Clinical trial NCT03535740: A Study of Brigatinib in Participants With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib
Official title: Brigatinib in Patients With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: ALK-positive Advanced NSCLC
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Takeda
First posted: 2018-05-24
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to determine the efficacy of brigatinib by confirmed objective response rate (ORR) by response evaluation criteria in solid tumors (Response Evaluation Criteria in Solid Tumors \[RECIST\]), in participants with ALK+ locally advanced or metastatic NSCLC whose disease has progressed on therapy with alectinib or ceritinib.

Detailed description: The drug being tested in this study is called brigatinib (AP26113). Brigatinib is being tested to treat people who have anaplastic lymphoma kinase-positive (ALK+), advanced non-small-cell lung cancer (NSCLC).

The study will enroll approximately 103 patients. Participants will be assigned to the treatment group:

• Brigatinib

All participants will be asked to take brigatinib 90 mg tablet in lead-in period for 7 days, followed by brigatinib 180 mg at the same time each day throughout the study. Participants with progressive disease had an option to receive an escalated dose of brigatinib 240 mg as per investigator's discretion in case no toxicities (greater than grade 2) are experienced.

This multicenter trial will be conducted worldwide. The overall time to participate in this study is approximately 3 years. Participants will make multiple visits to the clinic, and 30 days after last dose of study drug for a follow-up assessment.

Eligibility criteria: Inclusion Criteria:

1. Have histologically or cytologically confirmed stage IIIB (locally advanced or recurrent and not a participant for curative therapy) or stage IV non-small-cell lung cancer (NSCLC).
2. Must meet both of the following 2 criteria:

   1. Have documentation of anaplastic lymphoma kinase (ALK) rearrangement by a positive result from any laboratory test® approved by the food and drug administration (FDA) or Have documented ALK rearrangement by a different test (non-FDA-approved local lab tests) and have provided tumor sample to the central laboratory. (Note: Central laboratory ALK rearrangement testing results are not required to be obtained before randomization.)
   2. Had been on any one of the ALK tyrosine kinase inhibitor (TKIs) (alectinib, ceritinib, crizotinib) for at least 12 weeks before progression.
3. Had progressive disease (PD) while on alectinib or ceritinib
4. Had alectinib or ceritinib as the most recent ALK inhibitor therapy.
5. Have at least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) version 1.1 as assessed by the investigator.
6. Had recovered from toxicities related to prior anticancer therapy to national cancer institute common terminology criteria for adverse events (NCI CTCAE), version 4.03, Grade \<=1. (Note: Treatment-related alopecia or peripheral neuropathy that are Grade \>1 are allowed if deemed irreversible.) and have adequate major organ functions.
7. Have a life expectancy of ≥3 months.

Exclusion Criteria:

1. Had received any prior ALK-targeted TKI other than crizotinib, alectinib, or ceritinib.
2. Had received both alectinib and ceritinib.
3. Had previously received more than 3 regimens of systemic anticancer therapy for locally advanced or metastatic disease.
4. Had symptomatic brain metastasis (parenchymal or leptomeningeal). Participants with asymptomatic brain metastasis or who have stable symptoms that did not require an increased dose of corticosteroids to control symptoms in the past 7 days before the first dose of brigatinib may be enrolled.
5. Had current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Participants with leptomeningeal disease and without cord compression are allowed.
6. Had a cerebrovascular accident or transient ischemic attack within 6 months before first dose of brigatinib.
7. Had an ongoing or active infection, including, but not limited to, the requirement for intravenous antibiotics.
8. Had malabsorption syndrome or other gastrointestinal (GI) illness that could affect oral absorption of brigatinib.

Primary outcomes:
measure: Confirmed Objective Response Rate (ORR) Using RECIST v1.1 as Assessed by the Independent Review Committee (IRC)
timeFrame: Up to approximately 20 months from the start of enrollment till data cut-off 30 September 2020
Secondary outcomes:
measure: Confirmed ORR Using RECIST v1.1 as Assessed by the Investigator
timeFrame: Until the radiological disease progression or study end (approximately 3 years)
measure: Duration of Response (DOR) as Assessed by the Investigator and IRC
timeFrame: Until the radiological disease progression or study end (approximately 3 years)
measure: Progression-Free Survival (PFS) as Assessed by the Investigator and IRC
timeFrame: Until the radiological disease progression or study end (approximately 3 years)
measure: Disease Control Rate (DCR) as Assessed by the Investigator and IRC
timeFrame: Until the radiological disease progression or study end (approximately 3 years)
measure: Time to Response as Assessed by the Investigator and IRC
timeFrame: Until the radiological disease progression or study end (approximately 3 years)
measure: Confirmed Intracranial Objective Response Rate (iORR) in Participants With Brain Metastases at Baseline, as Assessed by the IRC
timeFrame: Until the radiological disease progression or study end (approximately 3 years)
measure: Duration of Intracranial Response in Participants With Brain Metastases at Baseline, as Assessed by the IRC
timeFrame: Until the radiological disease progression or study end (approximately 3 years)
measure: Intracranial Progression-Free Survival (iPFS) in Participants With Brain Metastases at Baseline, as Assessed by the IRC
timeFrame: Until the radiological disease progression or study end (approximately 3 years)
measure: Overall Survival (OS)
timeFrame: Until the radiological disease progression or study end (approximately 3 years)
measure: Number of Participants With One or More Treatment-emergent Adverse Event (TEAE)
timeFrame: First dose of study drug up to 30 days after last dose (approximately 3 years)
measure: Health-Related Quality of Life (HRQOL) From European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score
timeFrame: First dose of study drug up to 30 days after last dose (approximately 3 years)
measure: HRQOL From EORTC QLQ- Lung Cancer (LC) 13
timeFrame: First dose of study drug up to 30 days after last dose (approximately 3 years)
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine Health Chao Family Comprehensive Cancer Center
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation
state: California
city: Pueblo
country: United States
facility: USOR - Rocky Mountain Cancer Centers - Pueblo
state: Colorado
city: Orlando
country: United States
facility: Florida Hospital Medical Group
state: Florida
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Charlotte
country: United States
facility: Levine Cancer Institute - Southpark
state: North Carolina
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Fairfax
country: United States
facility: USOR - Virginia Cancer Specialists - Fairfax Office
state: Virginia
city: Fitzroy
country: Australia
facility: Saint Vincent's Hospital Melbourne
state: Victoria
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology and Oncology Group
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Klagenfurt
country: Austria
facility: Klinikum Klagenfurt Am Worthersee
state: Carinthia
city: Linz
country: Austria
facility: Krankenhaus Elisabethinen Linz
state: Upper Austria
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
state: British Columbia
city: Toronto
country: Canada
facility: Toronto University Health Network
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Changchun
country: China
facility: Jilin Provincial Cancer Hospital (Changchun Cancer Hospital)
state: Jilin
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Pessac
country: France
facility: Hopital Haut-Leveque
state: Aquitaine
city: Creteil
country: France
facility: Centre Hospitalier Intercommunal de Creteil
state: Ile-de-france
city: Toulouse Cedex 9
country: France
facility: Hopital Larrey, CHU de Toulouse, Service de Pneumologie
state: Midi-pyrenees
city: Marseille
country: France
facility: Assistance Publique-Hopitaux de Marseille Hopital Nord
state: Provence Alpes COTE D'azur
city: Lyon
country: France
facility: Centre de Lutte Contre le Cancer Centre Leon Berard
state: Rhone-alpes
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH
state: Baden-wuerttemberg
city: Ulm
country: Germany
facility: Universitatsklinikum Ulm
state: Baden-wuerttemberg
city: Kempten
country: Germany
facility: Klinikum Kempten-Oberallgau
state: Bavaria
city: Munchen
country: Germany
facility: Ludwig-Maximilians-Universitat Munchen
state: Bayern
city: Oldenburg
country: Germany
facility: Pius Hospital Oldenburg
state: Niedersachsen
city: Hamm
country: Germany
facility: Evangelisches Krankenhaus Hamm
state: Nordrhein-westfalen
city: Berlin
country: Germany
facility: HELIOS Klinikum Emil von Behring
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
state: New Territories
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Kowloon
country: Hong Kong
facility: Queen Elizabeth Hospital
city: Kowloon
country: Hong Kong
facility: Princess Margaret Hospital - Hong Kong
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
state: Lazio
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico di Aviano
state: Pordenone
city: Orbassano
country: Italy
facility: Azienda Ospedaliero - Universitaria San Luigi Gonzaga
state: Torino
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Ravenna
country: Italy
facility: Azienda USL della Romagna
city: Toyoake
country: Japan
facility: Fujita Health University Hospital
state: Aichi
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Sendai
country: Japan
facility: Sendai Kousei Hospital
state: Miyagi
city: Okayama-city
country: Japan
facility: Okayama University Hospital
state: Okayama
city: Hirakata-shi
country: Japan
facility: Kansai Medical University Hirakata Hospital
state: Osaka
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
state: Tokyo
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
state: Gyeonggi-do
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Gyeongsangbuk-do
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
state: Limburg
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum
state: Noord-holland
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center
state: Zuid-holland
city: Badalona
country: Spain
facility: Institut Catala d'Oncologia Badalona - Hospital Germans Trias i Pujol
state: Barcelona
city: A Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruna
state: LA Coruna
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Ramon Y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
city: Lund
country: Sweden
facility: Skanes Universitetssjukhus i Lund
state: Skane
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset
city: Uppsala
country: Sweden
facility: Uppsala Akademiska Sjukhus
city: Changhua City
country: Taiwan
facility: Changhua Christian Hospital
state: Changhwa
city: Tainan
country: Taiwan
facility: National Cheng Kung University
state: Tainan CITY
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Kim ES, Barlesi F, Mok T, Ahn MJ, Shen J, Zhang P, Ou SI. ALTA-2: Phase II study of brigatinib in patients with ALK-positive, advanced non-small-cell lung cancer who progressed on alectinib or ceritinib. Future Oncol. 2021 May;17(14):1709-1719. doi: 10.2217/fon-2020-1119. Epub 2021 Feb 11.