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

NCT03456076

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: BO40336
  • SECONDARY ID: 2017-004331-37
  • NCT ID: NCT03456076

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
AlectnibRO5424802Alectinib
CisplatinPlatinum-Based Chemotherapy
VinorelbineNavelbinePlatinum-Based Chemotherapy
GemcitabineGitrabinPlatinum-Based Chemotherapy
PemetrexedAlimta®Platinum-Based Chemotherapy
CarboplatinPlatinum-Based Chemotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
AlectinibExperimental
  • Alectnib
Platinum-Based ChemotherapyActive Comparator
  • Cisplatin
  • Vinorelbine
  • Gemcitabine
  • Pemetrexed
  • Carboplatin

Eligibility 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 chemotherapy 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 acute
             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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Measure:Overall Survival (OS)
Time Frame:From the date of randomization until death due to any cause up to approximately 8 years
Safety Issue:
Description: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.
Measure:Plasma Concentration of Alectinib
Time Frame:Predose (2 hours) at Baseline, Week 3, 6, 9, 12, 24, 36, 48, 60, 72, 84, and 96
Safety Issue:
Description:
Measure:Plasma Concentration of Alectinib metabolite
Time Frame:Predose (2 hours) at Baseline, Week 3, 6, 9, 12, 24, 36, 48, 60, 72, 84, and 96
Safety Issue:
Description:
Measure:Percentage of Participants with Adverse Advent
Time Frame:From the date of randomization up to approximately 2 years
Safety Issue:
Description: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

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Trial Keywords

  • NSCLC, alectinib, ALK positive,adjuvant treatment, platinum based chemotherapy, complete resection, Stage IB-IIIA.

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