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

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03456076

Collaborator

(none)

257

Enrollment

141

Locations

Arms

99.1

Anticipated Duration (Months)

1.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Alectnib Drug: Cisplatin Drug: Vinorelbine Drug: Gemcitabine Drug: Pemetrexed Drug: Carboplatin	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

257 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 16, 2018

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Nov 19, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alectinib	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. Other Names: RO5424802
Active Comparator: Platinum-Based Chemotherapy	Drug: 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." Drug: 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. Other Names: Navelbine Drug: 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. Other Names: Gitrabin Drug: 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." Other Names: Alimta® Drug: Carboplatin For participants who experience unacceptable toxicity with cisplatin, carboplatin can be used.

Arm

Intervention/Treatment

Experimental: Alectinib

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.

Other Names:

RO5424802

Active Comparator: Platinum-Based Chemotherapy

Drug: 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."

Drug: 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.

Other Names:

Navelbine

Drug: 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.

Other Names:

Gitrabin

Drug: 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."

Other Names:

Alimta®

Drug: Carboplatin

For participants who experience unacceptable toxicity with cisplatin, carboplatin can be used.

Outcome Measures

Primary Outcome Measures

Disease-free Survival (DFS), as Assessed by the Investigator [From the date of randomization until the first DFS event, up to approximately 5 years]
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

Secondary Outcome Measures

Overall Survival (OS) [From the date of randomization until death due to any cause up to approximately 8 years]
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.
Plasma Concentration of Alectinib [Predose (2 hours) at Baseline, Week 3, 6, 9, 12, 24, 36, 48, 60, 72, 84, and 96]
Plasma Concentration of Alectinib metabolite [Predose (2 hours) at Baseline, Week 3, 6, 9, 12, 24, 36, 48, 60, 72, 84, and 96]
Percentage of Participants with Adverse Advent [From the date of randomization up to approximately 2 years]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rush University Medical Center	Chicago	Illinois	United States	60612
2	MGH Cancer Center	Boston	Massachusetts	United States	02114
3	Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
4	Chris O'Brien Lifehouse	Camperdown	New South Wales	Australia	2050
5	Northern Cancer Institute	St Leonards	New South Wales	Australia	2065
6	Cairns Base Hospital; Cancer Care Centre	Cairns	Queensland	Australia	4870
7	Townsville Hospital	Townsville	Queensland	Australia	4810
8	Peter MacCallum Cancer Center	North Melbourne	Victoria	Australia	3051
9	Krankenhaus Nord - Klinik Floridsdorf; Abteilung Pulmologie	Wien		Austria	1210
10	Healthcare Institution Grodno University Hospital; Regional Oncologic Dispensary	Grodno	Hrodzyenskaya Voblasts'	Belarus	230030
11	Healthcare Institution "Gomel Regional Clinical Oncologic Dispensary"	Gomel		Belarus	246012
12	Vitebsk Regional Clinical Oncology Dispensary	Vitebsk		Belarus	BU-210603
13	Clinic of Oncology, University Clinical Center Sarajevo	Sarajevo		Bosnia and Herzegovina	7100
14	Beijing Cancer Hospital	Beijing		China	100142
15	Jilin Cancer Hospital	Changchun		China	132013
16	West China Hospital, Sichuan University	Chengdu		China	610041
17	Fujian Medical University Union Hospital	Fuzhou City		China	350001
18	Guangdong General Hospital	Guangzhou		China	510080
19	Shandong Cancer Hospital	Jinan		China	250117
20	Shanghai Chest Hospital	Shanghai		China	200000
21	Zhongshan Hospital Fudan University	Shanghai		China	200032
22	Shenzhen People's Hospital	Shenzhen		China	510852
23	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City		China	430023
24	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an		China	710061
25	Zhejiang Cancer Hospital	Zhejiang		China	310022
26	Odense Universitetshospital, Onkologisk Afdeling R	Odense C		Denmark	5000
27	Kasr Eieny Uni Hospital; Oncology (Nemrock)	Cairo		Egypt	11555
28	National Cancer Institute	Cairo		Egypt	11796
29	CHU Angers	Angers		France	49933
30	Hopital Nord AP-HM	Marseille		France	13015
31	Hôpital Arnaud de Villeneuve	Montpellier		France	34295
32	Hopital Bichat Claude Bernard; Oncologie Serv.	Paris		France	75018
33	Ch De Saint Quentin; Medecine B14	St Quentin		France	02321
34	Hôpital d'Instruction des Armées de Sainte Anne; Service de Pneumologie	Toulon		France	83000
35	Institut Gustave Roussy; Pathologie Thoracique	Villejuif cedex		France	94805
36	Klinikum Chemnitz gGmbH	Chemnitz		Germany	09116
37	Niels-Stensen-Kliniken Franziskus-Hospital Harderberg GmbH	Georgsmarienhütte		Germany	49124
38	Thoraxklinik Heidelberg gGmbH	Heidelberg		Germany	69126
39	Fachklinik für Lungenerkrankungen	Immenhausen		Germany	34376
40	Metropolitan Hospital	Athens		Greece	185 47
41	Theageneio Hospital	Thessaloniki		Greece	54007
42	Semmelweis Egyetem, AOK, Pulmonologiai Klinika	Budapest		Hungary	1083
43	Orszagos Onkologiai Intezet	Budapest		Hungary	1122
44	University of Pecs; 1St Department of Medicine	Pecs		Hungary	7623
45	Hetenyi Geza County Hospital; Onkologiai Kozpont	Szolnok		Hungary	5004
46	Rambam Health Care Campus; Oncology	Haifa		Israel	3109601
47	Meir Medical Center	Kfar- Saba		Israel	4428164
48	Az. Osp. Monaldi; 1 Pneumologia Oncologica	Napoli	Campania	Italy	80131
49	Azienda Osp. Univ di Modena; Dept Onc & Hem	Modena	Emilia-Romagna	Italy	41100
50	Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica	Ravenna	Emilia-Romagna	Italy	48100
51	Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica	Aviano	Friuli-Venezia Giulia	Italy	33081
52	Azienda Ospedaliera San Camillo Forlanini - Unità Operativa Complessa di Pneumologia Oncologica 1	Roma	Lazio	Italy	00151
53	A.O. Istituti Ospitalieri - Cremona; S.C. Oncologia	Cremona	Lombardia	Italy	26100
54	Irccs Ospedale San Raffaele;Oncologia Medica	Milano	Lombardia	Italy	20132
55	Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia	Milano	Lombardia	Italy	20141
56	Az. Osp. S. Luigi Gonzaga; Malattie Apparato Respiratorio 5 Ad Indirizzo Oncologico	Orbassano	Piemonte	Italy	10043
57	A.O. Universitaria Pisana-Ospedale Cisanello; Dipartimento Cardio Toracico-Pneumologia Ii	Pisa	Toscana	Italy	56124
58	Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica	Perugia	Umbria	Italy	06156
59	Aichi Cancer Center	Aichi		Japan	464-8681
60	National Cancer Center Hospital East	Chiba		Japan	277-8577
61	National Hospital Organization Kyushu Cancer Center	Fukuoka		Japan	811-1395
62	Hiroshima University Hospital	Hiroshima		Japan	734-8551
63	National Hospital Organization Hokkaido Cancer Center	Hokkaido		Japan	003-0804
64	National Hospital Organization Himeji Medical Center	Hyogo		Japan	670-8520
65	Kanagawa Cancer Center	Kanagawa		Japan	241-8515
66	Kumamoto University Hospital	Kumamoto		Japan	860-8556
67	Kyoto University Hospital	Kyoto		Japan	606-8507
68	Sendai Kousei Hospital	Miyagi		Japan	980-0873
69	Niigata Cancer Center Hospital	Niigata		Japan	951-8566
70	Okayama University Hospital	Okayama		Japan	700-8558
71	Osaka City General Hospital	Osaka		Japan	534-0021
72	Shizuoka Cancer Center	Shizuoka		Japan	411-8777
73	National Cancer Center Hospital	Tokyo		Japan	104-0045
74	Juntendo University Hospital	Tokyo		Japan	113-8431
75	The Cancer Institute Hospital of JFCR	Tokyo		Japan	135-8550
76	Tokyo Medical University Hospital	Tokyo		Japan	160-0023
77	Almaty Cancer Hospital; Chemotherapy department	Almaty		Kazakhstan	050054
78	National Cancer Center	Goyang-si		Korea, Republic of	10408
79	Ajou University Medical Center	Gyeonggi-do		Korea, Republic of	16499
80	Gachon University Gil Medical Center	Incheon		Korea, Republic of	21565
81	Chonnam National University Hwasun Hospital	Jeollanam-do		Korea, Republic of	58128
82	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13605
83	Asan Medical Center	Seoul		Korea, Republic of	05505
84	Samsung Medical Center	Seoul		Korea, Republic of	06351
85	Korea University Guro Hospital	Seoul		Korea, Republic of	08308
86	PHI University Clinic of Radiotherapy and Oncology; Malignant diseases of thorax	Skopje		North Macedonia	1000
87	Private Health Organization Acibadem Sistina Hospital	Skopje		North Macedonia	1000
88	Gdanski Uniwersytet Medyczny; Katedra i Klinika Onkologii i Radioterapii	Gdańsk		Poland	80-214
89	Krakowski Szpital Specjalistyczny im. Jana Pawła II; Oddz. Klin. Chir. Klatki Piersiowej i Onkol.	Kraków		Poland	31-202
90	Warminsko-Mazurskie Centrum Chorób Płuc w Olsztynie; Oddzial onkologii z pododdzialem chemioterapii	Olsztyn		Poland	10-357
91	Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu	Poznan		Poland	60-569
92	Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad; Klinika Nowot.Pluca i Klatki Piers	Warszawa		Poland	02-781
93	Dolnoslaskie Centrum Chorob Pluc we Wroclawiu	Wrocław		Poland	53-439
94	Cardiomed Medical Center	Cluj-Napoca		Romania	400015
95	Prof Dr I Chiricuta Institute of Oncology; Oncology Department	Cluj-napoca		Romania	400015
96	Oncomed SRL; Oncologie	Timisoara		Romania	300239
97	Moscow City Oncology Hospital #62	Moscovskaya Oblast	Moskovskaja Oblast	Russian Federation	143423
98	GUZ Regional clinical hospital # 1	Krasnodar		Russian Federation	350086
99	FSBI Russian Oncology Research Center n.a. Blokhin of MOH RF	Moscow		Russian Federation	115478
100	P.A. Gertsen Cancer Research Inst. ; Chemotherapy Dept	Moscow		Russian Federation	125284
101	Pavlov First Saint Petersburg State Medical University	St. Petersburg		Russian Federation	197022
102	SPb City Clin Onc Dsp; Chemotherapy	St. Petersburg		Russian Federation	197022
103	Scientific Research Oncology Institute named after N.N. Petrov; Oncology	St. Petersburg		Russian Federation	197758
104	Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia	Badalona	Barcelona	Spain	08916
105	Hospital Universitario Donostia: Oncology Service	Donostia-san Sebastian	Guipuzcoa	Spain	20014
106	Hospital Universitario Puerta de Hierro; Servicio de Oncologia	Majadahonda	Madrid	Spain	28222
107	Hospital Universitari Dexeus - Grupo Quironsalud; Servicio de Oncologia Medica	Barcelona		Spain	08028
108	Hospital Universitari Vall d'Hebron; Oncology	Barcelona		Spain	08035
109	Hospital de la Santa Creu i Sant Pau; Servicio de Oncologia	Barcelona		Spain	08041
110	Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología	La Coruña		Spain	15006
111	Hospital Clinico San Carlos; Servicio de Oncologia	Madrid		Spain	28040
112	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid		Spain	28041
113	Hospital Universitario La Paz; Servicio de Oncologia	Madrid		Spain	28046
114	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga		Spain	29011
115	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla		Spain	41013
116	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia		Spain	46010
117	Hospital Universitari i Politecnic La Fe; Oncologia	Valencia		Spain	46026
118	Chang Gung Memorial Foundation - Kaohsiung	Kaohsiung		Taiwan	00833
119	China Medical University Hospital	Taichung		Taiwan	40447
120	National Taiwan University Hospital	Taipei		Taiwan	10002
121	Chang Gung Medical Foundation - Linkou; Chest Dept	Taoyuan		Taiwan	333
122	Taichung Veterans General Hospital	Xitun Dist.		Taiwan	40705
123	Chulalongkorn Hospital; Medical Oncology	Bangkok		Thailand	10330
124	Ramathibodi Hospital; Medicine/Oncology	Bangkok		Thailand	10400
125	Siriraj Hospital; Medical Oncology Unit	Bangkok		Thailand	10700
126	Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology	Adana		Turkey	01230
127	Ankara Ataturk Chest Diseases Training and Research Hospital	Ankara		Turkey	06500
128	Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology	Istanbul		Turkey	34300
129	Ege Uni Medical Faculty Hospital; Oncology Dept	Izmir		Turkey	35100
130	Izmir Suat Seren Chest Diseases and Surgery Research Hospital	Izmir		Turkey	35110
131	Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department	Malatya		Turkey	44280
132	Medikal Park Samsun	Samsun		Turkey	55200
133	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Sihhiye/Ankara		Turkey	06230
134	Medical Center "Adonis" LLC	Kapitanovka Village	KIEV Governorate	Ukraine	08112
135	Chemotherapy SI Dnipropetrovsk MA of MOHU	Dnipropetrovsk		Ukraine	49102
136	Kyiv City Clinical Oncological Center	Kyiv		Ukraine	03115
137	RCI Sumy Regional Clinical Oncological Dispensary	Sumy		Ukraine	40005
138	Vinnytsia Regional Clinical Oncology Dispensary; Department of Chemotherapy	Vinnytsia		Ukraine	21029
139	St Bartholomew's Hospital	London		United Kingdom	EC1M 6BQ
140	Guys Hospital; Guys Cancer Center	London		United Kingdom	SE1 9RT
141	Wythenshaw Hospital	Manchester		United Kingdom	M23 9QZ