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An Efficacy Study Comparing Brigatinib Versus Alectinib in Advanced Anaplastic Lymphoma Kinase-Positive (ALK+) Non-Small-Cell Lung Cancer (NSCLC) Participants Who Have Progressed on Crizotinib (ALTA-3)

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ClinicalTrials.gov Identifier: NCT03596866
Recruitment Status : Recruiting
First Posted : July 24, 2018
Last Update Posted : September 30, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Ariad Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE July 13, 2018
First Posted Date  ICMJE July 24, 2018
Last Update Posted Date September 30, 2019
Actual Study Start Date  ICMJE April 19, 2019
Estimated Primary Completion Date December 4, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
PFS as Assessed by Blinded Independent Review Committee (BIRC) per RECIST v1.1 [ Time Frame: Up to 5 years ]
PFS is defined as the time interval from the date of randomization until the first date at which disease progression is objectively documented via RECIST v1.1, or death due to any cause, whichever occurs first, in the full analysis set. PFS will be censored for participants without documented disease progression or death at the last valid tumor response assessment.
Original Primary Outcome Measures  ICMJE
 (submitted: July 13, 2018)
Progression-Free Survival (PFS) as Assessed by Blinded Independent Review Committee (BIRC) per RECIST v1.1 [ Time Frame: Up to 5 years ]
PFS is defined as the time interval from the date of randomization until the first date at which disease progression is objectively documented via RECIST v1.1, or death due to any cause, whichever occurs first, in the full analysis set. Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
Change History Complete list of historical versions of study NCT03596866 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2019)
  • Time to Intracranial Progression (iPD) as Assessed by BIRC per Modified RECIST v1.1 [ Time Frame: Up to 5 years ]
    Time to iPD, as assessed by the BIRC, is defined as the time interval from the date of randomization until the first date at which intracranial disease progression is objectively documented via a modification of RECIST v1.1. Time to iPD will be censored for participants without documented intracranial disease progression at the last valid tumor response assessment.
  • Overall Survival (OS) [ Time Frame: Up to 5 years ]
    OS is defined as the time interval from the date of randomization until death due to any cause in the full analysis set. It will be censored on the date of last contact for those participants who are alive.
  • Objective Response Rate (ORR) as Assessed by Investigator and BIRC per RECIST v1.1 [ Time Frame: Up to 5 years ]
    ORR is defined as the percentage of the participants who are confirmed to have achieved complete response (CR) or partial response (PR), using RECIST v1.1 after the initiation of study treatment.
  • Time to Response as Assessed by Investigator and BIRC [ Time Frame: Up to 5 years ]
    Time to response is defined as the time interval from randomization until the initial observation of CR or PR, as assessed by the investigator and BIRC, using RECIST v1.1. Time to response will be summarized using descriptive statistics in participants with confirmed objective response.
  • Duration of Response (DOR) as Assessed by BIRC [ Time Frame: Up to 5 years ]
    DOR is defined as the time interval from the time that the measurement criteria are first met for CR or PR (whichever is first recorded) until the first date that the progressive disease (PD) is objectively documented or death, as assessed by the investigator and BIRC, using RECIST v1.1.
  • Intracranial Objective Response Rate (iORR) as Assessed by BIRC per Modified RECIST v1.1 [ Time Frame: Up to 5 years ]
    iORR, as assessed by the BIRC, is defined as the percentage of the participants who have achieved CR or PR in the central nervous system (CNS) per a modification RECIST v1.1 after the initiation of study treatment in participant with CNS metastases at enrollment.
  • Intracranial Duration of Response (iDOR) as Assessed by the BIRC per Modified RECIST v1.1 [ Time Frame: Up to 5 years ]
    iDOR, as assessed by the BIRC per modified RECIST v1.1, is defined as the time interval from the time that the measurement criteria are first met for CR or PR in the CNS (whichever is first recorded) until the first date that the PD in the CNS is objectively documented or death.
  • Health-Related Quality of Life (HRQOL) from European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 v3.0) Score [ Time Frame: First dose of study drug up to 30 days after last dose (approximately 9 years) ]
    EORTC QLQ-C30 incorporates 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) and 2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status scale, higher scores represent better quality of life (QOL); for the symptom scales, lower scores represent better QOL.
  • HRQOL from EORTC QLQ- Lung Cancer (LC) 13 [ Time Frame: First dose of study drug up to 30 days after last dose (approximately 9 years) ]
    HRQOL scores will be assessed with European Organization for Research and Treatment (EORTC), its lung cancer module QLQ-LC13. QLQ-LC13 contains 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. Scale score range: 0 to 100. Higher symptom score = greater degree of symptom severity.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2018)
  • Intracranial Progression-Free Survival (iPFS) as Assessed by BIRC per modified RECIST v1.1 [ Time Frame: Up to 5 years ]
    iPFS is defined as the time interval from the date of randomization until the first date at which intracranial disease progression is objectively documented via a modification of RECIST v1.1, or death due to any cause, whichever occurs first. Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
  • Overall Survival (OS) [ Time Frame: Up to 9 years ]
    OS is defined as the time interval from the date of randomization until death due to any cause.
  • Objective Response Rate (ORR) as Assessed by Investigator and BIRC per RECIST v1.1 [ Time Frame: Up to 5 years ]
    ORR is defined as the proportion of the participants who are confirmed to have achieved complete response (CR) or partial response (PR), using RECIST v1.1 after the initiation of study treatment. CR is defined as disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters.
  • Time to Response as Assessed by Investigator and BIRC [ Time Frame: Up to 5 years ]
    Time to response is defined as the time interval from randomization until the initial observation of CR or PR. CR is defined as disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters.
  • Duration of Response (DOR) as Assessed by Investigator and BIRC [ Time Frame: Up to 5 years ]
    DOR is defined as the time interval from the time that the measurement criteria are first met for CR or PR (whichever is first recorded) until the first date that the PD is objectively documented or death. CR is defined as disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. Progressive disease (PD) is defined as SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest). SLD must also demonstrate an absolute increase of at least 5 mm (2 lesions increasing from, for example, 2 mm to 3 mm, does not qualify) is objectively documented or death.
  • Intracranial Objective Response Rate (iORR) as Assessed by BIRC per Modified RECIST v1.1 [ Time Frame: Up to 5 years ]
    iORR is defined as the proportion of the participants who have achieved CR or PR in the CNS per a modification RECIST v1.1 after the initiation of study treatment in participant with CNS metastases at enrollment. CR is defined as disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters in the central nervous system (CNS).
  • Intracranial Duration of Response (iDOR) as Assessed by the BIRC per Modified RECIST v1.1 [ Time Frame: Up to 5 years ]
    iDOR is defined as the time interval from the time that the measurement criteria are first met for CR or PR in the CNS (whichever is first recorded) until the first date that the PD in the CNS is objectively documented or death. CR is defined as disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as at least a 30% decrease in the SLD of target lesions, taking as reference the baseline sum diameters. PD is defined as SLD increased by at least 20% from the smallest value on study (including baseline, if that is the smallest). SLD must also demonstrate an absolute increase of at least 5 mm (2 lesions increasing from, for example, 2 mm to 3 mm, does not qualify) is objectively documented or death.
  • Health-Related Quality of Life (HRQOL) from European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 v3.0) Score [ Time Frame: First dose of study drug up to 30 days after last dose (approximately 9 years) ]
    EORTC QLQ-C30 incorporates 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all [best] to 4=Very Much [worst]) and 2 questions (7-point scale where 1=Very poor [worst] to 7= Excellent [best]). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status scale, higher scores represent better quality of life (QOL); for the symptom scales, lower scores represent better QOL.
  • HRQOL from EORTC QLQ- Lung Cancer (LC) 13 [ Time Frame: First dose of study drug up to 30 days after last dose (approximately 9 years) ]
    HRQOL scores will be assessed with EORTC, its lung cancer module QLQ-LC13. QLQ-LC13 contains 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. Scale score range: 0 to 100. Higher symptom score = greater degree of symptom severity.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Efficacy Study Comparing Brigatinib Versus Alectinib in Advanced Anaplastic Lymphoma Kinase-Positive (ALK+) Non-Small-Cell Lung Cancer (NSCLC) Participants Who Have Progressed on Crizotinib
Official Title  ICMJE A Phase 3 Randomized Open-label Study of Brigatinib (ALUNBRIG®) Versus Alectinib (ALECENSA®) in Advanced Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer Patients Who Have Progressed on Crizotinib (XALKORI®)
Brief Summary The purpose of this study is to compare the efficacy of brigatinib versus alectinib in participants with ALK+ locally advanced or metastatic NSCLC who have progressed on crizotinib as evidenced by progression-free survival (PFS) as assessed by response evaluation criteria in solid tumors (RECIST) v1.1.
Detailed Description

The drug being tested in this study is called brigatinib. Brigatinib has been demonstrated to benefit people with ALK+ NSCLC.

The comparator drug is called alectinib. Alectinib has been demonstrated to benefit people with ALK+ NSCLC. Both drugs belong to a class of drugs called anaplastic lymphoma kinase (ALK) inhibitors. Both drugs are taken by mouth. Both drugs are approved by the United States Food and Drug Administration (US FDA).

The study will enroll approximately 246 participants. Participants will be randomly assigned (by chance, like flipping a coin) in 1:1 ratio to one of the two treatment groups:

  • Brigatinib
  • Alectinib

All participants will be asked to take brigatinib or alectinib at the same time each day throughout the study.

This multi-center trial will be conducted the United States, Argentina, Austria, Canada, Chile, China, Croatia, France, Germany, Greece, Hong Kong, Italy, Mexico, Romania, Russia, South Korea, Spain, Sweden, Taiwan, Thailand. The overall time to participate in this study is 5 years. Participants will make multiple visits to the clinic, and 30 days after last dose of study drug for a follow-up assessment.

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 ALK+ Advanced NSCLC
Intervention  ICMJE
  • Drug: Brigatinib
    Brigatinib Tablets.
    Other Name: Alunbrig
  • Drug: Alectinib
    Alectinib Capsules.
    Other Name: Alecensa
Study Arms  ICMJE
  • Experimental: Brigatinib
    Brigatinib 90 milligram (mg), tablets, orally, once daily 7 days, followed by Brigatinib 180 mg, tablets, orally, once daily for until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity.
    Intervention: Drug: Brigatinib
  • Active Comparator: Alectinib
    Alectinib 600 mg, capsules, orally twice daily until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity.
    Intervention: Drug: Alectinib
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: July 13, 2018)
246
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 5, 2022
Estimated Primary Completion Date December 4, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  2. Have histologically or cytologically confirmed stage IIIB (locally advanced or recurrent) or stage IV NSCLC.
  3. Must meet one of the following criteria:

    • Have documentation of ALK rearrangement by a positive result from the Vysis ALK Break-Apart fluorescence in situ hybridization (FISH) Probe Kit or the Ventana ALK (D5F3) CDx Assay or Foundation Medicine's FoundationOne CDx.
    • Have documented ALK rearrangement by a different test and be able to provide tumor sample to the central laboratory. (Note: central laboratory ALK rearrangement testing results are not required to be obtained before randomization).
  4. Had PD while on crizotinib, as assessed by the investigator or treating physician. (Note: crizotinib does not need to be the last therapy a participant received. The participant may have received chemotherapy as his/her last therapy).
  5. Treatment with crizotinib for at least 4 weeks before progression.
  6. Have had no other ALK inhibitor other than crizotinib.
  7. Have had no more than 2 prior regimens of systemic anticancer therapy (other than crizotinib) in the locally advanced or metastatic setting. Note: a systemic anticancer therapy regimen will be counted if it is administered for at least 1 complete cycle. A new anticancer agent used as maintenance therapy will be counted as a new regimen. Neoadjuvant or adjuvant systemic anticancer therapy will be counted as a prior regimen if disease progression/recurrence occurred within 12 months upon completion of this neoadjuvant or adjuvant therapy. (Systemic therapy followed by maintenance therapy will be considered as one regimen if the maintenance therapy consists of a drug or drugs that were used in the regimen that immediately preceded maintenance).
  8. Have at least 1 measurable (that is, target) lesion per RECIST v1.1.
  9. Have recovered from toxicities related to prior anticancer therapy to national cancer institute common terminology criteria for adverse events (NCI CTCAE) v4.03 grade less than or equal to (<=)1. (Note: treatment-related alopecia or peripheral neuropathy that are grade greater than (>) 1 are allowed, if deemed irreversible).
  10. Have adequate organ function, as determined by:

    • Total bilirubin <=1.5 times the upper limit of normal (ULN).
    • Estimated glomerular filtration rate greater than equal to (>=) 30 milliliter per minute (mL/min)/1.73 square meter [m^2], using the modification of diet in renal disease equation.
    • Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <=2.5*ULN; <=5*ULN is acceptable if liver metastases are present.
    • Serum lipase <=1.5*ULN.
    • Platelet count >=75*10^9 per liter [/L].
    • Hemoglobin >=9 gram per deciliter (g/dL).
    • Absolute neutrophil count >=1.5*10^9 / L.
  11. Suitable venous access for study-required blood sampling (that is, including pharmacokinetic [PK] and laboratory safety tests).

Exclusion Criteria:

  1. Had participated in the control (crizotinib) arm of Study AP26113-13-301 (ALTA 1L).
  2. Had received crizotinib within 7 days of randomization.
  3. Have a history or presence at baseline of pulmonary interstitial disease, drug related pneumonitis, or radiation pneumonitis.
  4. Have uncontrolled hypertension. Participants with hypertension should be under treatment for control of blood pressure upon study entry.
  5. Had received systemic treatment with strong cytochrome P-450 (CYP) 3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, or moderate CYP3A inducers within 14 days before randomization.
  6. Treatment with any investigational systemic anticancer agents within 14 days or 5 half-lives, whichever is longer, before randomization.
  7. Had received chemotherapy or radiation therapy within 14 days of randomization except for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy.
  8. Had received antineoplastic monoclonal antibodies within 30 days of randomization.
  9. Had major surgery within 30 days of randomization. Minor surgical procedures, such as catheter placement or minimally invasive biopsies, are allowed.
  10. Have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening (participants with asymptomatic brain metastases or participants who have stable symptoms and did not require an increased dose of corticosteroids to control symptoms within 7 days before randomization will be enrolled). Note: If a participant has worsening neurological symptoms or signs due to CNS metastasis, the participant needs to complete local therapy and be neurologically stable (with no requirement for an increasing dose of corticosteroids or use of anticonvulsants) for 7 days before randomization.
  11. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with leptomeningeal disease and without cord compression are allowed.
  12. Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to the following:

    • Myocardial infarction within 6 months before randomization.
    • Unstable angina within 6 months before randomization.
    • New York Heart Association Class III or IV heart failure within 6 months before randomization.
    • History of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician.
    • Any history of clinically significant ventricular arrhythmia.
  13. Had cerebrovascular accident or transient ischemic attack within 6 months before first dose of study drug.
  14. Have malabsorption syndrome or other gastrointestinal illness or condition that could affect oral absorption of the study drug.
  15. Have an ongoing or active infection, including but not limited to, the requirement for intravenous antibiotics.
  16. Have a known history of human immunodeficiency virus (HIV) infection. Testing is not required in the absence of history.
  17. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
  18. Have a known or suspected hypersensitivity to brigatinib or alectinib or their excipients.
  19. Life-threatening illness unrelated to cancer.
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: Takeda Study Registration Call Center +1-866-835-2233 globaloncologymedinfo@takeda.com
Listed Location Countries  ICMJE Argentina,   Austria,   Canada,   Chile,   China,   Croatia,   France,   Germany,   Greece,   Hong Kong,   Italy,   Korea, Republic of,   Mexico,   Romania,   Russian Federation,   Spain,   Sweden,   Taiwan,   Thailand,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03596866
Other Study ID Numbers  ICMJE Brigatinib-3001
2018-001957-29 ( 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
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com 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
Study Director: Medical Director Clinical Science Ariad Pharmaceuticals
PRS Account Takeda
Verification Date September 2019

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