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

Roche

Status and phase: Completed; Phase 3

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: Docetaxel; Drug: Pemetrexed; Drug: Alectinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02604342

2015-000634-29 (EudraCT Number)

MO29750

Details and patient eligibility

About

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).

Enrollment: 119 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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119 participants in 2 patient groups

Alectinib

Experimental group

Description:

Participants will receive oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food until disease progression, unacceptable toxicity, withdrawal of consent or death.

Treatment:

Drug: Alectinib

Premetrexed/Docetaxel

Active Comparator group

Description:

Participants will receive chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.

Treatment:

Drug: Pemetrexed

Drug: Docetaxel