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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 (ALTA-1L)

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ClinicalTrials.gov Identifier: NCT02737501
Recruitment Status : Active, not recruiting
First Posted : April 14, 2016
Last Update Posted : August 23, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda ( Ariad Pharmaceuticals )

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

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Lung Cancer Advanced Malignancies Carcinoma Drug: Brigatinib Drug: Crizotinib Phase 3

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-positive locally advanced or metastatic NSCLC participants who have not previously been treated with an ALK inhibitor. 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.

The total estimated duration of the study is at least 5 years, including 2 years to accrue participants, with at least 3 years for treatment and follow-up.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 275 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) Versus Crizotinib in Patients With ALK-positive Advanced Lung Cancer
Actual Study Start Date : May 26, 2016
Estimated Primary Completion Date : July 31, 2020
Estimated Study Completion Date : July 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Brigatinib
Brigatinib 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.
Drug: Brigatinib
Brigatinib will be administered orally to eligible participants with locally advanced or metastatic ALK+NSCLC naive to ALK inhibitors at a dose of 90 mg QD for 7 days, then 180 mg QD, continuously, until disease progression, unacceptable toxicity, withdrawal of consent or death.

Active Comparator: Crizotinib
Crizotinib 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.
Drug: Crizotinib
Crizotinib will be administered to eligible participants with locally advanced or metastatic ALK+ NSCLC naive to ALK inhibitors as 250 mg orally BID, until disease progression, unacceptable toxicity, withdrawal of consent or death.
Other Name: Xalkori




Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: Baseline up to approximately 36 months ]
    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 :
  1. Objective Response Rate (ORR) [ Time Frame: Baseline up to approximately 36 months ]
    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.

  2. Intracranial ORR [ Time Frame: Baseline up to approximately 36 months ]
    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.

  3. Intracranial PFS [ Time Frame: Baseline up to approximately 36 months ]
    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.

  4. Overall Survival (OS) [ Time Frame: Baseline up to approximately 36 months ]
    Overall survival is defined as the time from randomization until death due to any cause.

  5. Duration of Response [ Time Frame: Baseline up to approximately 36 months ]
    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.

  6. Time to Response (TTR) [ Time Frame: Baseline up to approximately 36 months ]
    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.

  7. Disease Control Rate (DCR) [ Time Frame: Baseline up to approximately 36 months ]
    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.

  8. Health-related Quality of Life (HRQoL) [ Time Frame: Baseline until 30 days after the last dose of study treatment (approximately 3 years) ]
    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.

  9. Percentage of Participants with Adverse Events [ Time Frame: Baseline until 30 days after the last dose of study treatment (approximately 3 years) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02737501


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Sponsors and Collaborators
Ariad Pharmaceuticals

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ariad Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02737501     History of Changes
Other Study ID Numbers: AP26113-13-301
U1111-1210-4363 ( Other Identifier: World Health Organization )
First Posted: April 14, 2016    Key Record Dates
Last Update Posted: August 23, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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

Keywords provided by Takeda ( Ariad Pharmaceuticals ):
Brigatinib
AP26113
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

Additional relevant MeSH terms:
Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Crizotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action