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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 : April 11, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Ariad Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE March 30, 2016
First Posted Date  ICMJE April 14, 2016
Last Update Posted Date April 11, 2019
Actual Study Start Date  ICMJE May 26, 2016
Estimated Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 11, 2016)
Progression-free survival (PFS) as assessed by a blinded Independent Review Committee (bIRC) [ Time Frame: At least 36 months ]
Change History Complete list of historical versions of study NCT02737501 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline until 30 days after the last dose of study treatment (approximately 3 years) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 11, 2016)
  • Objective response rate (ORR) [ Time Frame: At least 36 months ]
    Defined as the proportion of the patients who are confirmed to have achieved CR or PR using RECIST v. 1.1 criteria.
  • Intracranial ORR [ Time Frame: At least 36 months ]
    Defined as the proportion of the patients who have achieved CR or PR in the CNS.
  • Intracranial PFS [ Time Frame: At least 36 months ]
    Defined as the time from randomization until first CNS disease progression is documented, or death due to any cause.
  • Overall Survival (OS) [ Time Frame: At least 36 months. ]
    Defined as the time from randomization until death due to any cause.
  • Health-related quality of life (HRQoL) [ Time Frame: Until 30 days after the last dose of study treatment. ]
    Defined as the perceived quality of the patient's life, which includes self-reported multidimensional measures of physical and mental health.
  • Percentage of patients with adverse events [ Time Frame: Until at least 30 days after the last dose of study treatment. ]
    To evaluate the safety and tolerability of brigatinib in the Intention to Treat (ITT) population. Measured by routine physical and laboratory evaluations, ECG, and adverse event (AE) monitoring.
  • Steady state pharmacokinetic (PK) parameter: Maximum Plasma Concentration [Cmax] [ Time Frame: Up to 28 months. ]
    PK samples will be taken to assess limited elements of PK in the Treated population.
  • Steady state pharmacokinetic (PK) parameter: Minimum plasma concentration [Cmin] [ Time Frame: Up to 28 months. ]
    PK samples will be taken to assess limited elements of PK in the Treated population.
  • Steady state pharmacokinetic (PK) parameter: Area Under the Curve [AUC] [ Time Frame: Up to 28 months. ]
    PK samples will be taken to assess limited elements of PK in the Treated population.
  • Steady state pharmacokinetic (PK) parameter: Time to maximum plasma concentration (Tmax) [ Time Frame: Up to 28 months. ]
    PK samples will be taken to assess limited elements of PK in the Treated population.
  • Steady state pharmacokinetic (PK) parameter: Apparent oral clearance [CL/F] [ Time Frame: Up to 28 months. ]
    PK samples will be taken to assess limited elements of PK in the Treated population.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) Versus Crizotinib in Patients With ALK-positive Advanced Lung Cancer
Brief Summary A Phase 3 Multicenter Open-label Study of Brigatinib (AP26113) versus Crizotinib in ALK-positive Advanced Lung Cancer Participants.
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  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
  • Non-small Cell Lung Cancer
  • Lung Cancer
  • Advanced Malignancies
  • Carcinoma
Intervention  ICMJE
  • 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.
  • 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: Brigatinib
  • 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.
    Intervention: Drug: Crizotinib
Publications *

*   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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 9, 2018)
275
Original Estimated Enrollment  ICMJE
 (submitted: April 11, 2016)
270
Estimated Study Completion Date  ICMJE July 31, 2020
Estimated Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Canada,   Denmark,   France,   Germany,   Hong Kong,   Italy,   Korea, Republic of,   Luxembourg,   Netherlands,   Norway,   Singapore,   Spain,   Sweden,   Switzerland,   Taiwan,   United Kingdom,   United States
Removed Location Countries Finland
 
Administrative Information
NCT Number  ICMJE NCT02737501
Other Study ID Numbers  ICMJE AP26113-13-301
U1111-1210-4363 ( Other Identifier: World Health Organization )
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
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.
Responsible Party Takeda ( Ariad Pharmaceuticals )
Study Sponsor  ICMJE Ariad Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Takeda
Verification Date April 2019

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