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Advanced Malignant NeoplasmPhase 2NCT03868423

Brigatinib in Treating Patients With ALK and ROS1 Gene Alterations and Locally Advanced or Metastatic Solid Cancers

A Phase 2 study testing Brigatinib, Laboratory Biomarker Analysis and Quality-of-Life Assessment in people with Advanced Malignant Neoplasm and ALK Fusion Protein Expression, run by Sameek Roychowdhury at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase II trial studies how well brigatinib works in treating patients with ALK and ROS1 gene alterations and solid cancers that have spread to nearby tissue and lymph nodes or other places in the body. Brigatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Brigatinib, Laboratory Biomarker Analysis and Quality-of-Life Assessment
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
20 Mar 2019to 30 Dec 2021
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumors
  • Patients must have activating genomic alterations in ALK or ROS1 (mutations, fusions or amplifications) by any validated Clinical Laboratory Improvement Act (CLIA)-certified molecular testing (fluorescence in situ hybridization [FISH], polymerase chain reaction [PCR] or next-generation sequencing [NGS] data are acceptable); CLIA validated results from other institutions and commercial diagnostic labs (e.g. Foundation Medicine) are also acceptable
  • Patients with progressive disease on any previous therapy including crizotinib and other ALK tyrosine kinase inhibitors (TKIs), chemotherapy or immunotherapy
  • Patients with locally advanced or metastatic solid tumors who have received no previous therapy of any kind (i.e. first-line therapy) are eligible
  • Patients with brain metastases or metastases elsewhere within the central nervous system (CNS) are eligible for study; patients must be neurologically stable and asymptomatic
  • Patients with tumor suitable for biopsy (as assessed by trained specialists in interventional radiology) and medically fit to undergo a biopsy or surgical procedure will have mandatory pre-treatment tumor biopsy or sampling; however, if patients do not have a tumor suitable for biopsy but have another tissue (preferably progressive metastatic site) available for molecular evaluation this will be acceptable
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  • Patients with solid tumors must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1; Note: previously irradiated lesions may not be used for target lesions; unless there is unambiguous radiological progression after radiotherapy; brain lesions may not be used as target lesions if they were: 1) previously treated with whole brain radiation therapy (WBRT) within 3 months, or 2) previously treated by stereotactic radiosurgery (SRS) or surgical resection
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Life expectancy of greater than 3 months
  • Patients with multiple malignancies remain eligible
  • Patients with an inherited cancer syndrome or a medical/family history suggestive of an inherited cancer syndrome remain eligible
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and through 4 months after the end of treatment; for women of childbearing potential, a negative pregnancy test must be documented prior to registration
  • Absolute neutrophil count >= 1,500/mcL
  • Hemoglobin >= 10 g/dL
  • Platelet count >= 75,000/mcL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN), unless due to Gilbert?s syndrome (< 5 if metastatic involvement of the liver)
  • Serum lipase =< 1.5 x ULN
  • Serum amylase =< 1.5 x ULN
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
  • Left ventricular ejection fraction (LVEF) >= 50% by echocardiogram or multi-gated acquisition (MUGA)
  • Normal QT interval on screening electrocardiogram (ECG), defined as QT interval corrected of =< 450 ms in males or =< 470 ms in females
  • Serum creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockroft-Gault formula) >= 60 mL/min OR 24-hour urine creatinine clearance >= 60 mL/min
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • Patients with hematological malignancies
  • Patients with ALK positive (+) lung cancer
  • Major surgery (e.g. thoracic, abdominal, vascular, neurosurgery) within 30 days prior to registration on study
  • Pregnant women or mothers who are breastfeeding
  • Patients who are incarcerated
  • Patients who have a history or the presence at baseline of pulmonary interstitial disease or drug-related pneumonitis, or radiation pneumonitis
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  • Patients who have a known history of human immunodeficiency virus (HIV); testing not required in the absence of history
  • Patients with history of clinically significant bleeding disorder or history of active significant gastrointestinal (GI) bleeding within 3 months of first dose of brigatinib
  • Patients who have malabsorption syndrome or other GI illness or condition that could affect oral absorption of the study drug
  • History of allergic or suspected hypersensitivity reactions attributed to compounds of similar chemical or biologic composition to brigatinib
  • Patients with history of clinically significant atrial arrhythmias (requiring any anti-arrhythmic therapy or as determined by the treating physician) or any history of ventricular arrhythmias
  • Patients who have significant, uncontrolled or active cardiovascular disease, including but not restricted to the following:
  • Myocardial infarction (MI) within 6 months prior to first dose of brigatinib
  • Unstable angina (UA) within 6 months prior to first use
  • Decompensated congestive heart failure within 6 months prior to first dose
  • Cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to first dose
  • Clinically significant, uncontrolled intercurrent illness including, but not limited to:
  • Symptomatic or active infection requiring intravenous (IV) antibiotics
  • Psychiatric illness and/or social situations that would limit compliance with completion of study requirements
  • Patients on medications known to be associated with torsades de pointes
  • Patients who have uncontrolled hypertension; patients with hypertension should be under treatment on study entry to control blood pressure
  • Patients who have received cytotoxic chemotherapy, investigational agents, or radiation within 14 days, except stereotactic radiosurgery (SRS) or stereotactic body radiosurgery
  • Patients who have received monoclonal antibodies or had major surgery within 30 days of the first dose of brigatinib
  • Patients who have not recovered (=< Common Terminology Criteria for Adverse Events [CTCAE] grade 1) from adverse events (with the exception of alopecia) due to agents administered more than 4 weeks earlier
  • Patients with symptomatic CNS metastases that are neurologically unstable or require increasing dose of corticosteroids
  • Patients with current spinal cord compression

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: Phase II Study of Brigatinib for Advanced Solid Cancers Harboring Genomic Alterations in ALK (Excluding Lung) and ROS1 Oncogenes

This phase II trial studies how well brigatinib works in treating patients with ALK and ROS1 gene alterations and solid cancers that have spread to nearby tissue and lymph nodes or other places in the body. Brigatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the overall response rate (ORR) of brigatinib in patients with advanced solid tumors harboring genomic alterations in ALK (excluding lung) and ROS1 (all solid tumors).

SECONDARY OBJECTIVES:

  1. To assess the safety and tolerability of brigatinib in patients with advanced solid tumors harboring genomic alterations in ALK (excluding lung) and ROS1 (all solid tumors).

II. To assess progression free survival (PFS) and overall survival (OS) in patients with advanced ALK or ROS1 mutated solid tumors treated with brigatinib.

III. To assess sensitivity and durability of response to brigatinib in different solid tumor types.

IV. To assess the role of intertumoral and intratumoral heterogeneity in the development of resistance to brigatinib.

  1. To identify candidate genomic (including circulating tumor deoxyribonucleic acid [DNA]) and proteomic biomarkers of tumor sensitivity and resistance to brigatinib using high-throughput approaches (exome, transcriptome, reverse phase protein array [RPPA]).

TERTIARY OBJECTIVES:

  1. Correlation of brigatinib exposure with efficacy and safety. II. Correlation of tumor and plasma biomarkers with brigatinib efficacy and safety.

OUTLINE:

Patients receive brigatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 52 weeks.

Being tested
Brigatinib, Laboratory Biomarker Analysis, Quality-of-Life Assessment, Questionnaire Administration
Medical subject headings
Brain Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BrigatinibDrug

    Also called Alunbrig, AP 26113, AP-26113, AP26113

    90 mg orally QD for 7 days followed by 180 mg orally QD continuously thereafter. One cycle of therapy will consist of 28 days of treatment.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT03868423
Study groupRoleWhat they receive
Treatment (brigatinib)ExperimentalPatients receive brigatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Brigatinib; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

What is being measured

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

  1. Overall response rate assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

    Response for tumors will be assessed using the RECIST 1.1 criteria (using computed tomography scans or calipers by clinical exam) where response will be defined as a partial or complete response. Will be calculated with 95% binomial confidence intervals for the estimate of the proportion of responses.

    Measured: Up to 52 weeks

Secondary outcomes (11)

  1. Confirmed objective response rate (ORR)

    Will be assessed by central independent review committee per RECIST version 1.1.

    Measured: Up to 52 weeks

  2. Time to response

    Will be evaluated.

    Measured: Up to 52 weeks

  3. Duration of response

    Will be evaluated.

    Measured: From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 52 weeks

  4. Time on treatment

    Will be evaluated.

    Measured: Up to 52 weeks

  5. Disease control rate

    Will be assessed by RECIST version 1.1.

    Measured: Up to 52 weeks

  6. Incidence of adverse events assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

    Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

    Measured: Up to 52 weeks

  7. Overall survival

    Kaplan-Meier curves will be used to estimate the survival distributions of overall survival.

    Measured: From treatment initiation to death due to any cause, assessed up to 52 weeks

  8. Progression-free survival

    Kaplan-Meier curves will be used to estimate the survival distributions of progression-free survival.

    Measured: From the date of study registration to the date of event (ie, death and/or disease progression) or the date of last follow-up if no event has occurred, up to 52 weeks

  9. Clinical benefit rate

    Will be calculated by the number of patients who have achieve a response and/or are progression-free and alive at 6 months divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for clinical benefit rate will be calculated.

    Measured: 6 months

  10. Rate of participation of those screened and identified with the eligible genetic alterations

    The logistical aspects of the trial will be evaluated and summarized. Disease group-specific outcomes will also be summarized and described, although we will not be powered for any formal evaluation within a disease or histology subset.

    Measured: Up to 52 weeks

  11. Rate of enrollment of those screened and identified with the eligible genetic alterations

    The logistical aspects of the trial will be evaluated and summarized. Disease group-specific outcomes will also be summarized and described, although we will not be powered for any formal evaluation within a disease or histology subset. Genes will be evaluated in aggregate from whole exome and transcriptome sequencing.

    Measured: Up to 52 weeks

Timeline

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

  1. First posted11 Mar 2019
  2. Study start20 Mar 2019
  3. Primary completion20 Nov 2020
  4. Study completion30 Dec 2021 (estimated)

Why it stopped: PI decision

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03868423
Sponsor's protocol ID
OSU-17060
Other IDs
NCI-2017-01394, P30CA016058
Status last verified
Feb 2022
First submitted
4 Feb 2019
Last updated
18 Feb 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Brigatinib, Laboratory Biomarker Analysis and Quality-of-Life Assessment in people with Advanced Malignant Neoplasm and ALK Fusion Protein Expression, run by Sameek Roychowdhury at 1 site 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 23 inclusion and 26 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: withdrawn, as of the sponsor's last update on 18 Feb 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 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Overall response rate assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (time frame: Up to 52 weeks). 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 NCT03868423.

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 18 Feb 2022.

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