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

• ClinicalTrials.gov Identifier: NCT03456076
• Recruitment Status: Active, not recruiting
• First Posted: March 7, 2018
• Last Update Posted: January 23, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: March 6, 2018
• First Posted Date: March 7, 2018
• Last Update Posted Date: January 23, 2023
• Actual Study Start Date: August 16, 2018
• Estimated Primary Completion Date: June 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 27, 2018)

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 ]

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

Original Primary Outcome Measures (submitted: March 6, 2018)

Disease-free Survival (DFS), as Assessed by the Investigator [ Time Frame: Up to approximately 5 years ]

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

Current Secondary Outcome Measures (submitted: June 27, 2018)

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

Original Secondary Outcome Measures (submitted: March 6, 2018)

• Overall Survival (OS) [ Time Frame: Approximately 5 Years after First Patient In ]
  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.
• Plasma Concentration of Alectinib [ Time Frame: Predose (2 hours) at Baseline, Week 3, 6, 9, 12, 24, 36, 48, 60, 72, 84, and 96 ]
• 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 ]
• Percentage of Participants with Adverse Advent [ Time Frame: Approximately 5 years after FPI ]
  Incidence of Adverse Events, with Severity Determined Through Use of National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 Safety Laboratory Values, Vital Signs, ECG

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Non-Small-Cell Lung

Intervention

• Drug: Alectnib
  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.
  Other Name: RO5424802
• Drug: Cisplatin
  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."
• Drug: Vinorelbine
  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.
  Other Name: Navelbine
• Drug: Gemcitabine
  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.
  Other Name: Gitrabin
• Drug: Pemetrexed
  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."
  Other Name: Alimta®
• Drug: Carboplatin
  For participants who experience unacceptable toxicity with cisplatin, carboplatin can be used.

Study Arms

• Experimental: Alectinib
  Intervention: Drug: Alectnib
• Active Comparator: Platinum-Based Chemotherapy
  Interventions:

  • Drug: Cisplatin
  • Drug: Vinorelbine
  • Drug: Gemcitabine
  • Drug: Pemetrexed
  • Drug: Carboplatin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 8, 2022): 257
• Original Estimated Enrollment (submitted: March 6, 2018): 255
• Estimated Study Completion Date: November 19, 2026
• Estimated Primary Completion Date: June 30, 2023 (Final data collection date for primary outcome measure)

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 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belarus, Bosnia and Herzegovina, China, Denmark, Egypt, France, Germany, Greece, Hungary, Israel, Italy, Japan, Kazakhstan, Korea, Republic of, North Macedonia, Poland, Romania, Russian Federation, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Latvia, Lebanon, Macedonia, The Former Yugoslav Republic of, Portugal, Saudi Arabia, Singapore, South Africa

Administrative Information

• NCT Number: NCT03456076
• Other Study ID Numbers: BO40336; 2017-004331-37 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: January 2023