A Study to Evaluate and Compare the Efficacy and Safety of Alectinib Versus Crizotinib and to Evaluate the Pharmacokinetics of Alectinib in Asian Participants With Treatment-Naive Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small Cell Lung Cancer (NSCLC)

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Brief Title

A Study to Evaluate and Compare the Efficacy and Safety of Alectinib Versus Crizotinib and to Evaluate the Pharmacokinetics of Alectinib in Asian Participants With Treatment-Naive Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small Cell Lung Cancer (NSCLC)

Official Title

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

Brief Summary

      This randomized, multicenter, Phase III, open-label study will evaluate the efficacy and
      safety of alectinib versus crizotinib and to evaluate the pharmacokinetics of alectinib in
      asian participants with treatment-naive ALK-positive advanced NSCLC. Participants will be
      randomized 2:1 into one of the two treatment groups to receive either alectinib (600
      milligrams [mg] twice daily [BID]) or crizotinib (250 mg BID) orally, respectively.
    


Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Progression-Free Survival (PFS) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumor (RECIST) v1.1

Secondary Outcome

 PFS as Determined by Independent Review Committee (IRC) Using RECIST v1.1

Condition

Anaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer

Intervention

Alectinib

Study Arms / Comparison Groups

 Alectinib
Description:  Participants will receive alectinib capsules orally at a dose of 600 mg BID with food until disease progression, unacceptable toxicity withdrawal of consent, or death.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

187

Start Date

August 3, 2016

Completion Date

December 6, 2019

Primary Completion Date

May 31, 2018

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. Sufficient
             tumor tissue available to perform ALK IHC is required. Ventana IHC testing will be
             performed at the designated central laboratory

          -  Life expectancy of at least 12 weeks

          -  Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2

          -  No history of receiving systemic treatment for advanced, recurrent (Stage IIIB not
             amenable for multimodality treatment) or metastatic (Stage IV) NSCLC

          -  Adequate hematologic function: Platelet count greater than equal to (>=) 100×10^9 per
             liter (/L); absolute neutrophil count (ANC) >=1500 cells per microliter (cells/mcL);
             hemoglobin>=9.0 grams per deciliter (g/dL)

          -  Adequate renal function: an estimated glomerular filtration rate (eGFR) calculated
             using the Modification of Diet in Renal Disease (MDRD) formula of >=45 milliliters per
             minute per 1.73 square meter

          -  Participants must have recovered from effects of any major surgery or significant
             traumatic injury at least 28 days before receiving the first dose of study treatment

          -  Measurable disease (by Response Evaluation Criteria in Solid Tumors version 1.1
             [RECIST v1.1]) before administration of study treatment

          -  Previous brain or leptomeningeal metastases are allowed if the participant is
             asymptomatic (e.g., diagnosed incidentally at study baseline). Asymptomatic central
             nervous system (CNS) lesions may be treated at the discretion of the investigator as
             per local clinical practice. If participant has neurological symptoms or signs because
             of CNS metastasis, the participant must complete whole-brain radiation or gamma knife
             irradiation treatment. In all cases, radiation treatment must be completed >=14 days
             before enrollment and disease must be clinically stable

          -  For all females of childbearing potential, a negative serum pregnancy test result must
             be obtained within 3 days prior to starting study treatment

          -  For women who are not postmenopausal (>=12 months of non-therapy-induced amenorrhea)
             or surgically sterile (absence of ovaries and/or uterus), agreement to remain
             abstinent or use single or combined contraceptive methods that result in a failure
             rate of <1% per year during the treatment period and for at least 3 months after the
             last dose of study drug. Abstinence is acceptable only if it is in line with the
             preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar,
             ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable
             methods of contraception. Examples of contraceptive methods with a failure rate of <1%
             per year include tubal ligation, male sterilization, hormonal implants, established,
             proper use of combined oral or injected hormonal contraceptives, and certain
             intrauterine devices. Alternatively, two methods (e.g., two barrier methods such as a
             condom and a cervical cap) may be combined to achieve a failure rate of <1% per year.
             Barrier methods must always be supplemented with the use of a spermicide

          -  For men, agreement to remain abstinent or use a condom plus an additional
             contraceptive method that together result in a failure rate of <1% per year during the
             treatment period and for at least 3 months after the last dose of study drug.
             Abstinence is acceptable only if it is in line with the preferred and usual lifestyle
             of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
             postovulation methods) and withdrawal are not acceptable methods of contraception

        Exclusion Criteria:

          -  A malignancy within the previous 3 years (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
             in progression-free survival (PFS) or overall survival (OS) for the current NSCLC)

          -  Any GI disorder that may affect absorption of oral medications, such as malabsorption
             syndrome or status post-major bowel resection

          -  Liver disease characterized by:

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than (>) 3×
             the upper limit of normal (ULN; >=5×ULN for participants with concurrent liver
             metastases) confirmed on two consecutive measurements; or

          -  Impaired excretory function (e.g., hyperbilirubinemia), synthetic function, or other
             conditions of decompensated liver disease such as coagulopathy, hepatic
             encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices; or

          -  Acute viral or active autoimmune, alcoholic, or other types of hepatitis

          -  National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
             Grade 3 or higher toxicities because of any previous therapy (e.g., radiotherapy)
             (excluding alopecia), which have not shown improvement and are strictly considered to
             interfere with current study medication

          -  History of organ transplant

          -  Co-administration of anti-cancer therapies other than those administered in this study

          -  Baseline QTc >470 ms or symptomatic bradycardia

          -  Administration of strong/potent cytochrome P4503A inhibitors or inducers within 14
             days prior to the receiving the first dose of study treatment and during treatment
             with alectinib or crizotinib

          -  Administration of agents with potential QT interval prolonging effects within 14 days
             prior to receiving the first dose of study drug

          -  History of hypersensitivity to any of the additives in the alectinib or crizotinib
             drug formulation

          -  Pregnant or lactating

          -  Known human immunodeficiency virus (HIV-positivity or acquired immunodeficiency
             syndrome (AIDS)-related illness

          -  Any clinically significant concomitant disease or condition 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 that potentially
             hampers compliance with the study protocol requirements or follow-up procedures; those
             conditions should be discussed with the participant before study entry
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Clinical Trials, , 

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT02838420

Organization ID

YO29449


Responsible Party

Sponsor

Study Sponsor

Hoffmann-La Roche


Study Sponsor

Clinical Trials, Study Director, Hoffmann-La Roche


Verification Date

September 2019