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

NCT01801111 | Completed Phase 1 Results

• 2 other identifiers: NP286732012-004455-36
• Study Type: interventional
• Target: 138
• Locations: 16 countries
• Sites: 84

Brief Summary

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.

Conditions

Non-Small-Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (4)

• Recommended Phase 2 Dose (RP2D) of Alectinib

  RP2D was to be determined based on the safety and tolerability profile of the study treatment.

  Cycle 1 (up to 28 days)

• Percentage of Participants With Dose Limiting Toxicities (DLTs)

  DLTs were to be assessed based on the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.3 (NCI-CTCAE v 4.3). DLTs: drug-related toxicities that meet any one of the following criteria: Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding; Grade 4 neutropenia continuing for greater than or equal to (\>/=) 7 consecutive days or neutropenic fever; Non-hematological toxicity of Grade 3 or higher; Adverse events that require interruption of treatment for a total of \>/=7 days.

  Cycle 1 (up to 28 days)

• Percentage of Participants Achieving Objective Response (Complete Response [CR] or Partial Response [PR]) as Assessed by Independent Radiological Review Committee (IRC) in Response Evaluable (RE) Population

  Tumor response was assessed by IRC according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments \>/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to less than (\<) 10 millimeters (mm). PR was defined as \>/=30 percent (%) decrease in the sum of diameters (SoD) of target lesions (taking as reference the baseline SoD). The 95% confidence interval (CI) was computed using Clopper-Pearson method.

  Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)

• Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Pretreated Participants

  Tumor response was assessed by IRC according to RECIST v1.1. Objective response was defined as percentage of participants with a CR or PR that was confirmed by repeat assessments \>/=4 weeks after initial documentation. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level; and reduction in all lymph nodes size to \<10 mm. PR was defined as \>/=30% decrease in the SoD of target lesions (taking as reference the baseline SoD). The 95% CI was computed using Clopper-Pearson method.

  Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)

Secondary Outcomes (32)

• Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Naive Participants

  Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)

• Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in RE Population

  Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)

• Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Pretreated Participants

  Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)

• Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Naive Participants

  Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)

• Duration of Response (DoR) as Assessed by IRC in RE Population

  Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)

Study Arms (1)

Alectinib

EXPERIMENTAL

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.

Drug: Erlotinib; Drug: Alectinib

Interventions

Erlotinib 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.

Also known as: Tarceva

Alectinib

Alectinib DRUG

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

Also known as: RO5452802

Alectinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (84)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

St. Jude Heritage Healthcare

Fullerton, California, 92835, United States

Location

UC Irvine Medical Center

Orange, California, 92868, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

Coastal Integrative Cancer Care

San Luis Obispo, California, 93401, United States

Location

UCLA Cancer Center; Premiere Oncology, A Medical Corporation

Santa Monica, California, 90404, United States

Location

Advanced Medical Specialties

Miami, Florida, 33176, United States

Location

Florida Hospital Cancer Inst

Orlando, Florida, 32804, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Midwestern Regional Medical Center; Office of Research

Zion, Illinois, 60099, United States

Location

Washington University; Wash Uni. Sch. Of Med

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89014, United States

Location

Columbia University Medical Center; Department of Hematology/Oncology

New York, New York, 10032, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Texas Oncology, P.A.

Dallas, Texas, 75246, United States

Location

Cancer Care Centers of South Texas

San Antonio, Texas, 78217, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Townsville General Hospital

Douglas, Queensland, 4184, Australia

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

AZ Delta (Campus Wilgenstraat)

Roeselare, 8800, Belgium

Location

University Hospital Herlev

Herlev, 2730, Denmark

Location

CHU Angers - Hôpital Hôtel Dieu

Angers, 49933, France

Location

Hopital Morvan

Brest, 29200, France

Location

Centre Francois Baclesse

Caen, 14076, France

Location

Centre Georges François Leclerc; Service Pharmacie, Bp 77980

Dijon, 21000, France

Location

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

Grenoble, 38043, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

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

Marseille, 13915, France

Location

Groupe Hospitalier Sud - Hôpital Haut Lévêque

Pessac, 33600, France

Location

Hopital Pontchaillou - CHU de Rennes

Rennes, 35033, France

Location

ICO Rene Gauducheau; CEC

Saint-Herblain, 44805, France

Location

Nouvel Hopital Civil - CHU Strasbourg

Strasbourg, 67091, France

Location

CHU de Toulouse - Hôpital Larrey

Toulouse, 31059, France

Location

Charité Campus Virchow-Klinikum; Department of Cardiology

Berlin, 13353, Germany

Location

Klinikum Koeln-Merheim

Cologne, 51109, Germany

Location

Diakonie Kaiserswerth; Florence-Nightingale-Krankenhaus

Düsseldorf, 40489, Germany

Location

LungenClinic Großhansdorf

Großhansdorf, 22927, Germany

Location

Lungenklinik Hemer

Hemer, 58675, Germany

Location

Mathias-Spital Rheine

Rheine, 48431, Germany

Location

A.O. Universitaria Di Parma

Parma, Emilia-Romagna, 43100, Italy

Location

Irccs Centro Di Riferimento Oncologico (CRO)

Aviano, Friuli Venezia Giulia, 33081, Italy

Location

Istituto Nazionale Tumori Regina Elena IRCCS

Rome, Lazio, 00144, Italy

Location

AO San Camillo Forlanini

Rome, Lazio, 00149, Italy

Location

Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

Location

Istituto Europeo Di Oncologia

Milan, Lombardy, 20141, Italy

Location

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

Milan, Lombardy, Italy

Location

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, 50141, Italy

Location

Ospedale Versilia

Lido di Camaiore, Tuscany, 55043, Italy

Location

Presidio Ospedaliero Campo di Marte

Lucca, Tuscany, 55100, Italy

Location

Azienda Ospedaliera di Perugia Ospedale S. Maria della Misericordia

Perugia, Umbria, 06100, Italy

Location

Centre Hospitalier de Luxembourg

Luxembourg, 1210, Luxembourg

Location

Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Maastricht University Medical Centre; Afdeling Klinische Farmacie en Toxicologie

Maastricht, 6229HX, Netherlands

Location

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

Moskva, Moscow Oblast, 115478, Russia

Location

National University Hospital; Investigational Medicine Unit

Singapore, 119074, Singapore

Location

Johns Hopkins Singapore

Singapore, 308433, Singapore

Location

National Cancer Center

Gyeonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital

Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System; Pharmacy

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

Hospital General Univ. de Alicante

Alicante, 03010, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario Quiron Dexeus

Barcelona, 08028, Spain

Location

Hospital Clínic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario La Paz

Madrid, 280146, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Clínico San Carlos; Servicio de Oncologia

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

Hosp Clinico Univ Lozano Blesa

Zaragoza, 50009, Spain

Location

Karolinska

Stockholm, 17176, Sweden

Location

Taichung Veterans General Hospital

Taichung, 407, Taiwan

Location

National Cheng Kung Univ Hosp

Tainan, 00704, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

Location

Royal Marsden Hospital;Dept of Haematology Oncology Research

London, SW3 6HP, United Kingdom

Location

Royal Marsden Hospital - London

London, SW3 6JJ, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 31706099 DERIVED

• 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.

  PMID: 29748847 DERIVED

• 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.

  PMID: 27863201 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride; alectinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Part 1 analysis was not conducted as during the conduct of the study the RP2D was confirmed in study NP28761 (NCT01871805).

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2013
• First Posted: February 28, 2013
• Study Start: June 20, 2013
• Primary Completion: October 24, 2014
• Study Completion: October 27, 2017
• Last Updated: November 2, 2018
• Results First Posted: May 26, 2016

Record last verified: 2018-10

Locations

NL (3); IT (11); KR (6); LU (1); GB (3); US (17); AU (3); DK (1); SG (2); ES (10); SE (1); BE (3); FR (13); DE (6); RU (1); TW (3)