Clinical Trials /

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

NCT02737501

Description:

The purpose of the study is to compare the efficacy of brigatinib to that of crizotinib in ALK+ locally advanced or metastatic non-small cell lung cancer (NSCLC) participants naive to ALK inhibitors, as evidenced by progression-free survival (PFS).

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

Completed

Phase:

Phase 3

Trial Eligibility

Document

Title

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

  • ORG STUDY ID: AP26113-13-301
  • SECONDARY ID: U1111-1210-4363
  • SECONDARY ID: 2015-003447-19
  • NCT ID: NCT02737501

Conditions

  • Non-small Cell Lung Cancer
  • Lung Cancer
  • Advanced Malignancies
  • Carcinoma

Interventions

DrugSynonymsArms
BrigatinibBrigatinib
CrizotinibXalkoriCrizotinib

Purpose

The purpose of the study is to compare the efficacy of brigatinib to that of crizotinib in ALK+ locally advanced or metastatic non-small cell lung cancer (NSCLC) participants naive to ALK inhibitors, as evidenced by progression-free survival (PFS).

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 ALK+ locally advanced or metastatic NSCLC participants who have not previously been
      treated with an ALK inhibitor. Participants will be stratified by the presence of CNS
      metastases at baseline and prior chemotherapy used for locally advanced or metastatic
      disease. Participants will be randomized in a 1:1 ratio to receive either brigatinib, 90 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. Crossover from crizotinib to brigatinib is also
      permitted.

      The total estimated duration of the study is at least 4.5 years, including 1.5 years to
      accrue participants, with at least 3 years for treatment and follow-up.
    

Trial Arms

NameTypeDescriptionInterventions
BrigatinibExperimentalBrigatinib will be administered orally to eligible participants with locally advanced or metastatic ALK+NSCLC naive to ALK inhibitors at a dose of 90 milligram (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
CrizotinibActive ComparatorCrizotinib will be administered to eligible participants with locally advanced or metastatic ALK+ NSCLC naive to ALK inhibitors as 250 mg orally BID, with or without food until disease progression, unacceptable toxicity, withdrawal of consent or death.
  • Crizotinib

Eligibility Criteria

        Inclusion Criteria:

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

          2. Must have documented ALK rearrangement.

          3. Have sufficient tumor tissue available for central analysis.

          4. Have at least 1 measurable (that is, target) lesion per RECIST v1.1.

          5. Recovered from toxicities related to prior anticancer therapy to National Cancer
             Institute (of the United States) (NCI) Common Terminology Criteria for Adverse Events
             (version 4.0) (CTCAE v 4.0) grade be less than or equal to (<=) 1.

          6. Are a male or female participants greater than or equal to (>=)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 millisecond (msec) in males or <=470 msec in females.

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

         11. For female and male participants 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 participants 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 tyrosine kinase inhibitor (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 participants 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). Participants 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 participant's safety or interfere with the evaluation of the study drug.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free Survival (PFS)
Time Frame:Baseline up to approximately 36 months
Safety Issue:
Description:PFS as assessed by blinded Independent Review Committee (BIRC) is defined as the time interval from the date of randomization until the first date at which disease progression (PD) is objectively documented, or death due to any cause, whichever occurs first. PD is sum of longest diameter (SLD) increased by at least 20 percent (%) from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 millimeter (mm), and unequivocal progression of existing non-target lesions.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Baseline up to approximately 36 months
Safety Issue:
Description:ORR as assessed by BIRC, is defined as percentage of participants who are confirmed to have achieved complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) version (v). 1.1 criteria. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to less than (<) 10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in SLD of target lesions, taking as reference baseline sum diameters. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions.
Measure:Intracranial ORR
Time Frame:Baseline up to approximately 36 months
Safety Issue:
Description:Intracranial ORR as assessed by BIRC, is defined as the percentage of the participants who have achieved CR or PR in the central nervous system (CNS) in randomized participants with intracranial CNS metastasis at baseline. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions.
Measure:Intracranial PFS
Time Frame:Baseline up to approximately 36 months
Safety Issue:
Description:Intracranial PFS as assessed by BIRC, is defined as the time from randomization until first CNS PD is documented, or death due to any cause. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions.
Measure:Overall Survival (OS)
Time Frame:Baseline up to approximately 36 months
Safety Issue:
Description:Overall survival is defined as the time from randomization until death due to any cause.
Measure:Duration of Response
Time Frame:Baseline up to approximately 36 months
Safety Issue:
Description:Duration of response as assessed by BIRC, is defined as the time interval from the date that the criteria are first met for CR/PR (whichever is first recorded) until the first date that progressive disease (PD) is objectively documented. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30 % decrease in the SLD of target lesions, taking as reference the baseline sum diameters. PD is SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest), the SLD must also demonstrate an absolute increase of at least 5 mm, and for non-target lesions, unequivocal progression of existing non-target lesions.
Measure:Time to Response (TTR)
Time Frame:Baseline up to approximately 36 months
Safety Issue:
Description:Time to response as assessed by BIRC, assessment and is defined as the time interval from the date randomization until the initial observation of CR or PR. CR is defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR is at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters.
Measure:Disease Control Rate (DCR)
Time Frame:Baseline up to approximately 36 months
Safety Issue:
Description:Disease control as assessed by BIRC, defined as percentage of randomized participants who have achieved CR, PR, or stable disease (SD) (in the case of SD, criteria for SD must have been met at least once after randomization at a minimum interval of 6 weeks) after randomization. CR defined as disappearance of all extranodal target and non-target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis for target lesions and all lymph nodes must be non-pathological in size (<10 mm short axis), normalization of tumor marker level for non-target lesions. PR: at least a 30% decrease in SLD of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: SLD increased by at least 20% from the smallest value on study, SLD must also demonstrate an absolute increase of at least 5 mm, and unequivocal progression of existing non-target lesions.
Measure:Health-related Quality of Life (HRQoL)
Time Frame:Baseline until 30 days after the last dose of study treatment (approximately 3 years)
Safety Issue:
Description:HRQoL is defined as the perceived quality of the participant's life, which includes self-reported multidimensional measures of physical and mental health. Patient-reported symptoms (PROs) and HRQoL will be collected by administering the european organisation for research and treatment of cancer (EORTC) quality of life (QLQ)-C30 questionnaire. EORTC-QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale. The 30 items have 4 response levels (not at all, a little, quite a bit, and very much), with 2 questions relying on a 7-point numeric rating scale. Raw scores are converted into scale scores ranging from 0 to 100. For functional scales and QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL.
Measure:Percentage of Participants with Adverse Events
Time Frame:Baseline until 30 days after the last dose of study treatment (approximately 3 years)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Ariad Pharmaceuticals

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

Last Updated

December 23, 2020