months
Overall survival, defined as the time from randomization until death from any cause
time frame: Up to 42 months
Percentage of participants with adverse events
time frame: 42 months
Area under the concentration-time curve (AUC) of alectinib
time frame: 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: 33 months
Time to deterioration by EORTC quality of life questionnaire lung cancer module 13 (LC13)
time frame: 33 months

Eligibility Criteria

Male or female 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 - Age >/=18 years old - 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) 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>470 ms or symptomatic bradycardia - Recepient of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the first dose until the end of study treatment - Recepient of any drug with potential QT interval prolonging effects within 14 days prior to the first dose until the end of study treatment - 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 September 2016.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.
Location data was received from the National Cancer Institute and was last updated in September 2016.