A Study Comparing Adjuvant Alectinib Versus Adjuvant Platinum-Based Chemotherapy in Patients With ALK Positive Non-Small Cell Lung Cancer

Carcinoma, Non-Small-Cell Lung Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03456076
• Other study ID #: BO40336
• Secondary ID: 2017-004331-37
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 16, 2018
• Est. completion date: November 19, 2026

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 257
• Est. completion date: November 19, 2026
• Est. primary completion date: June 26, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Alectnib
Participants will receive alectinib 600 mg orally BID until completion of treatment period (24 months) or recurrence of disease , unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
• Cisplatin
Participants will receive Cisplatin 75 milligrams per square meter (mg/m^2) on Day 1 every 21 days IV intravenously (IV) until completion of treatment period (4 cycles), recurrence of disease, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first."
• Vinorelbine
Participants will receive Vinorelbine 25 mg/m^2 IV on Days 1 and 8 Q21D until completion of treatment period (4 cycles), recurrence of disease, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first.
• Gemcitabine
Participants will receive Gemcitabine 1250 mg/m^2 on Days 1 and 8 Q21D IV until completion of treatment period (4 cycles), recurrence of disease, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first.
• Pemetrexed
Participants will receive 500 mg/m^2 Day 1 Q21D until completion of treatment period (4 cycles), recurrence of disease, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first."
• Carboplatin
For participants who experience unacceptable toxicity with cisplatin, carboplatin can be used.

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Peter MacCallum Cancer Center	North Melbourne	Victoria
Australia	Northern Cancer Institute	St Leonards	New South Wales
Austria	Krankenhaus Nord - Klinik Floridsdorf; Abteilung Pulmologie	Wien
Belarus	Healthcare Institution ?Gomel Regional Clinical Oncologic Dispensary?	Gomel	Homyel'skaya Voblasts'
Belarus	Healthcare Institution Grodno University Hospital; Regional Oncologic Dispensary	Grodno	Hrodzyenskaya Voblasts'
Belarus	Vitebsk Regional Clinical Oncology Dispensary	Vitebsk	Vitsyebskaya Voblasts'
Bosnia and Herzegovina	Clinical center University of Sarajevo	Sarajevo
China	Beijing Cancer Hospital	Beijing
China	Jilin Cancer Hospital	Changchun
China	West China Hospital, Sichuan University	Chengdu
China	Fujian Medical University Union Hospital	Fuzhou City
China	Guangdong General Hospital	Guangzhou
China	Shandong Cancer Hospital	Jinan
China	Shanghai Chest Hospital	Shanghai
China	Zhongshan Hospital Fudan University	Shanghai
China	Shenzhen People's Hospital	Shenzhen
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
China	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an
China	Zhejiang Cancer Hospital	Zhejiang
Denmark	Odense Universitetshospital, Onkologisk Afdeling R	Odense C
Egypt	Kasr Eieny Uni Hospital; Oncology (Nemrock)	Cairo
Egypt	National Cancer Institute	Cairo
France	CHU Angers	Angers
France	Hopital Nord AP-HM	Marseille
France	Hôpital Arnaud de Villeneuve	Montpellier
France	Hopital Bichat Claude Bernard; Oncologie Serv.	Paris
France	Ch De Saint Quentin; Medecine B14	St Quentin
France	Hôpital d'Instruction des Armées de Sainte Anne; Service de Pneumologie	Toulon
France	Institut Gustave Roussy; Pathologie Thoracique	Villejuif cedex
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Niels-Stensen-Kliniken Franziskus-Hospital Harderberg GmbH	Georgsmarienhütte
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg
Germany	Fachklinik für Lungenerkrankungen	Immenhausen
Greece	Metropolitan Hospital	Athens
Greece	Theageneio Hospital	Thessaloniki
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Semmelweis Egyetem, AOK, Pulmonologiai Klinika	Budapest
Hungary	University of Pecs; 1St Department of Medicine	Pecs
Hungary	Hetenyi Geza County Hospital; Onkologiai Kozpont	Szolnok
Israel	Rambam Health Care Campus; Oncology	Haifa
Israel	Meir Medical Center	Kfar- Saba
Italy	Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica	Aviano	Friuli-Venezia Giulia
Italy	A.O. Istituti Ospitalieri - Cremona; S.C. Oncologia	Cremona	Lombardia
Italy	Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia	Milano	Lombardia
Italy	Irccs Ospedale San Raffaele;Oncologia Medica	Milano	Lombardia
Italy	Azienda Osp. Univ di Modena; Dept Onc & Hem	Modena	Emilia-Romagna
Italy	Az. Osp. Monaldi; 1 Pneumologia Oncologica	Napoli	Campania
Italy	Az. Osp. S. Luigi Gonzaga; Malattie Apparato Respiratorio 5 Ad Indirizzo Oncologico	Orbassano	Piemonte
Italy	Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica	Perugia	Umbria
Italy	A.O. Universitaria Pisana-Ospedale Cisanello; Dipartimento Cardio Toracico-Pneumologia Ii	Pisa	Toscana
Italy	Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica	Ravenna	Emilia-Romagna
Italy	Azienda Ospedaliera San Camillo Forlanini - Unità Operativa Complessa di Pneumologia Oncologica 1	Roma	Lazio
Japan	Aichi Cancer Center	Aichi
Japan	National Cancer Center Hospital East	Chiba
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	Hiroshima University Hospital	Hiroshima
Japan	National Hospital Organization Hokkaido Cancer Center	Hokkaido
Japan	National Hospital Organization Himeji Medical Center	Hyogo
Japan	Kanagawa Cancer Center	Kanagawa
Japan	Kumamoto University Hospital	Kumamoto
Japan	Kyoto University Hospital	Kyoto
Japan	Sendai Kousei Hospital	Miyagi
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Okayama University Hospital	Okayama
Japan	Osaka City General Hospital	Osaka
Japan	Shizuoka Cancer Center	Shizuoka
Japan	Juntendo University Hospital	Tokyo
Japan	National Cancer Center Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Tokyo Medical University Hospital	Tokyo
Kazakhstan	Almaty Oncology Center	Almaty
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Ajou University Medical Center	Gyeonggi-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollanam-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
North Macedonia	PHI University Clinic of Radiotherapy and Oncology; Malignant diseases of thorax	Skopje
North Macedonia	Private Health Organization Acibadem Sistina Hospital	Skopje
Poland	Gdanski Uniwersytet Medyczny; Katedra i Klinika Onkologii i Radioterapii	Gda?sk
Poland	Krakowski Szpital Specjalistyczny im sw. Jana Paw?a II; Oddz. Klin. Chir. Klatki Piersiowej i Onkol.	Kraków
Poland	Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie; Oddzial onkologii z pododdzialem chemioterapii	Olsztyn
Poland	Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu	Poznan
Poland	Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad; Klinika Nowot.Pluca i Klatki Piers	Warszawa
Poland	Dolnoslaskie Centrum Chorob Pluc we Wroclawiu	Wroc?aw
Romania	Cardiomed Medical Center	Cluj-Napoca
Romania	Prof Dr I Chiricuta Institute of Oncology; Oncology Department	Cluj-napoca
Romania	Oncomed SRL; Oncologie	Timisoara
Russian Federation	GUZ Regional clinical hospital # 1	Krasnodar
Russian Federation	Moscow City Oncology Hospital #62	Moscovskaya Oblast	Moskovskaja Oblast
Russian Federation	FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF	Moscow	Moskovskaja Oblast
Russian Federation	P.A. Gertsen Cancer Research Inst. ; Chemotherapy Dept	Moscow	Moskovskaja Oblast
Russian Federation	SPb City Clin Onc Dsp; Chemotherapy	Sankt-peterburg	Sankt Petersburg
Russian Federation	Pavlov First Saint Petersburg State Medical University	St. Petersburg	Sankt Petersburg
Russian Federation	Scientific Research Oncology Institute named after N.N. Petrov; Oncology	St. Petersburg	Sankt Petersburg
Spain	Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia	Badalona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona
Spain	Hospital Universitari Dexeus - Grupo Quironsalud; Servicio de Oncologia Medica	Barcelona
Spain	Hospital Universitari Vall d'Hebron; Oncology	Barcelona
Spain	Hospital Universitario Donostia: Oncology Service	Donostia-san Sebastian	Guipuzcoa
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología	La Coruña
Spain	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Puerta de Hierro; Servicio de Oncologia	Majadahonda	Madrid
Spain	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
Spain	Hospital Universitari i Politecnic La Fe; Oncologia	Valencia
Taiwan	Chang Gung Memorial Foundation - Kaohsiung	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Chang Gung Medical Foundation - Linkou; Chest Dept	Taoyuan
Taiwan	Taichung Veterans General Hospital	Xitun Dist.
Thailand	Chulalongkorn Hospital; Medical Oncology	Bangkok
Thailand	Ramathibodi Hospital; Medicine/Oncology	Bangkok
Thailand	Siriraj Hospital; Medical Oncology Unit	Bangkok
Turkey	Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology	Adana
Turkey	Ankara Ataturk Chest Diseases Training and Research Hospital	Ankara
Turkey	Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology	Istanbul
Turkey	Ege Uni Medical Faculty Hospital; Oncology Dept	Izmir
Turkey	Izmir Suat Seren Chest Diseases and Surgery Research Hospital	Izmir
Turkey	Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department	Malatya
Turkey	Medikal Park Samsun	Samsun
Turkey	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye/Ankara
Ukraine	Chemotherapy SI Dnipropetrovsk MA of MOHU	Dnipropetrovsk
Ukraine	Medical center of Yuriy Spizhenko LLC	Kapitanovka Village	KIEV Governorate
Ukraine	Kyiv City Clinical Oncological Center	Kyiv
Ukraine	RCI Sumy Regional Clinical Oncological Dispensary	Sumy
Ukraine	Vinnytsia Regional Clinical Oncology Dispensary; Department of Chemotherapy	Vinnytsia
United Kingdom	Guys Hospital; Guys Cancer Center	London
United Kingdom	St Bartholomew's Hospital	London
United Kingdom	Wythenshaw Hospital	Manchester
United States	MGH Cancer Center	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belarus,  Bosnia and Herzegovina,  China,  Denmark,  Egypt,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Japan,  Kazakhstan,  Korea, Republic of,  North Macedonia,  Poland,  Romania,  Russian Federation,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival (DFS), as Assessed by the Investigator	DFS, defined as the time from randomization to the first documented recurrence of disease or new primary NSCLC as determined by the investigator through use of an integrated assessment of radiographic data, biopsy sample results (if clinically feasible), and clinical status or death from any cause, whichever occurs first	From the date of randomization until the first DFS event, up to approximately 5 years
Secondary	Overall Survival (OS)	Primary OS analysis at approximately 5 years after FPI and final OS analysis at approximately 8 years after FPI.; OS, defined as the time from randomization to death from any cause.	From the date of randomization until death due to any cause up to approximately 8 years
Secondary	Plasma Concentration of Alectinib		Predose (2 hours) at Baseline, Week 3, 6, 9, 12, 24, 36, 48, 60, 72, 84, and 96
Secondary	Plasma Concentration of Alectinib metabolite		Predose (2 hours) at Baseline, Week 3, 6, 9, 12, 24, 36, 48, 60, 72, 84, and 96
Secondary	Percentage of Participants with Adverse Advent	Incidence of Adverse Events, with Severity Determined Through Use of National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 Safety Laboratory Values, Vital Signs, ECG	From the date of randomization up to approximately 2 years