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

Roche

Status and phase: Active, not recruiting; Phase 3

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Carboplatin; Drug: Cisplatin; Drug: Vinorelbine; Drug: Pemetrexed; Drug: Alectnib; Drug: Gemcitabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT03456076

BO40336

2017-004331-37 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 257 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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257 participants in 2 patient groups

Alectinib

Experimental group

Treatment:

Drug: Alectnib

Platinum-Based Chemotherapy

Active Comparator group

Treatment:

Drug: Gemcitabine

Drug: Pemetrexed

Drug: Vinorelbine

Drug: Cisplatin

Drug: Carboplatin