A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants (ALEX)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

9 Sep 2014 → 9 Apr 2025

Decision date (initial)

2024-07-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-506859-13-00

EudraCT number

2013-004133-33

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Others

To evaluate and compare the efficacy of alectinib compared with crizotinib in patients with treatment-naive anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC), as measured by investigator-assessed progression-free survival (PFS)

Secondary objectives 8

1. To evaluate and compare the ORR and duration of response (DOR) of alectinib compared with crizotinib in patients with treatment-naive anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer by investigator
2. To evaluate and compare the time to progression in the CNS of alectinib compared with crizotinib in patients with treatment-naive anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer on the basis of Independent Review Committee (IRC) review of radiographs by RECIST v1.1 and Revised Assessment in Neuro Oncology (RANO) criteria, as well as: – To evaluate CNS ORR (C-ORR) in patients with CNS metastases who have measurable disease in the CNS at baseline – To assess CNS DOR (C-DOR) in patients who have a CNS OR – To assess CNS progression rates (C-PR) at 6, 12, 18, and 24 months on the basis of cumulative incidence
3. To evaluate and compare the PFS assessment by the IRC of alectinib compared with crizotinib in patients with treatment-naive anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer
4. To evaluate and compare the OS of alectinib compared with crizotinib in patients with treatment-naive anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer
5. To evaluate the safety and tolerability of alectinib compared with crizotinib in patients with treatment-naive anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer
6. To characterize the pharmacokinetics of alectinib and metabolite(s) in patients with treatment-naive anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer
7. To evaluate and compare time to deterioration (TTD) of alectinib compared with crizotinib in patients with treatment-naive anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer in patient-reported lung cancer symptoms
8. To evaluate and compare PROs of health-related quality of life (HRQoL), patient functioning, and side effects of treatment of alectinib compared with crizotinib in patients with treatment-naive anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer

Conditions and MedDRA coding

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

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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 immunohistochemistry (IHC) test. Sufficient tumor tissue to perform ALK IHC and ALK fluorescent in situ hybridization (FISH) is required. Both tests will be performed at designated central laboratories.
2. Measurable disease (by Response Evaluation Criteria In Solid Tumors [RECIST] v1.1) prior to the administration of study treatment
3. Patients had no prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2
5. Adequate hematologic, renal and liver function.
6. 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.

Exclusion criteria 6

1. 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).
2. Any gastrointestinal (GI) disorder that may affect absorption of oral medications, such as mal absorption syndrome or status post-major bowel resection
3. 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
4. Liver disease - ALT or AST > 3 x upper limit of normal OR - Impaired excretory function OR - Acute viral or active autoimmune alcoholic, or other types of acute hepatitis Patients with baseline QTc > 470 ms or symptomatic bradycardia
5. 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.
6. Administration of agents with potential QT interval prolonging effects within 14 days prior to the first administration of study drug for all patients and while on treatment through the end of the study for crizotinib-treated patients only

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. PFS, as assessed by investigator

Secondary endpoints 9

1. 1. PFS by IRC
2. 2. Time to CNS Progression by IRC
3. 3. ORR as determined by the investigators using RECIST v1.1.
4. 4. DOR
5. 5. Time to deterioration (TTD) in patient-reported lung cancer symptoms
6. 6. Health-related quality of life (HRQoL)
7. 7. Safety and tolerability
8. 8. Pharmacokinetics of alectinib and metabolite(s)
9. 9. Overall survival (OS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 3

Locations

4 EU/EEA countries · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 33 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications