The study population will consist of patients who have undergone complete resection with negative margins (R0) of histologically confirmed Stage IB (tumors equal to or larger than 4 cm) to Stage IIIA NSCLC as per UICC/AJCC, 7th edition. Patients will be randomized to receive either alectinib or platinum-based chemotherapy.
Conditions
Interventions
This study has three parts: 1) Screening 2) Treatment 3) Follow-up
The patient will be randomly placed in one of the following groups:
•One group will receive alectinib, (given as 4 capsules by mouth
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: •Signed Informed Consent Form •Age equal to and larger than 18 at time of signing Informed Consent Form •Complete resection of histologically confirmed Stage IB (tumor equal to and larger than 4 cm) to Stage IIIA (T2-3 N0, T1-3 N1, T1-3 N2, T4 N0 -1) NSCLC as per UICC/AJCC, 7th edition, with negative margins, at 4-12 weeks before enrollment Accepted types of resection include any of the following: lobectomy, sleeve lobectomy, bilobectomy, or pneumonectomy. Resection by segmentectomy or wedge resection is not allowed. N3 disease is not allowed. •If mediastinoscopy was not performed preoperatively, it is expected that, at a minimum, mediastinal lymph node systematic sampling will have occurred. Systematic sampling is defined as removal of at least one representative lymph node at specified levels. Complete mediastinal lymph node dissection (MLND) is preferred. MLND entails resection of all lymph nodes at those same levels. For patients who have undergone a right thoracotomy, sampling or MLND is required at Levels 4 and 7; for those who have undergone a left thoracotomy, sampling or MLND is required at Levels 5 and/or 6 and 7. Exceptions will be granted for the following situations: If patients have documented N2 disease in one level (per the UICC/AJCC staging system, 7th edition), not all levels need to be sampled. If the preoperative staging imaging results (contrast computed tomography [CT] and positron emission tomography scans) do not suggest evidence of disease in the mediastinum, the patient may be considered eligible even if N2 nodal sampling was not performed per surgeon’s decision. •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 (ECOG) Performance Status of Grade 0 or 1 •Adequate hematologic function, defined by the following laboratory test results, obtained within 3 days prior to initiation of study treatment: Platelet count 100 109/L ANC 1500/L Hemoglobin 9 g/dL •Adequate renal function, defined by the following laboratory test results, obtained within 3 days prior to initiation of study treatment: Serum creatinine 1.5 upper limit of normal (ULN) and Creatinine clearance (CrCl) 60 mL/min •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) 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 A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state ( 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). Examples of contraceptive methods with a failure rate of 1% per year include bilateral tubal ligation, male sterilization contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Hormonal contraceptive methods must be supplemented by a barrier method. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usu
Exclusion criteria
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 Radiotherapy in the neo-adjuvant setting is allowed and must be completed at least 4 weeks prior to initiation of study treatment. •Prior exposure to systemic chemotherapy Chemotherapy for early-stage of malignancy with curative intent, provided that the last dose received was more than 5 years prior to enrollment, may be allowed upon approval by the Medical Monitor. •Prior exposure to ALK inhibitors •Stage IIIA N2 patients that, in the investigator's opinion, should receive PORT are excluded from the study PORT is not allowed in the study. •Known sensitivity to any component of study drug (alectinib or planned chemotherapy) 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 DFS or OS for the current NSCLC •Any GI disorder that may affect absorption of oral medications, such as malabsorption syndrome or status postmajor bowel resection •Liver disease characterized by any of the following: ALT and AST 3 ULN 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. Active viral hepatitis B is defined as having positive hepatitis B surface antigen (HBsAg). Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (hepatitis B core antibody [HBcAb] – HbcAb positive, but negative HBsAg) are eligible only if the HBV DNA test is negative. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. •Any exclusion criteria based on local labels or guidelines for chemotherapy •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 tria
Outcome results
None listed