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Non-small Cell Lung CancerPhase 2NCT05361564

A Window of Opportunity Study for Investigating Drug Tolerant Persister (DTP) to Preoperative Brigatinib in Resectable Non-small Cell Lung Cancer (NSCLC) Harboring ALK Fusions.

A Phase 2 study testing Brigatinib in people with Non-small Cell Lung Cancer, run by Yonsei University at 1 site in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This study is single arm, open label, phase II trial for resectable ALK+ NSCLC. Eligible patients will receive brigatinib after 7-day lead-in 90mg from 4 to 10 weeks. The objective of this study is as follows. Read more about this study

Who is it for?
Ages 20 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
12 participants
Where
1 siteSouth Korea
Study dates
Jun 2022to Jun 2024
Phase
Phase 2
Are there results?
None posted in the registry

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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients 20 years or older.
  • Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
  • Female patients who:
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
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  • Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or
  • Agree to completely abstain from heterosexual intercourse
  • Treatment-naïve stage I to IIIa non-small cell lung cancer according to the AJCC 8th edition and amenable to surgical resection.
  • Documented ALK rearrangement (VENTANA ALK (D5F3) CDx Assay or appropriate diagnostic method)
  • Brain magnetic resonance imaging (MRI) (or CT if contraindication to MRI) within the last 60 days showing no evidence of metastatic disease
  • Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0 or 1
  • Documentation that the patient is a candidate for surgical resection of their lung cancer by certified surgeon.
  • Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • Clinical laboratory values as specified below within 4 weeks before the first dose of study drug:
  • ALT/aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN); ≤5 × ULN is acceptable if liver metastases are present.
  • Total serum bilirubin ≤1.5 × ULN (<3.0 × ULN for patients with Gilbert syndrome).
  • Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, using the modification of diet in renal disease (MDRD) equationd) Serum lipase ≤1.5 × ULN.
  • Absolute neutrophil count ≥1.5 × 10^9/L.
  • Platelet count ≥75 × 10^9/L.
  • Hemoglobin ≥8 g/dL.
  • Ability to swallow oral medications

Who cannot join

  • Clinical stage IIIb or IIIc or distant metastases (including malignant pleural effusion) identified in CT, PET-CT, brain imaging or biopsy.
  • Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
  • Treatment with any investigational products within 4 weeks before the first dose of study drug
  • Had major surgery within 30 days of the first dose of brigatinib. Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed.
  • 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.
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  • Have symptomatic brain metastasis (parenchymal or leptomeningeal). Patients 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.
  • Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Patients with leptomeningeal disease and without cord compression are allowed.
  • Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
  • Myocardial infarction within 6 months before the first dose of brigatinib.
  • Unstable angina within 6 months before first dose of brigatinib.
  • Congestive heart failure within 6 months before first dose of brigatinib.
  • History of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician.
  • Any history of clinically significant ventricular arrhythmia.
  • Had a cerebrovascular accident or transient ischemic attack within 6 months before first dose of brigatinib.
  • Have uncontrolled hypertension. Patients with hypertension should be under treatment on study entry to control blood pressure.
  • Have a history or the presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis.
  • Have an ongoing or active infection, including, but not limited to, the requirement for intravenous antibiotics.
  • Have a known history of HIV infection. Testing is not required in the absence of history.
  • Have malabsorption syndrome or other GI illness that could affect oral absorption of brigatinib.
  • Have a known or suspected hypersensitivity to brigatinib or its excipients.
  • Are pregnant, planning a pregnancy, or breastfeeding.
  • Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of brigatinib.
  • Received systemic treatment with strong cytochrome P-450 (CYP)3A inhibitors, strong CYP3A inducers, or moderate CYP3A inducers within 14 days before enrollment.

Trial locations and contacts

1 site in 1 country.

Hye Ryun Kim contact

+82-2-2228-8125

nobelg@yuhs.ac

South Korea1 site

  • Yonsei University Health System, Severance Hospital

    Seoul

    Hye Ryun Kim, 82-2-2228-8125, nobelg@yuhs.ac

Other trials in South Korea

About this study

This study is single arm, open label, phase II trial for resectable ALK+ NSCLC. Eligible patients will receive brigatinib after 7-day lead-in 90mg from 4 to 10 weeks.

The objective of this study is as follows.

Read more
  • Primary objective: To identify molecular mechanism of DTP causing innate drug resistance to neoadjuvant brigatinib in resectable NSCLC harboring ALK fusion by analyzing single cell RNA-seq.
  • Secondary objectives:
  1. To assess the pathologic response rate to neoadjuvant treatment with Brigatinib
  2. To evaluate the clinical efficacy in resectable ALK-positive NSCLC patients treated with brigatinib induction therapy
  3. To evaluate the successful curative resection rate
  4. To evaluate the safety of brigatinib as neoadjuvant treatment in resectable ALK-rearranged NSCLC patients.
  5. To investigate the changes of ALK rearrangement and other hot spot mutations by GUARDANT LUNAR assay of circulating tumor DNA present in blood plasma immediately with serial sampling.
  6. To assess of variant allele frequencies between pre-treatment and post-treatment sampling by GUARDANT LUNAR assay
  7. To explore cell-free biomarkers that may be predictive of response or primary resistance to brigatinib neoadjuvant therapy
Read the detailed description

This study is single arm, open label, phase II trial for resectable ALK+ NSCLC. Eligible patients will receive brigatinib after 7-day lead-in 90 mg from 4 to 10 weeks. The surgery with curative intent will be performed within 4 - 10 weeks after initiating brigatinib (optimal duration: 6 weeks). The surgery with curative intent represents more than sublobar resection with mediastinal lymph node dissection. Patients take it up to the day before surgery and can be allow stop up to 3 days before surgery by physician's discretion.

Post-operative adjuvant treatment will be conducted based on the treating physician's best medical judgement.

Brigatinib will be administered orally at a dose of 90 mg QD for the first 7 days. Patients who have tolerated the 90 mg starting dose on Days 1 through 7 will be expected to increase their dose to 180 mg QD beginning on Day 8 and continuously every day, with a 28-day study procedure execution cycle. The study drug shall be taken approximately at the same time of the day each day. It may be taken with or without food. Patients shall be instructed to swallow the tablets whole and not crush or chew them. Patients will take the dose with water (recommended 240 mL). If a dose of brigatinib is missed or vomiting occurs after taking a dose, do not administer an additional dose and take the next dose of brigatinib at the scheduled time.

The patient's daily dose of brigatinib should not be increased to 180 mg if any of the following adverse reactions are experienced during treatment at 90 mg QD:

  • Interstitial lung disease (ILD)/pneumonitis (any grade).
  • Symptomatic bradycardia (Grade 2 or greater).
  • Grade 2 or higher visual disturbance.
  • Any other Grade 3 or higher adverse reaction.
Being tested
Brigatinib
Keywords
NSCLC, neo-adjuvant, ALK fusion, drug tolerant persister(DTP)
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

    After 7-day lead-in 90mg/day, brigatinib 180mg/day from 4 to 10weeks(optimal duration: 6 weeks)

Study groups in NCT05361564
Study groupRoleWhat they receive
BrigatinibExperimentalNot described
Receives: Drug: Brigatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. molecular candidates identified by analyzing scRNA-seq

    Molecular candidates identified by analyzing scRNA-seq from pre-treatment tumor biopsy specimens and tumor tissue acquired at the time of surgical resection.

    Measured: 10weeks (after surgery)

Secondary outcomes (10)

  1. Pathologic complete response rate (pCR)

    absence of (0%) viable tumor present histologically in the resected tumor specimen

    Measured: 10weeks (after surgery)

  2. Major pathologic response (MPR)

    ≤10% residual viable tumor following neoadjuvant therapy

    Measured: 10weeks (after surgery)

  3. Disease-free survival (DFS)

    Measured: Up to 2 years

  4. Event free survival (EFS)

    Measured: Up to 2 years

  5. Overall survival (OS)

    Measured: 6months

  6. Overall survival (OS)

    Measured: Up to 2 years

  7. Objective response rate (ORR)

    CR+PR rate based on RECIST ver 1.1 criteria.

    Measured: From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months.

  8. Rate of inability to undergo surgical resection

    Measured: 10 weeks

  9. Rate of conversion from operable to non-operative

    It will be recorded as rate of patients initially assessed as surgically resectable, who are subsequently unable to undergo surgical resection due to either treatment-related adverse events (AEs) or disease progression

    Measured: 10weeks

  10. Rate of surgical complications occurring post op period

    Measured: 16weeks (6 weeks after surgery)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2022
  2. Study startJun 2022 (estimated)
  3. Primary completionJun 2024 (estimated)
  4. Study completionJun 2024 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05361564
Sponsor's protocol ID
2022-0569-001
Status last verified
Apr 2022
First submitted
29 Apr 2022
Last updated
4 May 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

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 Yonsei University at 1 site in South Korea.

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 23 inclusion and 24 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: status not confirmed, as of the sponsor's last update on 4 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Hye Ryun Kim (+82-2-2228-8125, nobelg@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

molecular candidates identified by analyzing scRNA-seq (time frame: 10weeks (after surgery)). 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 NCT05361564.

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 4 May 2022.

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