Non-Small Cell Lung CancerPhase 2NCT02706626
Trial of Brigatinib After Treatment With Next-Generation ALK Inhibitors
A Phase 2 study testing brigatinib in people with Non-Small Cell Lung Cancer, run by Criterium, Inc. at 4 sites in United States.
Trial summary
The purpose of this study is to evaluate the safety and effectiveness of this investigational drug, brigatinib (AP261136) in patients with advanced non-small cell lung cancer Non-small cell lung cancer (NSCLC) who have had first-line treatment for their cancer and it still got worse, even after, or while taking drugs… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- brigatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 4 sitesUnited States
- Study dates
- 9 Mar 2017to 1 Apr 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Locally advanced or metastatic NSCLC that has been cytologically or histologically confirmed
- ALK rearrangement based on FDA approved test (e.g. Vysis breakapart FISH or IHC using Ventana)
- ECOG PS ≤2
- Age of ≥ 18 years
- Brain lesions may be used as target lesions if progressing, ≥10mm in longest diameter and if they were not previously treated with any of the following:
- Whole brain radiation therapy (WBRT) within 3 months
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- Stereotactic radiosurgery (SRS)
- Surgical resection Availability of core biopsy of progressive lesion taken within 60 days prior to D1 of treatment under study therapy or willing to undergo tumor biopsy: NOTE:. All subjects must consent to provide tumor blocks or slides.
- If archival tissue is not available and biopsies to obtain fresh tumor tissue cannot be performed with minimal risk to the subject, subjects may be permitted to enroll on the study with prior approval of the Study PI.
- In the situation the patient undergoes biopsy within 60 days prior to D1. and there is insufficient tumor tissue subjects for the correlative science part of the protocol patient will be permitted to enroll on the study with prior approval of the study PI
- In the situation the patient undergoes molecular testing or next-generation sequencing as part of standard care there must be sufficient tumor sample available for participation in the study (i.e. a next generation sequencing report is not sufficient for enrollment)
- Recovered from toxicities related to prior anticancer treatment to ≤Grade 2 or baseline with the exception of alopecia
- Have normal QT interval on ECG evaluation QT corrected Fridericia (QTcF) of ≤ 450 ms in males or ≤ 470 ms in females
- Adequate organ function defined as:
- Absolute neutrophil count (ANC) ≥1500/µL Platelets ≥75,000/µL Hemoglobin≥ 10g/dL AST /ALT ≤ 2.5 x upper limit of normal (ULN); ≤ 5 x ULN if liver metastasis Total serum bilirubin ≤ 1.5 x ULN Serum creatinine ≤ 1.5 x UNL Serum amylase ≤ 1.5 x UNL
- At least 1 measurable lesion per RECIST version 1.1
- Negative serum pregnancy test within 7 days of D1 of treatment in women of child bearing potential (WOCBP)
- If fertile, willing to use highly effective form of contraception (defined as a combination of at least two of the following methods: condom or other barrier methods, oral contraceptives, implantable contraceptives, intrauterine devices) during the dosing period and for at least 4 months after
- Ability to provide signed informed consent and willing and able to comply with all study requirements
- Cohort A: Progressive disease on any next generation ALK inhibitor except first line alectinib or brigatinib (any line)
- Cohort B: Progressive disease on first-line therapy with alectinib, and no other ALK inhibitors
- Cohort C: Previous treatment brigatinib at 180 mg daily for ≥4 weeks without > grade 2 drug-related toxicities and with radiographic evidence of progressive disease and no intervening systemic therapies such as chemotherapy, immunotherapy or another ALK inhibitor (radiation therapy allowed as intervening therapy). Patients who are treated on cohorts A and B will be allowed to enroll in cohort C if the meet the inclusion and exclusion criteria
Who cannot join
- Patients meeting any of the following exclusion criteria will not be able to participate in this study:
- History or the presence of pulmonary interstitial disease, drug-related or immune-related pneumonitis, or radiation pneumonitis requiring medical management within 6 months of trial enrollment
- Prior treatment with brigatinib for cohorts A and B
- History of or active significant gastrointestinal (GI) bleeding within 3 months
- Malabsorption syndrome or other GI illness that could affect oral absorption of the study drug
- Received cytotoxic chemotherapy, investigational agents or radiation within 7 days prior to D1 of study treatment
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- Received prior ALK TKI therapy within 7 days prior to D1 of treatment under study drug. 7 day wash out period is required after prior ALK inhibitor treatment.
- Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
- Myocardial infarction (MI) within 6 months of trial enrollment
- Unstable angina within 6 months of trial enrollment
- Congestive heart failure (CHF) with 6 months prior to trial enrollment
- Any history of ventricular arrhythmia
- Cerebrovascular accident or transient ischemic attack within 6 months of D1 of study treatment
- Clinically significant atrial arrhythmia or severe baseline bradycardia defined as resting heart rate < 60 beat per minute
- Uncontrolled hypertension defined as baseline SBP> 160 and DBP > 100 on 3 separate clinic visits or past history of hypertensive urgency, emergency or encephalopathy
- Have been diagnosed with another primary malignancy within the past 3 years (except for adequately treated non-melanoma skin cancer, cervical cancer in situ, or prostate cancer, which are allowed within 3 years)
- Have symptomatic CNS metastases which require an increasing dose of corticosteroids within the last 2 weeks to remain asymptomatic.
- Have active infection requiring intravenous antibiotics
- Pregnant or breastfeeding
- Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with evaluation of the study drug.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
University of Texas, Southwestern
Dallas, Texas, 75390
University Of Colorado
Denver, Colorado, 80045
Duke University
Durham, North Carolina, 27710
Vanderbilt Unversity Medical Center
Nashville, Tennessee, 37203
About this study
Official title: Phase 2 Trial of Brigatinib After Treatment With Next-Generation ALK Inhibitors in Refractory ALK Rearranged Non-Small Cell Lung Cancer (NSCLC)
The purpose of this study is to evaluate the safety and effectiveness of this investigational drug, brigatinib (AP261136) in patients with advanced non-small cell lung cancer Non-small cell lung cancer (NSCLC) who have had first-line treatment for their cancer and it still got worse, even after, or while taking drugs called ALK inhibitors, or anti-cancer drugs that act on tumors. Some examples of these anti-cancer drugs are: KEYTRUDA® or ALECENSA®).
Read the detailed description
A significant population of Anaplastic Lymphoma Kinase (ALK) plus Non-small cell lung cancer patients exist that have progressed on or who were intolerant of second generation anaplastic lymphoma kinase inhibitor (e.g. ceritinib or alectinib). Brigatinib has demonstrated activity in patients who have progressed on crizotinib, but the activity of brigatinib in patients who have progressed on ceritinib, alectinib, or other second generation anaplastic lymphoma kinase inhibitors is unknown. Based on the preclinical data. 3, , brigatinib has activity against known secondary anaplastic lymphoma kinase mutations suggesting it may retain activity after second-generation anaplastic lymphoma kinase inhibitors.
Patients enrolled in ARI-AT-002 must have previously received a second generation Anaplastic lymphoma kinase inhibitor other than brigatinib. We have chosen 20% as a clinically meaningful response rate that would justify further study of brigatinib in previously treated anaplastic lymphoma kinase plus disease.
- Conditions
- Non-Small Cell Lung Cancer
- Being tested
- brigatinib
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
brigatinibDrug
Also called AP26113
Single arm phase 2 trial to investigate the clinical activity in patients with advanced non-small cell lung cancer
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: Disease progression after next generation ALK TKI | Experimental | Brigatinib until progressive disease, unacceptable toxicity, withdrawal of consent. Patients enrolled regardless the number of lines of therapy Receives: Drug: brigatinib |
| Cohort B: Disease progression after alectinib as first-line therapy | Experimental | Brigatinib until progressive disease, unacceptable toxicity, withdrawal of consent. Patients enrolled after first-line alectinib Receives: Drug: brigatinib |
| Cohort C: Disease progression after brigatinib | Experimental | Brigatinib at 240 mg daily until progressive disease, unacceptable toxicity, withdrawal of consent. Patients enrolled after treatment on brigatinib at the standard dose brigatinib Receives: Drug: brigatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
An assessment of the response using RECIST 1.1 per investigator. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.". The enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results
Measured: Through study completion (average 42 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2016 (estimated)
- Study start9 Mar 2017
- Primary completion8 Oct 2020
- Study completion1 Apr 2021
Why it stopped: Did not meet enrollment objectives.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Criterium, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Colorado, Denver, Duke University, Takeda, Vanderbilt University, University of Texas Southwestern Medical Center, University of Pittsburgh, Ohio State University, Georgetown University, Academic Thoracic Oncology Medical Investigators Consortium
- Responsible party
- Sponsor
- Investigators
- Thomas Stinchcombe, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02706626
- Sponsor's protocol ID
- ARI-AT-002
- Status last verified
- Jan 2023
- First submitted
- 8 Mar 2016
- Last updated
- 26 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stinchcombe TE, Doebele RC, Wang X, Gerber DE, Horn L, Camidge DR. Preliminary Clinical and Molecular Analysis Results From a Single-Arm Phase 2 Trial of Brigatinib in Patients With Disease Progression After Next-Generation ALK Tyrosine Kinase Inhibitors in Advanced ALK+ NSCLC. J Thorac Oncol. 2021 Jan;16(1):156-161. doi: 10.1016/j.jtho.2020.09.018. Epub 2020 Oct 8.
PubMed 33039599
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Trial of Brigatinib After Treatment With Next-Generation ALK Inhibitors in Refractory ALK Rearranged Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT02706626
- Acronym / sponsor ID
- ARI-AT-002
- Conditions
- Non-Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Did not meet enrollment objectives.
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Criterium, Inc.Industry (pharma, biotech, devices)
- Collaborators
- University of Colorado, Denver, Duke University, Takeda, Vanderbilt University, University of Texas Southwestern Medical Center, University of Pittsburgh, Ohio State University, Georgetown University, Academic Thoracic Oncology Medical Investigators Consortium
- Study start
- 9 Mar 2017 (actual)
- Primary completion
- 8 Oct 2020 (actual)
- Study completion
- 1 Apr 2021 (actual)
- First posted
- 11 Mar 2016 (estimated)
- Results
- Posted 26 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and effectiveness of this investigational drug, brigatinib (AP261136) in patients with advanced non-small cell lung cancer Non-small cell lung cancer (NSCLC) who have had first-line treatment for their cancer and it still got worse, even after, or while taking drugs called ALK inhibitors, or anti-cancer drugs that act on tumors. Some examples of these anti-cancer drugs are: KEYTRUDA® or ALECENSA®).
Detailed description
A significant population of Anaplastic Lymphoma Kinase (ALK) plus Non-small cell lung cancer patients exist that have progressed on or who were intolerant of second generation anaplastic lymphoma kinase inhibitor (e.g. ceritinib or alectinib). Brigatinib has demonstrated activity in patients who have progressed on crizotinib, but the activity of brigatinib in patients who have progressed on ceritinib, alectinib, or other second generation anaplastic lymphoma kinase inhibitors is unknown. Based on the preclinical data. 3, , brigatinib has activity against known secondary anaplastic lymphoma kinase mutations suggesting it may retain activity after second-generation anaplastic lymphoma kinase inhibitors.
Patients enrolled in ARI-AT-002 must have previously received a second generation Anaplastic lymphoma kinase inhibitor other than brigatinib. We have chosen 20% as a clinically meaningful response rate that would justify further study of brigatinib in previously treated anaplastic lymphoma kinase plus disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A: Disease progression after next generation ALK TKI | Experimental | Drug: brigatinibBrigatinib until progressive disease, unacceptable toxicity, withdrawal of consent. Patients enrolled regardless the number of lines of therapy |
| Cohort B: Disease progression after alectinib as first-line therapy | Experimental | Drug: brigatinibBrigatinib until progressive disease, unacceptable toxicity, withdrawal of consent. Patients enrolled after first-line alectinib |
| Cohort C: Disease progression after brigatinib | Experimental | Drug: brigatinibBrigatinib at 240 mg daily until progressive disease, unacceptable toxicity, withdrawal of consent. Patients enrolled after treatment on brigatinib at the standard dose brigatinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Locally advanced or metastatic NSCLC that has been cytologically or histologically confirmed
- ALK rearrangement based on FDA approved test (e.g. Vysis breakapart FISH or IHC using Ventana)
- ECOG PS ≤2
- Age of ≥ 18 years
- Brain lesions may be used as target lesions if progressing, ≥10mm in longest diameter and if they were not previously treated with any of the following:
Key exclusion criteria (20 listed)
- Patients meeting any of the following exclusion criteria will not be able to participate in this study:
- History or the presence of pulmonary interstitial disease, drug-related or immune-related pneumonitis, or radiation pneumonitis requiring medical management within 6 months of trial enrollment
- Prior treatment with brigatinib for cohorts A and B
- History of or active significant gastrointestinal (GI) bleeding within 3 months
- Malabsorption syndrome or other GI illness that could affect oral absorption of the study drug
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| brigatinibAlso: AP26113Single arm phase 2 trial to investigate the clinical activity in patients with advanced non-small cell lung cancer | Drug | Cohort A: Disease progression after next generation ALK TKI, Cohort B: Disease progression after alectinib as first-line therapy, Cohort C: Disease progression after brigatinib |
Primary outcome
Objective Response Rate
Time frame: Through study completion (average 42 months)
An assessment of the response using RECIST 1.1 per investigator. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.". The enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33039599Stinchcombe TE, Doebele RC, Wang X, Gerber DE, Horn L, Camidge DR. Preliminary Clinical and Molecular Analysis Results From a Single-Arm Phase 2 Trial of Brigatinib in Patients With Disease Progression After Next-Generation ALK Tyrosine Kinase Inhibitors in Advanced ALK+ NSCLC. J Thorac Oncol. 2021 Jan;16(1):156-161. doi: 10.1016/j.jtho.2020.09.018. Epub 2020 Oct 8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Stinchcombe, MD principal investigator
Duke University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing brigatinib in people with Non-Small Cell Lung Cancer, run by Criterium, Inc. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: Through study completion (average 42 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02706626, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2023.