Clinical trial NCT03456076: A Study Comparing Adjuvant Alectinib Versus Adjuvant Platinum-Based Chemotherapy in Patients With ALK Positive Non-Small Cell Lung Cancer
Official title: A Phase III, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Adjuvant Alectinib Versus Adjuvant Platinum-Based Chemotherapy in Patients With Completely Resected Stage IB (Tumors Equal to or Larger Than 4cm) to Stage IIIA Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: NSCLC, alectinib, ALK positive,adjuvant treatment, platinum based chemotherapy, complete resection, Stage IB-IIIA.
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2018-03-07
Enrollment: 257
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized, active-controlled, multicenter, open-label, Phase III study is designed to investigate the efficacy and safety of alectinib compared with platinum-based in the adjuvant setting. Participants in the experimental arm will receive alectinib at 600 mg orally twice daily (BID) taken with food for 24 months.

Participants in the control arm will receive one of the protocol specified platinum based chemotherapy regimens for 4 cycles. Following treatment completion, participants will be followed up for their disease until disease recurrence. At the time of disease recurrence, participants will enter a survival follow-up until death, withdrawal of consent or study closure, whichever occurs earlier.


Eligibility criteria: Key Inclusion Criteria

* Age ≥18 years
* Complete resection of histologically confirmed Stage IB (tumor ≥ 4 cm) to Stage IIIA (T2-3 N0, T1-3 N1, T1-3 N2, T4 N0-1) NSCLC as per Union Internationale Contre le Cancer / American Joint Committee on Cancer, 7th edition, with negative margins, at 4-12 weeks before enrollment
* If mediastinoscopy was not performed preoperatively, it is expected that, at a minimum, mediastinal lymph node systematic sampling will have occurred
* Documented ALK-positive disease according to an FDA-approved and CE-marked test
* Eligible to receive a platinum-based chemotherapy regimen according to the local labels or guidelines
* Eastern Cooperative Oncology Group Performance Status of Grade 0 or 1
* Adequate hematologic and renal function
* For women of childbearing potential: agreement to remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for at least 90 days after the last dose of alectinib or according to local labels or guidelines for chemotherapy
* For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm for at least 90 days after the last dose of alectinib or according to local labels or guidelines for chemotherapy. Men must refrain from donating sperm during this same period
* Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Key Exclusion Criteria

* Pregnant or breastfeeding, or intending to become pregnant during the study or within 90 days after the last dose of alectinib or according to local labels or guidelines for chemotherapy
* Prior adjuvant radiotherapy for NSCLC
* Prior exposure to systemic anti-cancer therapy and ALK inhibitors
* Stage IIIA N2 patients that, in the investigator's opinion, should receive post-operative radiotherapy treatment are excluded from the study
* Known sensitivity to any component of study drug to which the patient may be randomized. This includes, but is not limited to, patients with galactose intolerance, a congenital lactase deficiency or glucose-galactose malabsorption.
* Malignancies other than NSCLC within 5 years prior to enrollment, except for curatively treated basal cell carcinoma of the skin, early gastrointestinal (GI) cancer by endoscopic resection, in situ carcinoma of the cervix, ductal carcinoma in situ, papillary thyroid cancer, or any cured cancer that is considered to have no impact on disease free survival or overall survival 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 aspartate transaminase and alanine transaminase \>= 3 × upper limit of normal or impaired excretory function or synthetic function or other conditions of decompensated liver disease such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, or bleeding from esophageal varices or active viral or active autoimmune, alcoholic, or other types of acute hepatitis
* Japanese patients participating in the serial/intensive PK sample collection only: administration of strong/potent CYP450 3A inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment with alectinib up to Week 3
* Any exclusion criteria based on the local labels or guidelines for chemotherapy regimen
* Patients with symptomatic bradycardia
* History of organ transplant
* Known HIV positivity or 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 pose an unacceptable risk to the patients in this study, in the opinion of the Principal Investigator
* 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 patient before trial entry

Primary outcomes:
measure: Disease-free Survival (DFS), as Assessed by the Investigator
timeFrame: Approximately 58 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From the date of randomization until death due to any cause up to approximately 8 years
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Until 28 days after the last dose of alectinib (up to 2 years) or 28 days after end of last cycle of chemotherapy (up to 4 cycles)
measure: AEs Grade 3-5 With a Difference in Incidence Rate of at Least 2% Between Treatment Arms
timeFrame: Until 28 days after the last dose of alectinib (up to 2 years) or 28 days after end of last cycle of chemotherapy (up to 4 cycles)
measure: Plasma Concentration of Alectinib
timeFrame: Predose (2 hours) Week 3 - Week 96
measure: Plasma Concentration of Alectinib Metabolite M4
timeFrame: Predose (2 hours) Week 3 - Week 96
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Boston
country: United States
facility: MGH Cancer Center
state: Massachusetts
city: Pittsburgh
country: United States
facility: AHN Cancer Institute ? Allegheny General Hospital
state: Pennsylvania
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: St Leonards
country: Australia
facility: GenesisCare North Shore
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Wien
country: Austria
facility: Krankenhaus Nord - Klinik Floridsdorf
city: Gomel
country: Belarus
facility: Healthcare Institution ?Gomel Regional Clinical Oncologic Dispensary?
state: Homyel'skaya Voblasts'
city: Grodno
country: Belarus
facility: Healthcare Institution Grodno University Hospital
state: Hrodzyenskaya Voblasts'
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Oncology Dispensary
state: Vitsyebskaya Voblasts'
city: Sarajevo
country: Bosnia and Herzegovina
facility: Clinical center University of Sarajevo
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Fujian
country: China
facility: Fujian Medical University Union Hospital
city: Guangzhou
country: China
facility: Guangdong General Hospital
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
city: Wuhan City
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Xi'an
country: China
facility: First Affiliated Hospital of Medical College of Xi'an Jiaotong University
city: Odense C
country: Denmark
facility: Odense Universitetshospital, Onkologisk Afdeling R
city: Cairo
country: Egypt
facility: Kasr Eieny Uni Hospital
city: Angers
country: France
facility: CHU Angers
city: Marseille
country: France
facility: Hopital Nord AP-HM
city: Paris
country: France
facility: Hopital Bichat Claude Bernard
city: Villejuif cedex
country: France
facility: Institut Gustave Roussy
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Georgsmarienhütte
country: Germany
facility: Niels-Stensen-Kliniken Franziskus-Hospital Harderberg GmbH
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH
city: Immenhausen
country: Germany
facility: Fachklinik für Lungenerkrankungen
city: Athens
country: Greece
facility: Metropolitan Hospital
city: Thessaloniki
country: Greece
facility: Theageneio Hospital
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Szolnok
country: Hungary
facility: Hetenyi Geza County Hospital
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Napoli
country: Italy
facility: Az. Osp. Monaldi
state: Campania
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini - Unità Operativa Complessa di Pneumologia Oncologica 1
state: Lazio
city: Milano
country: Italy
facility: Irccs Istituto Europeo di Oncologia (IEO)
state: Lombardia
city: Orbassano
country: Italy
facility: Az. Osp. S. Luigi Gonzaga
state: Piemonte
city: Perugia
country: Italy
facility: Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia
state: Umbria
city: Aichi
country: Japan
facility: Aichi Cancer Center
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Hokkaido
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
city: Hyogo
country: Japan
facility: National Hospital Organization Himeji Medical Center
city: Kanagawa
country: Japan
facility: Kanagawa Cancer Center
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Miyagi
country: Japan
facility: Sendai Kousei Hospital
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: Juntendo University Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Tokyo
country: Japan
facility: Tokyo Medical University Hospital
city: Almaty
country: Kazakhstan
facility: Almaty Oncology Center
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Ajou University Medical Center
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Skopje
country: North Macedonia
facility: PHI University Clinic of Radiotherapy and Oncology; Malignant diseases of thorax
city: Skopje
country: North Macedonia
facility: Private Health Organization Acibadem Sistina Hospital
city: Gda?sk
country: Poland
facility: Gdanski Uniwersytet Medyczny
city: Kraków
country: Poland
facility: Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II
city: Olsztyn
country: Poland
facility: Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu
city: Warszawa
country: Poland
facility: Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad
city: Cluj-napoca
country: Romania
facility: Prof Dr I Chiricuta Institute of Oncology
city: Timisoara
country: Romania
facility: Oncomed SRL
city: Moscovskaya Oblast
country: Russian Federation
facility: Moscow City Oncology Hospital #62
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: P.A. Gertsen Cancer Research Inst.
state: Moskovskaja Oblast
city: Sankt-peterburg
country: Russian Federation
facility: SPb City Clin Onc Dsp
state: Sankt Petersburg
city: St. Petersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University
state: Sankt Petersburg
city: St. Petersburg
country: Russian Federation
facility: Scientific Research Oncology Institute named after N.N. Petrov
state: Sankt Petersburg
city: Krasnodar
country: Russian Federation
facility: GUZ Regional clinical hospital # 1
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Foundation - Kaohsiung
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - Linkou
city: Xitun Dist.
country: Taiwan
facility: Taichung Veterans General Hospital
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Adana
country: Turkey
facility: Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital
city: Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital
city: Ankara
country: Turkey
facility: Ankara Ataturk Chest Diseases Training and Research Hospital
city: Istanbul
country: Turkey
facility: Istanbul Uni Cerrahpasa Medical Faculty Hospital
city: Izmir
country: Turkey
facility: Ege Uni Medical Faculty Hospital
city: Izmir
country: Turkey
facility: Izmir Suat Seren Chest Diseases and Surgery Research Hospital
city: Malatya
country: Turkey
facility: Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department
city: Samsun
country: Turkey
facility: Medikal Park Samsun
city: Kapitanovka Village
country: Ukraine
facility: Medical center of Yuriy Spizhenko LLC
state: KIEV Governorate
city: Dnipropetrovsk
country: Ukraine
facility: Chemotherapy SI Dnipropetrovsk MA of MOHU
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Oncological Center
city: Sumy
country: Ukraine
facility: RCI Sumy Regional Clinical Oncological Dispensary
city: Vinnytsia
country: Ukraine
facility: Vinnytsia Regional Clinical Oncology Dispensary
city: London
country: United Kingdom
facility: Guys Hospital
city: Manchester
country: United Kingdom
facility: Wythenshaw Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: