Clinical Trials /

ALTA-1L Study: A Phase 3 Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-small Cell Lung Cancer (NSCLC) Participants

NCT02737501

Description:

A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) versus Crizotinib in ALK-positive Advanced Lung Cancer Participants.

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

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

ALTA-1L Study: A Phase 3 Study of Brigatinib Versus <span class="go-doc-concept go-doc-intervention">Crizotinib</span> in <span class="go-doc-concept go-doc-biomarker">ALK</span>-positive Advanced Non-Small Cell Lung Cancer Patients

Title

  • Brief Title: ALTA-1L Study: A Phase 3 Study of Brigatinib Versus Crizotinib in ALK-positive Advanced Non-Small Cell Lung Cancer Patients
  • Official Title: A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) Versus Crizotinib in Patients With ALK-positive Advanced Lung Cancer
  • Clinical Trial IDs

    NCT ID: NCT02737501

    ORG ID: AP26113-13-301

    Trial Conditions

    Non-small Cell Lung Cancer

    Lung Cancer

    Advanced Malignancies

    Carcinoma

    Trial Interventions

    Drug Synonyms Arms
    Brigatinib Brigatinib
    Xalkori (crizotinib) Crizotinib Crizotinib

    Trial Purpose

    A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) versus Crizotinib in
    ALK-positive Advanced Lung Cancer Patients

    Detailed Description

    The purpose of this phase III, randomized, open-label, comparative, multicenter,
    international study is to compare the efficacy and safety of brigatinib to that of
    crizotinib in anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic
    non-small cell lung cancer (NSCLC) patients who have not previously been treated with an ALK
    inhibitor. Participants will be randomized in a 1:1 ratio to receive either brigatinib, 90
    milligrams (mg) orally once daily (QD) for 7 days, then a 180 mg orally QD, or crizotinib,
    250 mg orally twice daily (BID). Participants will receive treatment until disease
    progression, intolerable toxicity, consent withdrawal, or death. The total estimated
    duration of the study is at least 5 years, including 2 years to accrue patients, with at
    least 3 years for treatment and follow-up.

    Trial Arms

    Name Type Description Interventions
    Brigatinib Experimental Brigatinib will be administered orally to eligible patients with locally advanced or metastatic ALK+ NSCLC nave to ALK inhibitors at a dose of 90 mg QD for 7 days, then 180 mg QD, continuously, with or without food until disease progression, unacceptable toxicity, withdrawal of consent or death. Brigatinib
    Crizotinib Active Comparator Crizotinib will be administered to eligible patients with locally advanced or metastatic ALK+ NSCLC nave to ALK inhibitors as 250 mg orally BID, with or without food until disease progression, unacceptable toxicity, withdrawal of consent or death. Xalkori (crizotinib)

    Eligibility Criteria

    Inclusion Criteria:

    1. Have histologically or cytologically confirmed stage IIIB (and not a candidate for
    definitive multimodality therapy) or stage IV NSCLC.

    2. Must have documented ALK rearrangement.

    3. Have sufficient tumor tissue available for central analysis.

    4. Have at least 1 measurable (i.e., target) lesion per RECIST v1.1.

    5. Recovered from toxicities related to prior anticancer therapy to NCI CTCAE v 4.0
    grade 1.

    6. Are a male or female patient 18 years old.

    7. Have adequate organ function, as defined by the study protocol.

    8. Have Eastern Cooperative Oncology Group (ECOG) performance status 2.

    9. Have normal QT interval on screening ECG evaluation, defined as QT interval corrected
    (Fridericia) (QTcF) of 450 milliseconds (msec) in males or 470 msec in females.

    10. For female patients of childbearing potential, have a negative pregnancy test
    documented prior to randomization.

    11. For female and male patients who are fertile, agree to use a highly effective form of
    contraception, as defined by the study protocol.

    12. Provide signed and dated informed consent indicating that the patient has been
    informed of all pertinent aspects of the study, including the potential risks, and is
    willingly participating.

    13. Have the willingness and ability to comply with scheduled visit and study procedures.

    Exclusion Criteria:

    1. Previously received an investigational antineoplastic agent for NSCLC.

    2. Previously received any prior TKI, including ALK-targeted TKIs.

    3. Previously received more than 1 regimen of systemic anticancer therapy for locally
    advanced or metastatic disease.

    4. Received chemotherapy or radiation within 14 days of first dose of study drug, except
    stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT).

    5. Received anti-neoplastic monoclonal antibodies within 30 days of the first dose of
    study drug.

    6. Had major surgery within 30 days of the first dose of study drug, minor surgical
    procedures such as catheter placement or minimally invasive biopsies are allowed.

    7. Have been diagnosed with another primary malignancy other than NSCLC, except for
    adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively
    treated non-metastatic prostate cancer; or patients with another primary malignancy
    who are definitively relapse-free with at least 3 years elapsed since the diagnosis
    of the other primary malignancy.

    8. Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening or
    asymptomatic disease requiring an increasing dose of corticosteroids to control
    symptoms within 7 days prior to randomization.

    9. Have current spinal cord compression (symptomatic or asymptomatic and detected by
    radiographic imaging). Patients with leptomeningeal disease and without cord
    compression are allowed.

    10. Be pregnant, planning a pregnancy, or breastfeeding

    11. Have significant, uncontrolled, or active cardiovascular disease, as defined by the
    study protocol.

    12. Have uncontrolled hypertension.

    13. Have a history or the presence at baseline of pulmonary interstitial disease,
    drug-related pneumonitis, or radiation pneumonitis.

    14. Have an ongoing or active infection.

    15. Have a known history of human immunodeficiency virus (HIV) infection.

    16. Have a known or suspected hypersensitivity to brigatinib or its excipients and/or
    crizotinib or its excipients.

    17. Have malabsorption syndrome or other gastrointestinal (GI) illness or condition.

    18. Have any condition or illness that, in the opinion of the investigator, would
    compromise patient safety or interfere with the evaluation of the study drug.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression-free survival (PFS) as assessed by a blinded Independent Review Committee (bIRC)

    Secondary Outcome Measures

    Objective response rate (ORR)

    Intracranial ORR

    Intracranial PFS

    Overall Survival (OS)

    Health-related quality of life (HRQoL)

    Percentage of patients with adverse events

    Steady state pharmacokinetic (PK) parameter: Maximum Plasma Concentration [Cmax]

    Steady state pharmacokinetic (PK) parameter: Minimum plasma concentration [Cmin]

    Steady state pharmacokinetic (PK) parameter: Area Under the Curve [AUC]

    Steady state pharmacokinetic (PK) parameter: Time to maximum plasma concentration (Tmax)

    Steady state pharmacokinetic (PK) parameter: Apparent oral clearance [CL/F]

    Trial Keywords

    Non-small cell lung cancer

    Non-small cell lung carcinoma

    Epithelial lung cancer

    Squamous cell carcinoma

    Large cell carcinoma

    Adenocarcinoma

    Carcinoma

    Anaplastic Lymphoma Kinase (ALK)

    Advanced Cancers

    Brigatinib

    AP26113