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ALEX Study: A Randomized, Phase III Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02075840
First received: February 27, 2014
Last updated: September 1, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Alectinib
Drug: Crizotinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Health-related quality of life (HRQoL) by EORTC quality of life questionnaire C30 [ Time Frame: 33 months ] [ Designated as safety issue: No ]
  • HRQoL by EORTC quality of life questionnaire LC13 [ Time Frame: 33 months ] [ Designated as safety issue: No ]
  • Percentage of participants with objective response as determined by the investigators according to RECIST v. 1.1 criteria [ Time Frame: Up to 33 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • PFS as assessed by IRC according to RECIST v. 1.1 criteria [ Time Frame: Up to 33 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Overall survival, defined as the time from randomization until death from any cause [ Time Frame: Up to 42 months ] [ Designated as safety issue: No ]
  • Percentage of participants with adverse events [ Time Frame: 42 months ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve (AUC) of alectinib [ Time Frame: Up to 33 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Time to deterioration by EORTC quality of life questionnaire lung cancer module 13 (LC13) [ Time Frame: 33 months ] [ Designated as safety issue: No ]

Enrollment: 303
Study Start Date: August 2014
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alectinib
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.
Drug: Alectinib
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.
Other Name: RO5424802
Active Comparator: Crizotinib
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.
Drug: Crizotinib
Participants will receive Crizotinib 250 mg capsules orally BID from visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02075840

  Show 161 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02075840     History of Changes
Other Study ID Numbers: BO28984  2013-004133-33 
Study First Received: February 27, 2014
Last Updated: September 1, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Crizotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016