Phase III Study Comparing Alectinib With Crizotinib Currently In Prgogress

This randomized, active controlled, multicenter Phase III open-label study is de signed to evaluate the efficacy and safety of alectinib compared with critozinib treatment in patients with treatment-naive ALK-positive advanced NSCLC. Patient s will be randomized in a 1:1 ratio to receive either alectinib, 600 mg orally t wice daily (BID), or critozinib, 250 mg orally BID. Patients will receive treatm ent until disease progression, unacceptable toxicity, consent withdrawal or deat h occurs. The study is expected to last approximately 42 months.



ConditionInterventionPhaseNon-Small Cell Lung Cancer
Drug: alectinib
Drug: crizotinib
Phase 3


Study Type:InterventionalStudy Design:Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: TreatmentOfficial Title:A RANDOMIZED, MULTICENTER, PHASE III, OPEN-LABEL STUDY OF ALECTINIB VERSUS CRIZOTINIB IN TREATMENT-NAÏVE ANAPLASTIC LYMPHOMA KINASE-POSITIVE ADVANCED NON-SMALL CELL LUNG CANCER
Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer Lymphoma
Drug Information available for: Crizotinib
Genetic and Rare Diseases Information Center resources: Lymphosarcoma
U.S. FDA Resources 

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:

• Objective response rate (ORR) 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 IRC using RECIST v. 1.1 criteria [ Time Frame: Up to 33 months ] [ Designated as safety issue: No ]
  
• PFS as assessed by independent review committee (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 ]
  
• Incidence of 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 ]
  
• Patient reported time to deterioration (TTD) as measured by the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30/LC13 [ Time Frame: 33 months ] [ Designated as safety issue: No ]
  
• Patient reported health-related quality of life (HRQoL) as measured by the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30/LC13 [ Time Frame: 33 months ] [ Designated as safety issue: No ]
  

Estimated Enrollment:286Study Start Date:August 2014Estimated Study Completion Date:December 2017Estimated Primary Completion Date:December 2017 (Final data collection date for primary outcome measure)ArmsAssigned InterventionsExperimental: alectinibDrug: alectinib600 mg given orally BID. Taken with food
Active Comparator: crizotinibDrug: crizotinib250 mg given orally BID. Taken with or without food.



  Eligibility

Ages Eligible for Study:  18 Years and olderGenders Eligible for Study:  BothAccepts Healthy Volunteers:  NoCriteria
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 IHC test
• Age >/= 18 years old
• Life expectancy of at least 12 weeks
• ECOG PS of 0-2
• Patients had no prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC
• Adequate renal, hematologic and liver function
• Patients 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 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). Asymptomatic CNS lesions might be treated at the discretion of the investigator per local clinical practice. If patients have neurological symptoms or signs due to CNS metastasis, patients need to complete whole brain radiation or gamma knife irradiation treatment. In all cases, radiation treatment must be completed at least 14 days before enrollment and patients must be clinically stable
• Use of highly effective contraception as defined by the study protocol

Exclusion Criteria:

• Patients with a previous malignancy within the past 3 years are excluded (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal (GI) cancer by endoscopic resection, in situ carcinoma of the cervix, or any cured cancer that is considered to have no impact on PFS and OS for the current NSCLC)
• 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), which have not shown improvement and are strictly considered to interfere with current study medication
• Co-administration of anti-cancer therapies other than those administered in this study.
• Patients with baseline QTc > 470 ms or symptomatic bradycardia
• Receipt of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the first dose until the end of study treatment except for oral corticosteroids up to 20 mg of prednisolone equivalent per day
• Receipt of any drug with potential QT interval prolonging effects within 14 days prior to the first dose until the end of study treatment
• Pregnant or breast-feeding women
• 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 patient in this study

  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

Contacts
Contact: Reference Study ID Number: BO28984 www.roche.com/about_roche/roche_worldwide.htm888-662-6728 (U.S. Only)[email protected]
  Show 174 Study Locations 
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director:Clinical TrialsHoffmann-La Roche
  More Information
No publications provided 

Responsible Party:Hoffmann-La RocheClinicalTrials.gov Identifier:NCT02075840     History of ChangesOther Study ID Numbers:BO28984, 2013-004133-33Study First Received:February 27, 2014Last Updated:January 19, 2015Health Authority:United States: Food and Drug Administration

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


ClinicalTrials.gov processed this record on February 02, 2015