Alectinib Versus Pemetrexed or Docetaxel in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small Cell Lung Cancer (NSCLC) Participants Previously Treated With Platinum-Based Chemotherapy and Crizotinib

Non-small Cell Lung Cancer Clinical Trial

Official title:

Randomized, Multicenter, Phase III, Open-Label Study of Alectinib Versus Pemetrexed or Docetaxel in Anaplastic Lymphoma Kinase-Positive Advanced Non Small Cell Lung Cancer Patients Previously Treated With Platinum-Based Chemotherapy and Crizotinib

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02604342
• Other study ID #: MO29750
• Secondary ID: 2015-000634-29
• Status: Completed
• Phase: Phase 3
• Start date: November 3, 2015
• Est. completion date: August 13, 2018

Study information

• Verified date: October 2019
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized active-controlled multicenter Phase III open-label study will evaluate and compare between treatment groups the efficacy of alectinib versus chemotherapy in participants with ALK-positive advanced NSCLC who were previously treated with chemotherapy and crizotinib, as measured by investigator-assessed progression-free survival (PFS) and to evaluate and compare between treatment groups the central nervous system (CNS) objective response rate (C-ORR) in participants with measurable CNS metastases at baseline, as assessed by an Independent Review Committee (IRC).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: August 13, 2018
• Est. primary completion date: January 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive. ALK positivity must have been determined by a validated fluorescence in situ hybridization (FISH) test (recommended probe, Vysis ALK Break-Apart Probe) or a validated immunohistochemistry (IHC) test (recommended antibody, clone D5F3)

• Participant had received two prior systemic lines of therapy, which must have included one line of platinum-based chemotherapy and one line of crizotinib

• Prior CNS or leptomeningeal metastases allowed if asymptomatic

• Participants with symptomatic CNS metastases for whom radiotherapy is not an option will be allowed to participate in this study

• Measurable disease by RECIST Version 1.1 prior to the administration of study treatment

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• For all females of childbearing potential, a negative pregnancy test must be obtained within 3 days before starting study treatment

Exclusion Criteria:

• Participants with a previous malignancy within the past 3 years are excluded (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal [GI] cancer by endoscopic resection or in situ carcinoma of the cervix)

• Participants who have received any previous ALK inhibitor other than crizotinib

• Any GI disorder that may affect absorption of oral medications

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Alectinib
Participants will receive oral alectinib at a dose of 600 mg twice daily, taken with food until disease progression, unacceptable toxicity, withdrawal of consent or death.
• Docetaxel
Participants will receive docetaxel at a dose of 75 mg/m^2 of body surface area intravenously every 3 weeks, until disease progression, unacceptable toxicity, withdrawal of consent or death.
• Pemetrexed
Participants will receive pemetrexed at a dose of 500 mg/m^2 of body surface area intravenously every 3 weeks, until disease progression, unacceptable toxicity, withdrawal of consent or death.

Locations

Country	Name	City	State
Belgium	GHdC Site Notre Dame	Charleroi
Belgium	UZ Antwerpen	Edegem
Belgium	UZ Gent	Gent
Bulgaria	MBAL Serdika EOOD	Sofia
France	Centre Francois Baclesse	Caen
France	Hopital Bichat Claude Bernard ; Service de Pneumologie	Paris
France	Hopital Du Haut Leveque; Service Des Maladies Respiratoires	Pessac
France	Hopital Foch; Pneumologie	Suresnes
France	Hopital Sainte Musse; Pneumologie	Toulon
France	Hopital Larrey; Pneumologie	Toulouse
France	Hopital Robert Schuman; Pneumologie	Vantoux
Germany	Zentralklinik Bad Berka GmbH; Abteilung Onkologie und Hämatologie	Bad Berka
Germany	Evang. Lungenklinik Berlin Klinik für Pneumologie	Berlin
Germany	Asklepios-Fachkliniken Muenchen-Gauting; Onkologie	Gauting
Germany	Fachklinik für Lungenerkrankungen	Immenhausen
Germany	Pius-Hospital; Klinik fuer Haematologie und Onkologie	Oldenburg
Hong Kong	Queen Elizabeth Hospital; Clinical Oncology	Hong Kong
Hong Kong	Queen Mary Hospital; Dept. of Clinical Oncology	Hong Kong
Hungary	Semmelweis Egyetem X; Pulmonologiai Klinika	Budapest
Italy	Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati	Avellino	Campania
Italy	POLICLINICO RODOLICO, U.O. di Oncologia Medica	Catania	Sicilia
Italy	Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica	Milano	Lombardia
Italy	Irccs Ospedale San Raffaele;Oncologia Medica	Milano	Lombardia
Italy	AORN Ospedali dei Colli Ospedale Monaldi; UOC Pneumologia ad indirizzo Oncologico	Napoli	Campania
Italy	Istituto Nazionale Tumori Fondazione G. Pascale; U.O.C. Oncologia Medica Toraco Polmonare	Napoli	Campania
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; U.O.C. Pneumologia Ad Indirizzo Oncologico 1	Roma	Lazio
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollanam-do
Korea, Republic of	Korea University Guro Hospital; Oncology	Seoul
Norway	Oslo Universitetssykehus HF; Radiumhospitalet	Oslo
Poland	Medical University of Gdansk	Gdansk
Portugal	Hospital Geral; Servico de Pneumologia	Coimbra
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Portugal	CHVNG/E_Unidade 1; Servico de Pneumologia	Vila Nova De Gaia
Russian Federation	City Clinical Oncology Hospital	Moscow
Russian Federation	Main Military Clinical Hospital named after N.N. Burdenko	Moscow
Russian Federation	University ?linic of headaches	Moscow	Moskovskaja Oblast
Russian Federation	City Clinical Oncology Dispensary	Saint-Petersburg
Russian Federation	S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)	Saint-Petersburg
Russian Federation	FSBI"National Medical Research Center of Oncology named after N.N.Petrov" MHRF	St Petersburg	Leningrad
Slovakia	FNsP F. D. Roosevelta Banska Bystrica, II.Ocna klinika SZU	Banska Bystrica
Slovakia	Vychodoslovensky onkologicky ustav	Košice
Spain	Hospital de Cruces; Servicio de Oncologia	Bilbao	Vizcaya
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Hospital Universitario de Torrejon	Torrejon de Ardoz	Madrid
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Turkey	Adana Acibadem Hospital Oncology Department	Adana
Turkey	Hacettepe Uni Medical Faculty Hospital; Oncology Dept	Ankara
Turkey	Istanbul Uni Capa Medical Faculty; Inst. of Oncology	Istanbul
Turkey	Ege University Medical Faculty; Chest Diseases	Izmir
Turkey	Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department	Malatya

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Belgium,  Bulgaria,  France,  Germany,  Hong Kong,  Hungary,  Italy,  Korea, Republic of,  Norway,  Poland,  Portugal,  Russian Federation,  Slovakia,  Spain,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator	PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.	Randomization to first documented disease progression, death from any cause, or study end (up to 33 months)
Secondary	Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC	Overall response rate in subjects with confirmed CNS response (C-ORR) was defined as the percentage of subjects who attained Complete Response (CR) or Partial Response (PR) for lesions in the CNS. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.	Baseline through study end (up to 33 months)
Secondary	PFS Using RECIST Version 1.1 as Assessed by IRC	PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions.; This outcome measure was assessed as part of the primary analysis and was not repeated during final analysis.	Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Secondary	Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC	ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.; The IRC assessment was part of the primary analysis and was not repeated during final analysis.	Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Secondary	Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC	Disease control rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started.; The IRC assessment was part of the primary analysis and was not repeated during final analysis.	Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Secondary	Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC	DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. DOR was evaluated for participants who had a best overall response (BOR) of CR or PR.; The IRC assessment was part of the primary analysis and was not repeated during final analysis.	From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)
Secondary	PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC	PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions.; This outcome measure assessment was part of the primary analysis and was not repeated during final analysis.	Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Secondary	Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC	Time to CNS progression was defined as the time from randomization until radiographic evidence of CNS progression. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions.; This outcome measure assessment was part of the primary analysis and was not repeated during final analysis.	Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Secondary	Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC	Disease Control Rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started.	From first documented CR, PR, or SD lasting at least 5 weeks through study end (up to 33 months)
Secondary	Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC	ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.	Baseline through study end (up to 33 months)
Secondary	Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC	DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. C-DOR was defined in a similar way for lesions in the CNS, taking into account all lesions in the body. DOR was evaluated for participants who had a BOR of CR or PR.	From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)
Secondary	Overall Survival (OS)	Overall survival (OS) was defined as the time from randomization to death from any cause. OS was confounded by cross-over of participants to the alectinib arm.	Randomization to death from any cause, through study end (up to 33 months)
Secondary	Plasma Concentration of Alectinib		Predose (2 hours) at Baseline, Week 3 and Week 6
Secondary	Plasma Concentration of Alectinib Metabolite		Predose (2 hours) at Baseline, Week 3 and Week 6
Secondary	Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time	Percentage of participants who filled out an EORTC QLQ-C30 questionnaire at a visit. The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden.	Baseline through Week 138
Secondary	Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time	Percentage of participants who filled out an EORTC QLQ-LC13 questionnaire at a visit. The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis.	Baseline through Week 138
Secondary	Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time	Percentage of participants who filled out an ED-5D-5L questionnaire at a visit. EQ-5D-5L: A generic preference-based health utility measure that provides a single index value for health status. The instrument consists of two parts. The first part, health-state classification, contains five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.	Baseline through Week 60
Secondary	Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population	TTD in the overall population is defined as time from randomization to the earliest time with a =10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13.	Baseline through study end (up to 33 months)
Secondary	Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population	TTD in the overall population is defined as time from randomization to the earliest time with a =10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13.	Baseline through study end (up to 33 months)
Secondary	Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population	TTD in the overall population is defined as time from randomization to the earliest time with a =10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30.	Baseline through study end (up to 33 months)
Secondary	Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population	TTD in the overall population is defined as time from randomization to the earliest time with a =10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30.	Baseline through study end (up to 33 months)
Secondary	TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population	TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a =10-point increase from baseline for any component of the composite of the three following symptoms [cough, dyspnea [multi-item subscales QLQ-LC13] and chest pain]) as measured by the EORTC QLQ-LC13.	Baseline through study end (up to 33 months)
Secondary	TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population	TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a =10-point increase from baseline for any component of the composite of the three following symptoms [cough, dyspnea [multi-item subscales QLQ-LC13] and chest pain]) as measured by the EORTC QLQ-LC13.	Baseline through study end (up to 33 months)
Secondary	Percentage of Participants With Adverse Events (AEs)	An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Baseline through study end (up to 33 months)