A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants

• Register: ClinicalTrials.gov
• Last refreshed on: 27 February 2024
• Main ID: NCT02075840
• Date of registration: 27/02/2014
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants ALEX
• Scientific 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
• Date of first enrolment: August 19, 2014
• Target sample size: 303
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02075840
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Australia, Bosnia and Herzegovina, Brazil, Canada, Chile, China, Costa Rica, Denmark, Dominican Republic, Egypt, France, Germany, Greece, Guatemala, Hong Kong, Israel, Italy, Korea, Republic of, Mexico, New Zealand, Peru, Poland, Portugal, Russian Federation, Serbia, Singapore, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion 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

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Non-Small Cell Lung Cancer

Intervention(s)

Drug: Crizotinib

Drug: Alectinib

Primary Outcome(s)

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)]

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)]

Secondary Outcome(s)

HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder [Time Frame: Baseline, every 4 weeks until disease progression (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)]

Percentage of Participants With Adverse Events [Time Frame: Baseline up to 28 months in the crizotinib arm and up to 30 months in the alectinib arm]

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)]

Percentage of Participants With CNS ORR of CR or PR IRC-assessed 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)]

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

Overall Survival (OS) [Time Frame: From randomization until death (up to 43 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)]

HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea [Time Frame: Baseline, every 4 weeks until disease progression (up to 33 months)]

Percentage of Participants With PFS Event by IRC [Time Frame: Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 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)]

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 Coughing [Time Frame: Baseline, every 4 weeks until disease progression (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)]

HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest [Time Frame: Baseline, every 4 weeks until disease progression (up to 33 months)]

Percentage of Participants With OS Event [Time Frame: From randomization until death (up to 43 months)]

CNS DOR IRC-assessed According to RECIST v1.1 Criteria [Time Frame: 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 [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)]

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)]

Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria [Time Frame: 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 [Time Frame: Randomization to the first occurrence of disease progression in the CNS (assessed every 8 weeks up to 33 months)]

Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30) [Time Frame: Baseline, every 4 weeks until disease progression (up to 33 months)]

Duration of Response (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators [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)]

Percentage of Participants With 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)]

PFS Independent Review Committee (IRC)-Assessed [Time Frame: Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks 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)]

Secondary ID(s)

2013-004133-33

BO28984

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 15/03/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02075840