Clinical Trials Register

Summary
EudraCT Number:	2013-004133-33
Sponsor's Protocol Code Number:	BO28984
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2014-06-10
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Poland - Office for Medicinal Products

A.2

EudraCT number

2013-004133-33

A.3

Full title of the trial

RANDOMIZED, MULTICENTER, PHASE III, OPEN LABEL STUDY OF ALECTINIB VERSUS CRIZOTINIB IN TREATMENT NAÏVE ANAPLASTIC LYMPHOMA KINASE-POSITIVE ADVANCED NON-SMALL CELL LUNG CANCER

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Alectinib versus crizotinib in previously untreated patients with advanced ALK-positive non-small cell lung cancer.

A.4.1

Sponsor's protocol code number

BO28984

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1160-7882

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	F. Hoffmann-La Roche Ltd
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	F. Hoffmann-La Roche Ltd
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	F. Hoffmann-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.6	E-mail	global.rochegenentechtrials@roche.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Alectinib
D.3.2	Product code	RO5424802
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Alectinib
D.3.9.2	Current sponsor code	Ro542-4802/F03
D.3.9.3	Other descriptive name	ALK INHIBITOR
D.3.9.4	EV Substance Code	SUB117669
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Xalkori
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Crizotinib
D.3.9.1	CAS number	877399-52-5
D.3.9.3	Other descriptive name	Crizotinib
D.3.9.4	EV Substance Code	SUB32267
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	250
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Xalkori
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Crizotinib
D.3.9.1	CAS number	877399-52-5
D.3.9.3	Other descriptive name	Crizotinib
D.3.9.4	EV Substance Code	SUB32267
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer
(NSCLC)

E.1.1.1

Medical condition in easily understood language

Alectinib versus crizotinib in previously untreated patients with advanced ALK positive NSCLC

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Investigator assessed progression-free survival (PFS)

E.2.2

Secondary objectives of the trial

PFS by the independent review committee (IRC); time to CNS progression by IRC; Objective Response Rate (ORR) and Duration of Response (DOR); time to deterioration (TTD) in patient-reported lung cancer symptoms; health-related quality of life (HRQoL); safety and tolerability; pharmacokinetics of alectinib and metabolite(s); overall survival (OS).

E.2.3

Trial contains a sub-study

E.3

Principal 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 as assessed by the Ventana IHC test. Sufficient tumor tissue to perform ALK IHC and ALK FISH is required. Both tests will be performed at designated central laboratories.
•Measurable disease (by RECIST v1.1) prior to the administration of study treatment.
•Patients had no prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC.
•ECOG PS of 0 2.
•Adequate hematologic, renal and liver function.
•Patients must have recovered from effects of any major surgery or significant traumatic injury at least 28 days before the first dose of study
treatment.
•Prior brain or leptomeningeal metastases allowed if asymptomatic (e.g., diagnosed incidentally at study baseline). Asymptomatic CNS
lesions might be treated at the discretion of the investigator as per local clinical practice. If patients have neurological symptoms or signs due to CNS metastasis, patients need to complete whole brain radiation or gamma knife irradiation treatment. In all cases, radiation treatment must be completed at least 14 days before enrollment and patients must be clinically stable.
•Able and willing to provide written informed consent prior to performing any study related procedures and to comply with the study protocol.

E.4

Principal exclusion criteria

•Patients 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, in situ carcinoma of the cervix, or any cured cancer that is considered to have no impact in PFS and OS for the current NSCLC).
•Any gastrointestinal (GI) disorder that may affect absorption of oral medications, such as mal-absorption syndrome or status post-major bowel resection.
•National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) Grade 3 or higher toxicities due to any prior therapy such as radiotherapy (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication
•Co-administration of anti-cancer therapies other than those administered in this study
•Liver disease characterized by:
ALT or AST > 3 × upper limit of normal (ULN; ≥ 5 × ULN for patients with concurrent liver metastasis) confirmed on two consecutive measurements OR
Impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as
coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices OR Acute viral or active autoimmune, alcoholic, or other types of acute hepatitis
•Patients with baseline QTc > 470 milliseconds (ms) or symptomatic bradycardia
•Administration of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment with alectinib or crizotinib
•Administration of agents with potential QT interval prolonging effects within 14 days prior to the first administration of study drugfor all
patients and while on treatment through the end of the study for crizotinib-treated patients only.
•History of organ transplant
•Pregnant or lactating women
•Known HIV positivity or AIDS-related illness
•History of hypersensitivity to any of the additives in the alectinib drug formulation
•History of hypersensitivity to any of the additives in the crizotinib drug formulation
•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, in the opinion of the Principal Investigator, pose an unacceptable risk to the patient in this study.

E.5 End points

E.5.1

Primary end point(s)

PFS, as assessed by investigator

E.5.1.1

Timepoint(s) of evaluation of this end point

The time from date of randomization to the date of first documented disease progression (as per RECIST 1.1) or death, whichever occurs first

E.5.2

Secondary end point(s)

1 PFS by IRC
2 Time to CNS Progression by IRC
3 ORR
4 DOR
5 Time to deterioration (TTD) in patient-reported lung cancer symptoms
6 Health-related quality of life (HRQoL)
7 Safety and tolerability
8 Pharmacokinetics of alectinib and metabolite(s)
9 Overall survival (OS)

E.5.2.1

Timepoint(s) of evaluation of this end point

1 The same methodology as specified for PFS
2 The time from randomization until radiographic evidence of CNS
progression
3 The percentage of patients who attain a CR or PR (as per RECIST 1.1)
4. The time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first)
5-6 From baseline until disease progression and during post-progression on treatment in case of isolated, asymptomatic CNS progression; at the post-treatment visit (4 weeks after permanent treatment discontinuation); and at survival follow-up for 6 months
7 Throughout the study
8 Until disease progression
9 The time from the date of randomization to the date of death due to
any cause

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Chile

Costa Rica

Dominican Republic

Egypt

Guatemala

New Zealand

Peru

Singapore

Switzerland

Bosnia and Herzegovina

Ukraine

Hong Kong

Taiwan

Australia

Brazil

Canada

China

Israel

Korea, Republic of

Mexico

Russian Federation

Serbia

Thailand

United Kingdom

Bulgaria

Czechia

Denmark

France

Germany

Greece

Hungary

Italy

Poland

Portugal

Romania

Spain

Türkiye

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

This study is event-driven, with a recruitment period of approximately 18 months.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

233

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

303

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

At the discretion of the investigator according to the local clinical
practice.
The Sponsor will offer post-trial access to the study drug alectinib free
of charge to eligible patients in accordance with the Roche Global
Policy on Continued Access to Investigational Medicinal Product, as
outlined in the Protocol Section 4.3.4.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-07-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-06-26

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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