Description:
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.
Title
- Brief Title: A Study of Brigatinib Compared to Alectinib in Adults With Non-Small-Cell Lung Cancer
- 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®)
Clinical Trial IDs
- ORG STUDY ID:
Brigatinib-3001
- SECONDARY ID:
2018-001957-29
- NCT ID:
NCT03596866
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Brigatinib | Alunbrig | Brigatinib |
Alectinib | Alecensa | Alectinib |
Purpose
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 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 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.
Trial Arms
Name | Type | Description | Interventions |
---|
Brigatinib | Experimental | 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. | |
Alectinib | Active Comparator | Alectinib 600 mg, capsules, orally twice daily until objective disease progression per RECIST version 1.1, as assessed by the investigator, or intolerable toxicity. | |
Eligibility 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 before 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. 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 patients with another primary malignancy who
are definitively relapse-free with at least 3 years elapsed since the diagnosis of the
other primary malignancy.
8. Had received chemotherapy or radiation therapy within 14 days before randomization
except for stereotactic radiosurgery (SRS) or stereotactic body radiation therapy.
9. Had received antineoplastic monoclonal antibodies within 30 days of randomization.
10. Had major surgery within 30 days of randomization. Minor surgical procedures, such as
catheter placement or minimally invasive biopsies, are allowed.
11. 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.
12. Have current spinal cord compression (symptomatic or asymptomatic and detected by
radiographic imaging). Participants with leptomeningeal disease and without cord
compression are allowed.
13. 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.
14. Had cerebrovascular accident or transient ischemic attack within 6 months before first
dose of study drug.
15. Have malabsorption syndrome or other gastrointestinal illness or condition that could
affect oral absorption of the study drug.
16. Have an ongoing or active infection, including but not limited to, the requirement for
intravenous antibiotics.
17. Have a known history of human immunodeficiency virus (HIV) infection. Testing is not
required in the absence of history.
18. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C
infection. Testing is not required in the absence of history.
19. Any serious medical condition or psychiatric illness that could, in the investigator's
opinion, potentially compromise patient safety or interfere with the completion of
treatment according to this protocol.
20. Have a known or suspected hypersensitivity to brigatinib or alectinib or their
excipients.
21. Life-threatening illness unrelated to cancer.
22. Female patients who are lactating and breastfeeding.
23. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | PFS as Assessed by Blinded Independent Review Committee (BIRC) per RECIST v1.1 |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | 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
Measure: | Overall Survival (OS) |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | 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. |
Measure: | PFS as Assessed by Investigator per RECIST v1.1 |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | 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. |
Measure: | Objective Response Rate (ORR) as Assessed by Investigator and BIRC per RECIST v1.1 |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | 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. |
Measure: | Duration of Response (DOR) as Assessed by Investigator and BIRC |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | 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. |
Measure: | Time to Response as Assessed by Investigator and BIRC |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | 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. |
Measure: | Intracranial Objective Response Rate (iORR) as Assessed by BIRC per Modified RECIST v1.1 |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | 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. |
Measure: | Intracranial Duration of Response (iDOR) as Assessed by the BIRC per Modified RECIST v1.1 |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | 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. |
Measure: | Time to Intracranial Disease Progression (iPD) as Assessed by BIRC per Modified RECIST v1.1 |
Time Frame: | Up to 5 years |
Safety Issue: | |
Description: | 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. |
Measure: | 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 5 years) |
Safety Issue: | |
Description: | 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. |
Measure: | HRQOL from EORTC QLQ- Lung Cancer (LC) 13 |
Time Frame: | First dose of study drug up to 30 days after last dose (approximately 5 years) |
Safety Issue: | |
Description: | 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. |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Takeda |
Trial Keywords
Last Updated
April 22, 2021