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Esophageal Squamous Cell Carcinoma (ESCC)Phase 2BEARNCT04839471

BI-754091 and Afatinib for Refractory Esophageal Squamous Cell Carcinoma (BEAR Study)

A Phase 2 study testing BI-754091 plus afatinib in people with Esophageal Squamous Cell Carcinoma (ESCC), run by National Health Research Institutes, Taiwan at 4 sites in Taiwan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open-label, single arm, multi-center study, assessing efficacy and safety of BI-754091 in combination with afatinib as treatment in patients with advanced or metastatic ESCC refractory to at least 1 line of systemic treatment (including chemotherapy or radiation therapy). Read more about this study

Who is it for?
Ages 20 years and older
What is being tested?
BI-754091 plus afatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
4 sitesTaiwan
Study dates
6 Aug 2021to 19 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

  • histologically confirmed esophagus squamous cell carcinoma (ESCC);
  • metastatic or unresectable disease;
  • previously treated with at least 1 line of platinum based chemotherapy regimens (including cisplatin or carboplatin);
  • Less than 6 months after the most recent treatment, with documented disease progression by imaging studies according to RECIST 1.1 criteria;
  • presence of at least one measurable lesion according to RECIST 1.1. (the measurable lesion cannot be the biopsy lesion)
  • adequate hematopoietic function which is defined as below:
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  • hemoglobin level ≥ 9 g/dL;
  • absolute neutrophil count (ANC) ≥ 1,500/mm3;
  • platelet count ≥ 100,000/mm3;
  • adequate hepatic function which is defined as below:
  • total bilirubin < 2 mg/dL;
  • Alanine aminotransferase (ALT) ≤ 3 x ULN;
  • adequate renal function: creatinine clearance rate (CCr) ≥ 50 mL/min ((based upon 24-hour urine collection or calculated by Cockroft-Gault formula); < Cockroft-Gault formula > Male: ((140 - age) × weight [kg])/(72 × serum creatinine[mg/dL]) Female: 0.85 x estimate for male
  • age of 20 years or above;
  • ECOG performance status 0-1;
  • life expectancy of at least 12 weeks;
  • ability to take oral medication;
  • ability to understand and willingness to sign a written informed consent document.
  • Subjects with chronic hepatitis B virus infection (HBV surface antigen (HBsAg) positive) must start antiviral therapy with nucleoside analogs (e.g., entecavir or tenofovir, according to current practice guidelines) before start of study drug treatment and maintained throughout the experimental therapy.

Who cannot join

  • Any investigational treatment, anti-tumour treatment within 4 weeks or within 5 half-life periods (whichever is shorter) prior to the initiation of trial treatment.
  • Major surgery ('major' according to the Investigator's assessment) performed within 12 weeks prior to first trial treatment or planned within 12 weeks after screening, e.g., hip replacement.
  • Any of the following cardiac criteria:
  • Mean resting corrected QT interval (QTc) >470 msec.
  • Any clinically important abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle branch block, third degree heart block.
  • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years-of-age, or any concomitant medication known to prolong the QT interval.
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  • Patients with an ejection fraction (EF) <55% or the lower limit of normal of the institutional standard (if the lower limit of normal of institutional standard is higher than 55%) will be excluded. Only in cases where the Investigator (or the treating physician or both) suspects cardiac disease with negative effect on the EF will the EF be measured during screening using an appropriate method according to local standards to confirm eligibility (e.g., echocardiogram, multi-gated acquisition scan). An historic measurement of EF no older than 6 months prior to first administration of trial drug can be accepted provided that there is clinical evidence that the EF value has not worsened since this measurement in the opinion of the Investigator or of the treating physician or both.
  • Known history of human immunodeficiency virus infection.
  • Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy.
  • Known history of severe hypersensitivity reactions to other mAbs or known hypersensitivity to the trial drugs or their excipients.
  • Known presence of symptomatic central nervous system (CNS) metastases, unless asymptomatic and off corticosteroids and anti-convulsant therapy for at least 2 weeks prior start of treatment.
  • Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of study treatment.
  • Men who plan to father a child while in the trial and for at least 6 months after the last administration of trial medication.
  • Other malignancy within the past 5 years except for adequately treated basal or squamous cell skin cancer or cervical cancer in situ.
  • Previously treated with any PD-1 inhibitors, PD-L1 inhibitors, or CTLA-4 inhibitors.
  • Previously treated with gefitinib, erlotinib, afatinib, osimertinib.
  • History or known presence of interstitial pneumonia.
  • Presence of grade 2 or above ascites or pleural effusion.
  • Presence of grade 2 or above diarrhea.
  • Presence of mental disease or psychotic manifestation.
  • Active or uncontrolled infection.
  • significant medical conditions that is contraindicated to study medication or render patient at high risk from treatment complications based on investigator's discretion;
  • pregnant women or nursing mothers, or positive pregnancy test for women of childbearing potential. Patients with childbearing potential shall have effective contraception for both the patient and his or her partner during the study.
  • Received a live vaccine within 30 days prior to the first dose of trial treatment. Seasonal flu vaccines that do not contain live virus are permitted.
  • Patients with tracheo-esophageal fistula or broncho-esophagal fistula.

Trial locations and contacts

4 sites in 1 country.

Taiwan4 sites

  • Kaohsiung Medical University Chung-Ho Memorial Hospital

    Kaohsiung City

  • China Medical University Hospital

    Taichung

  • National Cheng-Kung University Hospital

    Tainan

  • Taipei Veterans General Hospital

    Taipei

Other trials in Taiwan

About this study

Official title: BI-754091 and Afatinib for Refractory Esophageal Squamous Cell Carcinoma (BEAR Study): a Single-arm, Phase II Study

This is an open-label, single arm, multi-center study, assessing efficacy and safety of BI-754091 in combination with afatinib as treatment in patients with advanced or metastatic ESCC refractory to at least 1 line of systemic treatment (including chemotherapy or radiation therapy).

Read the detailed description

Esophageal cancer (EsC) is the sixth leading cancer in the world and is a complex disease with heterogenous subgroups. The squamous cell carcinoma subgroup usually involves the upper part of esophagus and typically occurs in mid-age males. Standard treatment for esophageal squamous cell carcinoma (ESCC) utilizes a trimodality approach comprising of surgery (including resection and reconstruction and/or feeding tube support), radiotherapy and chemotherapy. Addition of tyrosine kinase inhibitors has not shown a benefit in advanced or metastatic ESCC. Immunotherapy, especially checkpoint inhibitors that target the PD-1/PD-L1 axis, have demonstrated clinical benefit in phase III trials for head neck squamous cell carcinoma (HNSCC). This led to the anticipation that immunotherapy could also be useful ESCC due to similar histologic cell types, but before the results presented from KEYNOTE-181, no phase III trial have proven such benefit. It must be emphasized that KEYNOTE-180, KEYNOTE-181 and ONO-4538-07 demonstrated efficacy of immune checkpoint inhibitors in ESCC patients were only 14.3-17%; furthermore, USFDA approved pembrolizumab monotherapy for second line treatment in advanced esophageal cancer only with CPS score≧10. Thus, the benefit of immunotherapy in patients with CPS score less than 10 remains uncertain. With effective target therapy and immunotherapy options lacking, there is a huge unmet need for chemotherapy resistant, advanced or metastatic ESCC. In light of a recent retrospective cohort study demonstrating clinical benefit of using pembrolizumab combined with afatinib for refractory HNSCC, the investigators decide to implement the similar regimen (afatinib plus BI704591) in ESCC patients who had failed multiple lines of chemotherapy

Being tested
BI-754091 plus afatinib
Keywords
immunotherapy, target therapy
Medical subject headings
Esophageal Squamous Cell Carcinoma

What participants receive

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

  • BI-754091 plus afatinibDrug

    Eligible patients will receive BI-754091 240 mg on D1, afatinib 30 mg/day on day 1 to 21 in a 3-week cycle.

Study groups in NCT04839471
Study groupRoleWhat they receive
BI-754091 plus afatinibExperimentalBI-754091 plus afatinib
Receives: Drug: BI-754091 plus afatinib

What is being measured

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

  1. ORR (RECIST 1.1)

    to evaluate disease objective response rate (ORR) by RECIST 1.1

    Measured: 2 years

Secondary outcomes (6)

  1. DoR

    to evaluate duration of response

    Measured: 2 years

  2. OS

    to evaluate overall survival

    Measured: 2 years

  3. PFS

    to evaluate progression-free survival

    Measured: 2 years

  4. ORR (iRECIST)

    to evaluate disease objective response rate by iRECIST

    Measured: 2 years

  5. DCR

    to evaluate disease control rate

    Measured: 2 years

  6. To explore the treatment-related adverse events as assessed by CTCAE v5.0

    Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Measured: 2 years

Timeline

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

  1. First posted9 Apr 2021
  2. Study start6 Aug 2021
  3. Primary completion24 Jul 2023
  4. Study completion19 Jun 2024

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
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04839471
Sponsor's protocol ID
T1220
Other IDs
1200-0320
Acronym
BEAR
Status last verified
Jun 2024
First submitted
31 Mar 2021
Last updated
8 Jul 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Kao HF, Liao BC, Huang YL, Huang HC, Chen CN, Chen TC, Hong YJ, Chan CY, Chia JS, Hong RL. Afatinib and Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (ALPHA Study): A Phase II Study with Biomarker Analysis. Clin Cancer Res. 2022 Apr 14;28(8):1560-1571. doi: 10.1158/1078-0432.CCR-21-3025.

    PubMed 35046059

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BI-754091 plus afatinib in people with Esophageal Squamous Cell Carcinoma (ESCC), run by National Health Research Institutes, Taiwan at 4 sites in Taiwan.

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 19 inclusion and 25 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: finished, as of the sponsor's last update on 8 Jul 2024. 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 Taiwan. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

ORR (RECIST 1.1) (time frame: 2 years). 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 NCT04839471, 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 8 Jul 2024.

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