A Phase III, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Adjuvant Alectinib Versus Adjuvant Platinum-Based Chemotherapy in Patients With Completely Resected Stage IB (Tumors Equal to or Larger Than 4cm) to Stage IIIA Anaplastic Lymphoma Kinase Positive Non-Small Cell Lung Cancer

Hoffmann-La Roche114 sites in 15 countries257 target enrollmentAugust 16, 2018

InterventionsAlectnib Cisplatin Vinorelbine Gemcitabine Pemetrexed Carboplatin

Overview

Phase: Phase 3
Intervention: Alectnib
Conditions: Not specified
Sponsor: Hoffmann-La Roche
Enrollment: 257
Locations: 114
Primary Endpoint: Disease-free Survival (DFS), as Assessed by the Investigator
Status: Active, not recruiting
Last Updated: 3 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

August 16, 2018

End Date

November 19, 2026

Last Updated

3 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

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

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

Arms & Interventions

Alectinib

Intervention: Alectnib

Platinum-Based Chemotherapy

Intervention: Cisplatin

Platinum-Based Chemotherapy

Intervention: Vinorelbine

Platinum-Based Chemotherapy

Intervention: Gemcitabine

Platinum-Based Chemotherapy

Intervention: Pemetrexed

Platinum-Based Chemotherapy

Intervention: Carboplatin

Outcomes

Primary Outcomes

Disease-free Survival (DFS), as Assessed by the Investigator

Time Frame: Approximately 58 months

DFS, defined as the time from randomization to the first documented recurrence of disease or new primary NSCLC as determined by the investigator through use of an integrated assessment of radiographic data, biopsy sample results (if clinically feasible), and clinical status or death from any cause, whichever occurs first

Secondary Outcomes

Overall Survival (OS)(From the date of randomization until death due to any cause up to approximately 8 years)
Percentage of Participants With Adverse Events (AEs)(Until 28 days after the last dose of alectinib (up to 2 years) or 28 days after end of last cycle of chemotherapy (up to 4 cycles))
AEs Grade 3-5 With a Difference in Incidence Rate of at Least 2% Between Treatment Arms(Until 28 days after the last dose of alectinib (up to 2 years) or 28 days after end of last cycle of chemotherapy (up to 4 cycles))
Plasma Concentration of Alectinib(Predose (2 hours) Week 3 - Week 96)
Plasma Concentration of Alectinib Metabolite M4(Predose (2 hours) Week 3 - Week 96)