A Study of Alectinib (RO5424802) in Participants With Non-Small Cell Lung Cancer Who Have Anaplastic Lymphoma Kinase (ALK) Mutation and Failed Crizotinib Treatment

NCT ID: NCT01801111

Last Updated: 2018-11-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

138 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-06-20

Study Completion Date

2017-10-27

Brief Summary

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This open-label, non-randomized, multicenter, Phase 1/2 study will evaluate the safety and efficacy of alectinib in participants with non-small cell lung cancer who have ALK mutation and failed crizotinib treatment. In Part 1, cohorts of participants will receive escalating doses of alectinib orally twice daily. In Part 2, participants will receive the recommended phase 2 dose (RP2D) of alectinib as determined in Part 1. Treatment will continue in Part 1 and Part 2 on the same dose until disease progression. In Part 3, following disease progression, participants without epidermal growth factor receptor (EGFR) mutation will be offered continued treatment with alectinib, participants with EGFR mutations will be offered a combination of alectinib and erlotinib.

Detailed Description

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Conditions

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Non-Small-Cell Lung Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Alectinib

Participants will receive alectinib treatment continuously starting from Day 1 Cycle 1 (in 28-day cycles) until disease progression, death, or withdrawal for any other reasons, whichever occurs first. After PD, participants without EGFR mutation will continue treatment with alectinib alone and participants with EGFR mutation will receive alectinib in combination with erlotinib as per discretion of the treating physician.

Group Type EXPERIMENTAL

Erlotinib

Intervention Type DRUG

Erlotinib will be administered at a dose of 100 mg via tablet, orally, once daily in combination with alectinib to participants who progressed on alectinib alone treatment as per treating physician discretion.

Alectinib

Intervention Type DRUG

Alectinib will be administered at a dose of 600 milligrams (mg) via capsule, orally, twice daily.

Interventions

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Erlotinib

Erlotinib will be administered at a dose of 100 mg via tablet, orally, once daily in combination with alectinib to participants who progressed on alectinib alone treatment as per treating physician discretion.

Intervention Type DRUG

Alectinib

Alectinib will be administered at a dose of 600 milligrams (mg) via capsule, orally, twice daily.

Intervention Type DRUG

Other Intervention Names

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Tarceva RO5452802

Eligibility Criteria

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Inclusion Criteria

* Locally advanced or metastatic non-small cell lung cancer (stage IIIB or IV by American Joint Committee on Cancer \[AJCC\])
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Documented ALK rearrangement based on Food and Drug Administration (FDA)-approved test
* Prior treatment with crizotinib and progression according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1) criteria. Participants had to have a minimum 1-week wash-out period between the last dose of crizotinib and the first dose of study treatment. Participants can either be chemotherapy-naïve or have received at least one line of platinum-based chemotherapy
* Adequate hematologic, hepatic, and renal function
* Participants with brain or leptomeningeal metastases are allowed if protocol defined criteria are met
* Measurable disease according to RECIST v1.1 prior to administration of first dose of study drug

Exclusion Criteria

* Receipt of any other ALK inhibitors in addition to crizotinib
* Receipt of any prior cytotoxic chemotherapy for ALK-positive NSCLC within 4 weeks prior to the first dose of study drug
* Participants who received crizotinib or any other tyrosine kinase inhibitors need to have a minimum 1-week washout period before the first dose of study drug
* Active or uncontrolled infectious diseases requiring treatment
* National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) Grade 3 or higher toxicities due to prior therapy that have not shown improvement and are 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 corrected Q-T interval (QTc) greater than (\>) 470 milliseconds, or baseline symptomatic bradycardia (less than 45 heart beats per minute)
* Pregnant or breastfeeding women
* Known Human Immunodeficiency Virus (HIV) positivity or Acquired Immunodeficiency Syndrome (AIDS)-related illness
* History of hypersensitivity to any of the additives in the alectinib formulation
* Any clinically significant concomitant disease or condition that could interfere with, or for which treatment might interfere with, the conduct of the study, or absorption of oral medications, or that would, in the opinion of the principal investigator, pose an unacceptable risk to the participant in the study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

St. Jude Heritage Healthcare

Fullerton, California, United States

Site Status

UC Irvine Medical Center

Orange, California, United States

Site Status

Sharp Memorial Hospital

San Diego, California, United States

Site Status

Coastal Integrative Cancer Care

San Luis Obispo, California, United States

Site Status

UCLA Cancer Center; Premiere Oncology, A Medical Corporation

Santa Monica, California, United States

Site Status

Advanced Medical Specialties

Miami, Florida, United States

Site Status

Florida Hospital Cancer Inst

Orlando, Florida, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Midwestern Regional Medical Center; Office of Research

Zion, Illinois, United States

Site Status

Washington University; Wash Uni. Sch. Of Med

St Louis, Missouri, United States

Site Status

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States

Site Status

Columbia University Medical Center; Department of Hematology/Oncology

New York, New York, United States

Site Status

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Site Status

Texas Oncology, P.A.

Dallas, Texas, United States

Site Status

Cancer Care Centers of South Texas

San Antonio, Texas, United States

Site Status

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status

Prince Charles Hospital

Chermside, Queensland, Australia

Site Status

Townsville General Hospital

Douglas, Queensland, Australia

Site Status

UZ Antwerpen

Edegem, , Belgium

Site Status

UZ Gent

Ghent, , Belgium

Site Status

AZ Delta (Campus Wilgenstraat)

Roeselare, , Belgium

Site Status

University Hospital Herlev

Herlev, , Denmark

Site Status

CHU Angers - Hôpital Hôtel Dieu

Angers, , France

Site Status

Hopital Morvan

Brest, , France

Site Status

Centre Francois Baclesse

Caen, , France

Site Status

Centre Georges François Leclerc; Service Pharmacie, Bp 77980

Dijon, , France

Site Status

CHU de Grenoble - Hôpital Nord; Service d'Oncologie Thoracique

Grenoble, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Centre Leon Berard

Lyon, , France

Site Status

Hôpital Nord - AP-HM Marseille#; Gastroenterology and Hepatology

Marseille, , France

Site Status

Groupe Hospitalier Sud - Hôpital Haut Lévêque

Pessac, , France

Site Status

Hopital Pontchaillou - CHU de Rennes

Rennes, , France

Site Status

ICO Rene Gauducheau; CEC

Saint-Herblain, , France

Site Status

Nouvel Hopital Civil - CHU Strasbourg

Strasbourg, , France

Site Status

CHU de Toulouse - Hôpital Larrey

Toulouse, , France

Site Status

Charité Campus Virchow-Klinikum; Department of Cardiology

Berlin, , Germany

Site Status

Klinikum Koeln-Merheim

Cologne, , Germany

Site Status

Diakonie Kaiserswerth; Florence-Nightingale-Krankenhaus

Düsseldorf, , Germany

Site Status

LungenClinic Großhansdorf

Großhansdorf, , Germany

Site Status

Lungenklinik Hemer

Hemer, , Germany

Site Status

Mathias-Spital Rheine

Rheine, , Germany

Site Status

A.O. Universitaria Di Parma

Parma, Emilia-Romagna, Italy

Site Status

Irccs Centro Di Riferimento Oncologico (CRO)

Aviano, Friuli Venezia Giulia, Italy

Site Status

Istituto Nazionale Tumori Regina Elena IRCCS

Rome, Lazio, Italy

Site Status

AO San Camillo Forlanini

Rome, Lazio, Italy

Site Status

Ospedale San Raffaele

Milan, Lombardy, Italy

Site Status

Istituto Europeo Di Oncologia

Milan, Lombardy, Italy

Site Status

Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)

Milan, Lombardy, Italy

Site Status

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, Italy

Site Status

Ospedale Versilia

Lido di Camaiore, Tuscany, Italy

Site Status

Presidio Ospedaliero Campo di Marte

Lucca, Tuscany, Italy

Site Status

Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia

Perugia, Umbria, Italy

Site Status

Centre Hospitalier de Luxembourg

Luxembourg, , Luxembourg

Site Status

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

Site Status

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Site Status

Maastricht University Medical Centre; Afdeling Klinische Farmacie en Toxicologie

Maastricht, , Netherlands

Site Status

FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"; Chemotherapy Departement

Moskva, Moscow Oblast, Russia

Site Status

National University Hospital; Investigational Medicine Unit

Singapore, , Singapore

Site Status

Johns Hopkins Singapore

Singapore, , Singapore

Site Status

National Cancer Center

Gyeonggi-do, , South Korea

Site Status

Seoul National University Bundang Hospital

Gyeonggi-do, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital, Yonsei University Health System; Pharmacy

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Hospital General Univ. de Alicante

Alicante, , Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital Universitario Quiron Dexeus

Barcelona, , Spain

Site Status

Hospital Clínic i Provincial de Barcelona

Barcelona, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status

Hospital Universitario Clínico San Carlos; Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Regional Universitario de Malaga

Málaga, , Spain

Site Status

Hosp Clinico Univ Lozano Blesa

Zaragoza, , Spain

Site Status

Karolinska

Stockholm, , Sweden

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

National Cheng Kung Univ Hosp

Tainan City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Aberdeen Royal Infirmary

Aberdeen, , United Kingdom

Site Status

Royal Marsden Hospital;Dept of Haematology Oncology Research

London, , United Kingdom

Site Status

Royal Marsden Hospital - London

London, , United Kingdom

Site Status

Countries

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United States Australia Belgium Denmark France Germany Italy Luxembourg Netherlands Russia Singapore South Korea Spain Sweden Taiwan United Kingdom

References

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Ou SI, Gadgeel SM, Barlesi F, Yang JC, De Petris L, Kim DW, Govindan R, Dingemans AM, Crino L, Lena H, Popat S, Ahn JS, Dansin E, Mitry E, Muller B, Bordogna W, Balas B, Morcos PN, Shaw AT. Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer. Lung Cancer. 2020 Jan;139:22-27. doi: 10.1016/j.lungcan.2019.10.015. Epub 2019 Oct 14.

Reference Type DERIVED
PMID: 31706099 (View on PubMed)

Morcos PN, Nueesch E, Jaminion F, Guerini E, Hsu JC, Bordogna W, Balas B, Mercier F. Exposure-response analysis of alectinib in crizotinib-resistant ALK-positive non-small cell lung cancer. Cancer Chemother Pharmacol. 2018 Jul;82(1):129-138. doi: 10.1007/s00280-018-3597-5. Epub 2018 May 10.

Reference Type DERIVED
PMID: 29748847 (View on PubMed)

Gadgeel SM, Shaw AT, Govindan R, Gandhi L, Socinski MA, Camidge DR, De Petris L, Kim DW, Chiappori A, Moro-Sibilot DL, Duruisseaux M, Crino L, De Pas T, Dansin E, Tessmer A, Yang JC, Han JY, Bordogna W, Golding S, Zeaiter A, Ou SI. Pooled Analysis of CNS Response to Alectinib in Two Studies of Pretreated Patients With ALK-Positive Non-Small-Cell Lung Cancer. J Clin Oncol. 2016 Dec;34(34):4079-4085. doi: 10.1200/JCO.2016.68.4639. Epub 2016 Oct 31.

Reference Type DERIVED
PMID: 27863201 (View on PubMed)

Other Identifiers

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2012-004455-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NP28673

Identifier Type: -

Identifier Source: org_study_id

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