A Study of Brigatinib in Participants With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib

ALK-positive Advanced NSCLC Clinical Trial

— ALTA-2  

Official title:

Brigatinib in Patients With Anaplastic Lymphoma Kinase-Positive (ALK+), Advanced Non-Small-Cell Lung Cancer (NSCLC) Progressed on Alectinib or Ceritinib

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03535740
• Other study ID #: Brigatinib-2002
• Secondary ID: 2018-000635-27NL
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 31, 2019
• Est. completion date: June 28, 2024

Study information

• Verified date: August 2023
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 103
• Est. completion date: June 28, 2024
• Est. primary completion date: September 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• ALK-positive Advanced NSCLC
• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Brigatinib
Brigatinib Tablets

Locations

Country	Name	City	State
Australia	Saint Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Peninsula & South Eastern Haematology and Oncology Group	Frankston	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Austria	Klinikum Klagenfurt Am Worthersee	Klagenfurt	Carinthia
Austria	Krankenhaus Elisabethinen Linz	Linz	Upper Austria
Canada	Tom Baker Cancer Center	Calgary	British Columbia
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	McGill University Health Centre	Montreal	Quebec
Canada	Toronto University Health Network	Toronto	Ontario
China	Beijing Cancer Hospital	Beijing	Beijing
China	Jilin Provincial Cancer Hospital (Changchun Cancer Hospital)	Changchun	Jilin
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Shanghai Pulmonary Hospital	Shanghai	Shanghai
France	Centre Hospitalier Intercommunal de Creteil	Creteil	Ile-de-france
France	Centre de Lutte Contre le Cancer Centre Leon Berard	Lyon	Rhone-alpes
France	Assistance Publique-Hopitaux de Marseille Hopital Nord	Marseille	Provence Alpes COTE D'azur
France	Hopital Haut-Leveque	Pessac	Aquitaine
France	Hopital Larrey, CHU de Toulouse, Service de Pneumologie	Toulouse Cedex 9	Midi-pyrenees
Germany	HELIOS Klinikum Emil von Behring	Berlin
Germany	Evangelisches Krankenhaus Hamm	Hamm	Nordrhein-westfalen
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg	Baden-wuerttemberg
Germany	Klinikum Kempten-Oberallgau	Kempten	Bavaria
Germany	Ludwig-Maximilians-Universitat Munchen	Munchen	Bayern
Germany	Pius Hospital Oldenburg	Oldenburg	Niedersachsen
Germany	Universitatsklinikum Ulm	Ulm	Baden-wuerttemberg
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Princess Margaret Hospital - Hong Kong	Kowloon
Hong Kong	Queen Elizabeth Hospital	Kowloon
Hong Kong	Prince of Wales Hospital	Shatin	New Territories
Italy	Centro di Riferimento Oncologico di Aviano	Aviano	Pordenone
Italy	Istituto Europeo di Oncologia	Milano
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale	Napoli
Italy	Azienda Ospedaliero - Universitaria San Luigi Gonzaga	Orbassano	Torino
Italy	Azienda Ospedaliero Universitaria di Parma	Parma
Italy	Azienda USL della Romagna	Ravenna
Italy	Azienda Ospedaliera San Camillo Forlanini	Roma	Lazio
Japan	Kansai Medical University Hirakata Hospital	Hirakata-shi	Osaka
Japan	The Cancer Institute Hospital of Japanese Foundation for Cancer Research	Koto-ku	Tokyo
Japan	Okayama University Hospital	Okayama-city	Okayama
Japan	Sendai Kousei Hospital	Sendai	Miyagi
Japan	Fujita Health University Hospital	Toyoake	Aichi
Japan	Kanagawa Cancer Center	Yokohama	Kanagawa
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si	Gyeongsangbuk-do
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul	Gyeonggi-do
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital	Seoul
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam	Noord-holland
Netherlands	Maastricht University Medical Centre	Maastricht	Limburg
Netherlands	Erasmus University Medical Center	Rotterdam	Zuid-holland
Spain	Complejo Hospitalario Universitario A Coruna	A Coruna	LA Coruna
Spain	Institut Catala d'Oncologia Badalona - Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Madrid
Spain	Hospital Universitario Ramon Y Cajal	Madrid
Sweden	Skanes Universitetssjukhus i Lund	Lund	Skane
Sweden	Karolinska Universitetssjukhuset	Stockholm
Sweden	Uppsala Akademiska Sjukhus	Uppsala
Taiwan	Changhua Christian Hospital	Changhua City	Changhwa
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University	Tainan	Tainan CITY
United States	Levine Cancer Institute - Southpark	Charlotte	North Carolina
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	USOR - Virginia Cancer Specialists - Fairfax Office	Fairfax	Virginia
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	University of California Irvine Health Chao Family Comprehensive Cancer Center	Orange	California
United States	Florida Hospital Medical Group	Orlando	Florida
United States	Providence Portland Medical Center	Portland	Oregon
United States	USOR - Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	The Oncology Institute of Hope and Innovation	Whittier	California

Sponsors (2)

Lead Sponsor	Collaborator
Ariad Pharmaceuticals	Takeda

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  China,  France,  Germany,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Sweden,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed Objective Response Rate (ORR) Using RECIST v1.1 as Assessed by the Independent Review Committee (IRC)	Confirmed ORR is defined as the percentage of the participants who are confirmed to have achieved complete response (CR) or partial response (PR), per RECIST version 1.1 (confirmed =4 weeks after initial response), after the initiation of study treatment. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis and PR: at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions taking as reference the Baseline sum diameters.	Up to approximately 20 months from the start of enrollment till data cut-off 30 September 2020
Secondary	Confirmed ORR Using RECIST v1.1 as Assessed by the Investigator	Confirmed ORR is defined as the percentage of the participants who are confirmed to have achieved CR or PR, per RECIST version 1.1 (confirmed =4 weeks after initial response), after the initiation of study treatment. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis and PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters.	Until the radiological disease progression or study end (approximately 3 years)
Secondary	Duration of Response (DOR) as Assessed by the Investigator and IRC	DOR is defined as the time interval from the time that the measurement criteria are first met for CR or PR until the first date that the progressive disease (PD) is objectively documented, or death. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. PR: at least a 30% decrease in the SLD of target lesions taking as reference the Baseline sum diameters. PD: 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).	Until the radiological disease progression or study end (approximately 3 years)
Secondary	Progression-Free Survival (PFS) as Assessed by the Investigator and IRC	PFS is defined as the time interval from the date of the first dose of the study treatment until the first date at which disease progression is objectively documented, or death due to any cause, whichever occurs first. PFS will be censored for participants without documented disease progression or death.	Until the radiological disease progression or study end (approximately 3 years)
Secondary	Disease Control Rate (DCR) as Assessed by the Investigator and IRC	DCR is defined as the percentage of participants who have achieved CR, PR or stable disease (SD) (in the case of SD, measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks) after the initiation of study treatment. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.	Until the radiological disease progression or study end (approximately 3 years)
Secondary	Time to Response as Assessed by the Investigator and IRC	Time to response is defined as the time interval from the date of the first dose of the study treatment until the initial observation of CR or PR. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters.	Until the radiological disease progression or study end (approximately 3 years)
Secondary	Confirmed Intracranial Objective Response Rate (iORR) in Participants With Brain Metastases at Baseline, as Assessed by the IRC	Confirmed iORR is defined as the proportion of the participants who have achieved CR or PR in the brain per a modification of RECIST version 1.1, after the initiation of study treatment, in participants with intracranial brain metastases at baseline. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. or partial response or PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters.	Until the radiological disease progression or study end (approximately 3 years)
Secondary	Duration of Intracranial Response in Participants With Brain Metastases at Baseline, as Assessed by the IRC	Duration of intracranial response is defined as the time interval from the time that the measurement criteria are first met for CR or PR until the first date that PD (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) in the brain is objectively documented or death, in participants with intracranial metastases at baseline. CR: disappearance of all extranodal target lesions and all pathological lymph nodes must have decreased to <10 mm in short axis. or partial response or PR: at least a 30% decrease in the SLD of target lesions taking as reference the baseline sum diameters in the brain. PD: SLD increased by at least 20% from the smallest value on study.	Until the radiological disease progression or study end (approximately 3 years)
Secondary	Intracranial Progression-Free Survival (iPFS) in Participants With Brain Metastases at Baseline, as Assessed by the IRC	iPFS is defined as the time interval from the date of the first dose of the study treatment until the first date at which intracranial brain disease progression is objectively documented, or death due to any cause, whichever occurs first, in participants with intracranial metastases at enrollment. iPFS will be censored for participants without documented intracranial disease progression or death.	Until the radiological disease progression or study end (approximately 3 years)
Secondary	Overall Survival (OS)	OS is defined as the time interval from the date of the first dose of the study treatment until death due to any cause. It will be censored on the date of last contact for those participants who are alive.	Until the radiological disease progression or study end (approximately 3 years)
Secondary	Number of Participants With One or More Treatment-emergent Adverse Event (TEAE)	An adverse event (AE) means any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug.	First dose of study drug up to 30 days after last dose (approximately 3 years)
Secondary	Health-Related Quality of Life (HRQOL) From European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score	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.	First dose of study drug up to 30 days after last dose (approximately 3 years)
Secondary	HRQOL From EORTC QLQ- Lung Cancer (LC) 13	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.	First dose of study drug up to 30 days after last dose (approximately 3 years)