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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03456076
Recruitment Status : Recruiting
First Posted : March 7, 2018
Last Update Posted : November 10, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE March 6, 2018
First Posted Date  ICMJE March 7, 2018
Last Update Posted Date November 10, 2020
Actual Study Start Date  ICMJE August 16, 2018
Estimated Primary Completion Date June 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE A Study Comparing Adjuvant Alectinib Versus Adjuvant Platinum-Based Chemotherapy in Patients With ALK Positive Non-Small Cell Lung Cancer
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Carcinoma, Non-Small-Cell Lung
Intervention  ICMJE
  • 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  ICMJE
  • Experimental: Alectinib
    Intervention: Drug: Alectnib
  • Active Comparator: Platinum-Based Chemotherapy
    Interventions:
    • Drug: Cisplatin
    • Drug: Vinorelbine
    • Drug: Gemcitabine
    • Drug: Pemetrexed
    • Drug: Carboplatin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 6, 2018)
255
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 19, 2026
Estimated Primary Completion Date June 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Reference Study ID Number: BO40336 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com
Listed Location Countries  ICMJE Australia,   Austria,   Belarus,   Bosnia and Herzegovina,   China,   Denmark,   Egypt,   France,   Germany,   Greece,   Hungary,   Israel,   Italy,   Japan,   Kazakhstan,   Korea, Republic of,   Latvia,   Lebanon,   North Macedonia,   Poland,   Portugal,   Romania,   Russian Federation,   Saudi Arabia,   Singapore,   South Africa,   Spain,   Taiwan,   Thailand,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Macedonia, The Former Yugoslav Republic of
 
Administrative Information
NCT Number  ICMJE NCT03456076
Other Study ID Numbers  ICMJE 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  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP