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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 : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Ariad Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
ALK+ Advanced NSCLC Drug: Brigatinib Drug: Alectinib Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 246 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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®)
Actual Study Start Date : April 19, 2019
Estimated Primary Completion Date : December 4, 2021
Estimated Study Completion Date : December 5, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Brigatinib
Brigatinib Tablets.
Other Name: Alunbrig

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.
Drug: Alectinib
Alectinib Capsules.
Other Name: Alecensa




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.



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 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.

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): NCT03596866


Contacts
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Contact: Takeda Study Registration Call Center +1-866-835-2233 globaloncologymedinfo@takeda.com

  Show 108 Study Locations
Sponsors and Collaborators
Ariad Pharmaceuticals
Investigators
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Study Director: Medical Director Clinical Science Ariad Pharmaceuticals

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Responsible Party: Ariad Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03596866     History of Changes
Other Study ID Numbers: Brigatinib-3001
2018-001957-29 ( EudraCT Number )
First Posted: July 24, 2018    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: August 2019
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda ( Ariad Pharmaceuticals ):
Drug Therapy
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Crizotinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action