A Study of Brigatinib Compared to Alectinib in Adults With Non-Small-Cell Lung Cancer
- Registration Number
- NCT03596866
- Lead Sponsor
- Takeda
- Brief Summary
Brigatinib is a medicine that binds to the surface of tumor cells in some cancers and delivers a dose of chemotherapy directly to the tumor. In this study, participants will be people with non-small-cell lung cancer (NSCLC for short). The main aim of the study is to learn if brigatinib stops the tumors from growing, or if the tumors have shrunk or disappeared, compared to a medicine called alectinib.
At the first visit, the study doctor will check who can take part. Participants who can take part will be picked for 1 of 2 treatments by chance:
* Brigatinib tablets
* Alectinib capsules
All participants will take brigatinib or alectinib at about the same time every day. They will continue with treatment throughout the study unless their cancer gets worse, they have side effects from the treatment, they leave the study for certain reasons, or the study is stopped.
After stopping treatment, participants will visit the study clinic for a check-up 30 days later.
- Detailed Description
The drug being tested in this study is called brigatinib. Brigatinib has been demonstrated to benefit people with anaplastic lymphoma kinase-positive (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. For each participant eligible to continue in the study and to facilitate the remaining participants from Brigatinib-2002 (NCT03535740) to have continued treatment access, the study extension phase may be initiated for participants to continue receiving their randomized study treatment (i.e., brigatinib or alectinib) until they meet at least one of the treatment discontinuation criteria.
This multi-center trial will be conducted in the United States, Argentina, Austria, Canada, Chile, China, Croatia, France, Germany, Greece, Hong Kong, Italy, Mexico, Romania, Russia, South Korea, Spain, Sweden, Taiwan, and 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 248
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Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
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Have histologically or cytologically confirmed stage IIIB (locally advanced or recurrent) or stage IV NSCLC.
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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).
-
Had PD while on crizotinib, as assessed by the investigator or treating physician except for participants previously participating in the Brigatinib-2002 study (Note: crizotinib does not need to be the last therapy a participant received. The participant may have received chemotherapy as his/her last therapy).
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Treatment with crizotinib for at least 4 weeks before progression except for participants previously participating in the Brigatinib-2002 study.
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Have had no other ALK inhibitor other than crizotinib except for participants previously participating in the Brigatinib-2002 study.
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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).
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Have at least 1 measurable (that is, target) lesion per RECIST v1.1.
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Have recovered from toxicities related to prior anticancer therapy to national cancer institute common terminology criteria for adverse events (NCI CTCAE) version 4.03 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).
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Have adequate organ function, at the time of initial screening, except for participants previously participating in the Brigatinib-2002 study 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.
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Suitable venous access for study-required blood sampling (that is, including pharmacokinetic [PK] and laboratory safety tests).
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Had participated in the control (crizotinib) arm of Study AP26113-13-301 (ALTA 1L) [NCT02737501].
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Had received crizotinib within 7 days before randomization.
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Have a history or presence at baseline of pulmonary interstitial disease, drug related pneumonitis, or radiation pneumonitis.
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Have uncontrolled hypertension. Participants with hypertension should be under treatment for control of blood pressure upon study entry.
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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.
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Treatment with any investigational systemic anticancer agents within 14 days or 5 half-lives, whichever is longer, before randomization.
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Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated nonmelanoma skin cancer or cervical cancer in situ; definitively treated nonmetastatic 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.
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Had received chemotherapy or radiation therapy within 14 days before randomization except for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy.
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Had received antineoplastic monoclonal antibodies within 30 days of randomization.
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Had major surgery within 30 days of randomization. Minor surgical procedures, such as catheter placement or minimally invasive biopsies, are allowed.
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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.
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Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with leptomeningeal disease and without cord compression are allowed.
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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.
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Had cerebrovascular accident or transient ischemic attack within 6 months before first dose of study drug.
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Have malabsorption syndrome or other gastrointestinal illness or condition that could affect oral absorption of the study drug.
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Have an ongoing or active infection, including but not limited to, the requirement for intravenous antibiotics.
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Have a known history of human immunodeficiency virus (HIV) infection. Testing is not required in the absence of history.
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Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection. Testing is not required in the absence of history.
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Any serious medical condition or psychiatric illness that could, in the investigator's opinion, potentially compromise participant safety or interfere with the completion of treatment according to this protocol.
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Have a known or suspected hypersensitivity to brigatinib or alectinib or their excipients.
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Life-threatening illness unrelated to cancer.
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Female participants who are lactating and breastfeeding.
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Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Brigatinib Brigatinib Participants were administered brigatinib 90 milligrams (mg), tablets, orally, once daily (QD) for 7 days, followed by brigatinib 180 mg, tablets, orally, QD until objective disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), as assessed by the investigator, or intolerable toxicity, or up to 33.8 months. Alectinib Alectinib Participants were administered alectinib 600 mg, capsules, orally, twice daily (BID) until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity, or up to 33.8 months.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) as Assessed by Blinded Independent Review Committee (BIRC) Per RECIST v1.1 Up to 33.8 months 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 by BIRC, 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
Name Time Method Overall Survival (OS) 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.
PFS as Assessed by Investigator Per RECIST v1.1 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 by investigator, 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.
Objective Response Rate (ORR) as Assessed by Investigator and BIRC Per RECIST v1.1 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.
Duration of Response (DOR) as Assessed by Investigator and BIRC Per RECIST v1.1 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. For the responders who have not progressed or died, they will be censored at the last tumor assessment date prior to receiving subsequent anticancer therapy.
Time to Response as Assessed by Investigator and BIRC Per RECIST v1.1 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.
Intracranial Objective Response Rate (iORR) as Assessed by BIRC Per Modified RECIST v1.1 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 participants with CNS metastases at baseline.
Intracranial Duration of Response (iDOR) as Assessed by the BIRC Per Modified RECIST v1.1 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.
Time to Intracranial Disease Progression (iPD) as Assessed by BIRC Per Modified RECIST v1.1 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 iPD is objectively documented via a modification of RECIST v1.1. Time to iPD will be censored for participants without documented iPD at the last valid intracranial tumor response assessment.
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 5 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 5 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.
Trial Locations
- Locations (111)
Sanatorio Duarte Quiros
🇦🇷Cordoba, Argentina
Peking Union Medical College Hospital - East
🇨🇳Beijing, Beijing, China
Centro de Investigacion Clinica Bradford Hill
🇨🇱Recoleta, Santiago, Chile
Centre Hospitalier Intercommunal de Creteil
🇫🇷Creteil, Ile-de-france, France
Centro Para la Atencion Integral del Paciente Oncologico
🇦🇷San Miguel De Tucuman, Tucuman, Argentina
Centro Oncologico Riojano Integral
🇦🇷La Rioja, Argentina
Jilin Provincial Cancer Hospital (Changchun Cancer Hospital)
🇨🇳Changchun, Jilin, China
Klinika za Pulmologiju
🇭🇷Zagreb, Croatia
Shanghai Chest Hospital
🇨🇳Shanghai, Shanghai, China
Klinicki bolnicki centar Sestre milosrdnice
🇭🇷Zagreb, Croatia
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital Universitari Sant Joan de Reus
🇪🇸Reus, Spain
General Hospital Pula
🇭🇷Pula, Croatia
Asklepios Fachkliniken Munchen-Gauting
🇩🇪Gauting, Bayern, Germany
Karolinska Universitetssjukhuset - Solna
🇸🇪Solna, Stockholm, Sweden
Hopital Albert Michallon
🇫🇷Grenoble Cedex 9, Rhone-alpes, France
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Thoraxklinik Heidelberg
🇩🇪Heidelberg, Baden-wuerttemberg, Germany
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga
🇪🇸Malaga, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Uppsala Akademiska Sjukhus
🇸🇪Uppsala, Sweden
Changhua Christian Hospital
🇨🇳Changhua City, Taiwan
Songklanagarind Hospital
🇹🇭Songkhla, Thailand
The First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Beijing Chest Hospital
🇨🇳Beijing, Beijing, China
Peking University Cancer Hospital/Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
The 307th Hospital of Chinese Peoples Liberation Army
🇨🇳Beijing, Beijing, China
Affiliated Tumor Hospital of Harbin Medical University - The 3rd Affiliated Hospital of HMU
🇨🇳Harbin, Heilongjiang, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
The First Affiliated Hospital, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
Klinikum Klagenfurt Am Worthersee
🇦🇹Klagenfurt am Worthersee, Carinthia, Austria
Chang Gung Memorial Hospital Linkou Branch
🇨🇳Taoyuan City, Taiwan
General Oncology Hospital of Kifisia Oi Agioi Anargiroi
🇬🇷Nea Kifisia, Attica, Greece
Medica Sur
🇲🇽Ciudad de Mexico, Cdmx, Mexico
Humanity and Health Research Centre
🇭🇰Central, Hong Kong
Centro de Investigacion Medica Aguascalientes
🇲🇽Aguascalientes, Mexico
Institutul Oncologic Prof. Dr. Ion Chiricu
🇷🇴Cluj-Napoca, Cluj, Romania
Interbalkan Medical Center of Thessaloniki
🇬🇷Thessaloniki, Macedonia, Greece
University General Hospital of Larissa
🇬🇷Larissa, Thessaly, Greece
Centro di Riferimento Oncologico di Aviano
🇮🇹Aviano, Pordenone, Italy
Centrul de oncologie Euroclinic
🇷🇴Iasi, Romania
Opca bolnica Dubrovnik
🇭🇷Dubrovnik, Dubrovnik-Neretva, Croatia
Iaso General Hospital
🇬🇷Cholargos, Attica, Greece
Princess Margaret Hospital
🇭🇰Kowloon, Hong Kong
King Chulalongkorn Memorial Hospital
🇹🇭Bangkok, Bangkok Metropolis, Thailand
Kaohsiung Medical University Hospital
🇨🇳Kaohsiung, Taiwan
Institutul Oncologic Prof. Dr. Alexandru Trestioreanu Bucaresti
🇷🇴Bucuresti, Romania
Hualien Tzu Chi Hospital
🇨🇳Hualien City, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Chi Mei Hospital Liouying
🇨🇳Tainan City, Taiwan
Phramongkutklao Hospital
🇹🇭Bangkok, Bangkok Metropolis, Thailand
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Chungbuk National University Hospital
🇰🇷Cheongju-si, Chungcheongbuk-do, Korea, Republic of
Ajou University Hospital
🇰🇷Suwon, Gyeonggi-do, Korea, Republic of
University Cancer and Blood Center
🇺🇸Athens, Georgia, United States
New York Oncology Hematology - Albany Medical Center
🇺🇸Albany, New York, United States
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Tianjin Medical University Cancer Institute & Hospital
🇨🇳Tianjin, Tianjin, China
Hopital Foch
🇫🇷Suresnes, Ile-de-france, France
Fudan University Shanghai Cancer Center
🇫🇷Creteil, Ile-de-france, France
Hopital Haut-Leveque
🇫🇷Pessac, Aquitaine, France
Gustave Roussy
🇫🇷Villejuif cedex, Ile-de-france, France
Centre Hospitalier Intercommunal Toulon - La Seyne Sur Mer
🇫🇷Toulon, Provence Alpes COTE D'azur, France
Centre Hospitalier Universitaire de Toulouse- Hopital Larrey
🇫🇷Toulouse Cedex 9, Midi-pyrenees, France
Centre Hospitalier Le Mans
🇫🇷Le Mans Cedex 9, PAYS DE LA Loire, France
Klinikum Kempten-Oberallgau
🇩🇪Immenstadt, Bayern, Germany
University General Hospital of Athens Attikon
🇬🇷Athens, Attica, Greece
Sotiria General Hospital for Respiratory Diseases of Attica
🇬🇷Athens, Greece
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
🇮🇹Meldola, Forli-cesena, Italy
Azienda Ospedaliera Universitaria San Martino
🇮🇹Genova, Italy
Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi
🇮🇹Bologna, Italy
Istituto Scientifico Universitario San Raffaele
🇮🇹Milano, Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale
🇮🇹Napoli, Italy
Ospedale Santa Maria delle Croci
🇮🇹Ravenna, Italy
National Cancer Center
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
The Catholic University of Korea St. Vincent's Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Gyeonggi-do, Korea, Republic of
Ulsan University Hospital
🇰🇷Ulsan, Gyeongsangnam-do, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea - Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Oncocenter- Oncologie Clinica
🇷🇴Timisoara, Timis, Romania
State Institution of Healthcare Arkhangelsk Regional Clinical Oncology Dispensary
🇷🇺Arkhangelsk, Arkhangelr, Russian Federation
Euromedservice
🇷🇺Saint-Petersburg, Saint Petersburg, Russian Federation
Saint Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Aid
🇷🇺Saint-Petersburg, Saint Petersburg, Russian Federation
Irkutsk Regional Oncology Center
🇷🇺Irkutsk, Russian Federation
Clinica Ultra Sound Diagnostic 4D
🇷🇺Pyatigorsk, Stavropol, Russian Federation
VitaMed
🇷🇺Moscow, Russian Federation
N.N. Blokhin Russian Cancer Research Center
🇷🇺Moscow, Russian Federation
State Budget Institution National Medical Research Center of Radiology of the Ministry of Heal
🇷🇺Moscow, Russian Federation
Moscow City Oncology Hospital Number 62
🇷🇺Moscow, Russian Federation
Omsk Regional Clinical Oncologic Dispensary
🇷🇺Omsk, Russian Federation
Saint Petersburg State Healthcare Institution Municipal Clinical Oncology Dispensary
🇷🇺Saint Petersburg, Russian Federation
Leningrad Regional Clinical Hospital
🇷🇺Saint Petersburg, Russian Federation
Center of Palliative Medicine - Devita
🇷🇺Saint Petersburg, Russian Federation
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital Teresa Herrera - Materno Infantil
🇪🇸A Coruna, LA Coruna, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Toronto University Health Network
🇨🇦Toronto, Ontario, Canada
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Queen Elizabeth II Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
Pamela Youde Nethersole Eastern Hospital
🇭🇰Chai Wan, Eastern District, Hong Kong
Hong Kong United Oncology Centre
🇭🇰Kowloon, Hong Kong