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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Alectnib
* Drug: Cisplatin
* Drug: Vinorelbine
* Drug: Gemcitabine
* Drug: Pemetrexed
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alectinib<br> | Drug: Alectnib<br>* Participants will receive alectinib 600 mg orally BID until completion of treatment period (24 months) or recurrence of disease , unacceptable toxicity, withdrawal of consent or death, whichever occurs first.<br>* Other names: RO5424802;|
| Active Comparator: Platinum-Based Chemotherapy<br> | Drug: Cisplatin<br>* Participants will receive Cisplatin 75 milligrams per square meter (mg/m^2) on Day 1 every 21 days IV intravenously (IV) until completion of treatment period (4 cycles), recurrence of disease, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first.<br>Drug: Vinorelbine<br>* Participants will receive Vinorelbine 25 mg/m^2 IV on Days 1 and 8 Q21D until completion of treatment period (4 cycles), recurrence of disease, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first.<br>* Other names: Navelbine;Drug: Gemcitabine<br>* Participants will receive Gemcitabine 1250 mg/m^2 on Days 1 and 8 Q21D IV until completion of treatment period (4 cycles), recurrence of disease, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first.<br>* Other names: Gitrabin;Drug: Pemetrexed<br>* Participants will receive 500 mg/m^2 Day 1 Q21D until completion of treatment period (4 cycles), recurrence of disease, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first.<br>* Other names: Alimta®;Drug: Carboplatin<br>* For participants who experience unacceptable toxicity with cisplatin, carboplatin can be used.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free Survival (DFS), as Assessed by the Investigator | 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 | From the date of randomization until the first DFS event, up to approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Primary OS analysis at approximately 5 years after FPI and final OS analysis at approximately 8 years after FPI. OS, defined as the time from randomization to death from any cause. | From the date of randomization until death due to any cause up to approximately 8 years | 
| Plasma Concentration of Alectinib |  | Predose (2 hours) at Baseline, Week 3, 6, 9, 12, 24, 36, 48, 60, 72, 84, and 96 | 
| Plasma Concentration of Alectinib metabolite |  | Predose (2 hours) at Baseline, Week 3, 6, 9, 12, 24, 36, 48, 60, 72, 84, and 96 | 
| Percentage of Participants with Adverse Advent | Incidence of Adverse Events, with Severity Determined Through Use of National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 Safety Laboratory Values, Vital Signs, ECG | From the date of randomization up to approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, alectinib, ALK positive,adjuvant treatment, platinum based chemotherapy, complete resection, Stage IB-IIIA.