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Biliary Tract CancerPhase 2NEOBILNCT04727541

Neoadjuvant Bintrafusp Alfa in Patients With Resectable Biliary Tract Cancer

A Phase 2 study testing Bintrafusp alfa in people with Biliary Tract Cancer and Cholangiocarcinoma, run by AIO-Studien-gGmbH at 2 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The NEOBIL study aims to investigate the feasibility, safety and efficacy of neoadjuvant Bintrafusp alfa in patients with resectable biliary tract cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Biliary Tract Cancer, Cholangiocarcinoma
What is being tested?
Bintrafusp alfa
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
2 sitesGermany
Study dates
8 Jul 2021to 5 Jan 2022
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

  • Written informed consent granted prior to initiation of any study-specific screening procedures
  • Biliary tract cancer, confirmed by histopathology, cytopathology is not sufficient
  • Resectable disease limited to the liver assessed by an interdisciplinary tumor board involving a hepatobiliary surgeon; no prior systemic therapy
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Age ≥ 18 years
  • Performance status ECOG 0-1
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  • Normal organ and bone marrow function defined as:
  • Hematopoetic: absolute neutrophil count ≥1,500/mm3, platelet count ≥ 100,000/mm3,
  • Hemoglobin ≥9 g/dL
  • Normal international normalized ratio (INR), PT ≤ 1.5 x ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN
  • Hepatic: AST ≤5 x ULN, ALT ≤ 5 x ULN, and bilirubin ≤ 3.0 x ULN.
  • Renal: Creatinine level ≤1.5 x ULN or estimated creatinine clearance ≥ 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method)
  • Special medical conditions and comorbidities:
  • Maximum Child Pugh stage A in patients with cirrhosis
  • HIV: stable on ART for at least 4 weeks, no documented evidence of multi-drug resistance, viral load of < 400 copies/mL and CD4+ T-cells ≥ 350 cells/µL.
  • HBV infection: participant on a stable dose of antiviral therapy, HBV viral load below the limit of quantification.
  • Women of childbearing potential must have a negative serum or highly sensitive urine pregnancy test performed within 7 days prior to the first dose of IMP.
  • Women of childbearing potential (WOCBP) must use HIGHLY EFFECTIVE method(s) of contraception to avoid pregnancy for the duration of study treatment and further 2 months after the last dose of IMP.
  • Male participants who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception or to abstain from sexual activity and will be instructed to adhere to either method from the time of first dose until 125 days after the last dose of investigational product. In addition, male subjects must be willing to refrain from sperm donation during this time. Azoospermic men do not require contraception.

Who cannot join

  • Metastatic disease
  • Prior surgery, systemic therapy, radiation therapy, chemoradiation, transarterial chemoembolisation (TACE), Radiofrequency ablation (RFA) or selective intraarterial Radiotherapy (SIRT) for treatment of CCA. NOTE: Laparoscopy for diagnostic procedures is allowed.
  • Drug or alcohol addiction, medical or psychological condition that may interfere with the patient´s participation in the study
  • Participation in another clinical trial with any investigational study drug (whatever the use, curative, prophylactic or diagnostic intent) within 30 days prior to enrollment
  • Pregnancy or breast feeding women
  • Regulatory and ethical criteria:
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  • Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities [§ 40 Abs. 1 S. 3 Nr. 4 AMG].
  • Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].
  • IMMUNOSUPRESSANTS: "Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)."
  • AUTOIMMUNE DISEASE: "Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible."
  • PREVIOUS MALIGNANT DISEASE: within the last 3 years except for a. superficial/non-invasive bladder cancer, or basal or squamous cell carcinoma in situ treated with curative intent; b. endoscopically resected GI cancers limited to the mucosal layer without recurrence in > 1 year.
  • INFECTIONS: "Active infection requiring systemic therapy. "
  • VACCINATION: has received or will receive a live vaccine within 30 days prior to the first administration of study intervention. Seasonal flu vaccines that do not contain a live virus are permitted. Locally approved COVID vaccines are permitted.
  • HYPERSENSITIIVTY TO BINTRAFUSP ALFA: "Known severe hypersensitivity [Grade ≥ 3 NCI CTCAE 5.0]) to investigational product bintrafusp alfa or any component in its formulations, any history of anaphylaxis, or recent, within 5 months, history of uncontrollable asthma.
  • CARDIOVASCULAR DISEASE: "Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication."
  • BLEEDING: "history of bleeding diathesis or recent major bleeding events (i.e. Grade ≥ 2 bleeding events in the month prior treatment)
  • Other severe acute or chronic medical conditions: "including drug-induced interstitial lung disease (ILD) or participant has had a history of drug-induced pneumonitis that has required oral or IV steroids", and/or other diseases, which in the opinion of the Investigator might impair the participant's tolerance for the study or ability to consistently participate in study procedures.
  • Uncontrolled diabetes as defined by HbA1c > 10.0 %.

Trial locations and contacts

2 sites in 1 country.

Germany2 sites

  • Universitätsklinikum RWTH Aachen - Klinik für Allgemein-, Viszeral- und Transplantationschirurgie

    Aachen, 52074

  • Universitätsklinikum Frankfurt - Medizinische Klinik 1

    Frankfurt, 60590

Other trials in Germany

About this study

The NEOBIL study aims to investigate the feasibility, safety and efficacy of neoadjuvant Bintrafusp alfa in patients with resectable biliary tract cancer.

Read the detailed description

The only curative therapy for biliary tract cancer (BTC) is resection. However, recurrence rates are very high with a median recurrence-free survival (RFS) time of 18 months with adjuvant chemotherapy. Bintrafusp alfa is a bifunctional fusion protein targeting TGF-β and PD-L1 that has shown promising activity in a second-line phase I BTC study. The neoadjuvant treatment approach is not a current standard in biliary tract cancer, but it is an accepted and frequently applied treatment strategy in other resectable and borderline-resectable cancers such as lung, gastric and rectal cancer. The hypothesis is that Bintrafusp alfa leads to a major pathological response in 30% of resectable BTC patients.

Being tested
Bintrafusp alfa
Medical subject headings
Biliary Tract Neoplasms, Cholangiocarcinoma

What participants receive

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

  • Bintrafusp alfaDrug

    Also called MSB0011359C, M7824

    Neoadjuvant therapy with bintrafusp alfa

Study groups in NCT04727541
Study groupRoleWhat they receive
Neoadjuvant therapy with Bintrafusp alfaExperimental1200 mg of Bintrafusp alfa will be administered by intravenous infusion every 2 weeks for a total of 2 dosages (Q2W). Subsequently, the surgery will be performed.
Receives: Drug: Bintrafusp alfa

What is being measured

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

  1. Major Pathologic Response (MPR) measured in the surgically resected tumor

    Response to neoadjuvant treatment will be determined according to the Becker score. MPR is defined by a Becker grade of 1 (1a or 1b), namely at least < 10% of viable tumor.

    Measured: 24 months

Secondary outcomes (4)

  1. Tumor Response

    Tumor Response according to RECIST1.1

    Measured: 24 months

  2. Rate of Resectability

    Rate of Resectability in biliary tract cancer patients

    Measured: 24 months

  3. Adverse events according to CTCAE V5

    Measured: 24 months

  4. Adverse Events of Special Interest

    Postoperative wound infections, impaired wound healing, wound dehiscence, prolongation of post-op hospitalization beyond 14 days.

    Measured: 24 months

Timeline

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

  1. First posted27 Jan 2021
  2. Study start8 Jul 2021
  3. Primary completion4 Oct 2021
  4. Study completion5 Jan 2022

Why it stopped: Based on results of another phase II study with bintrafusp alfa in combination with gemcitabine plus cisplatin, that was discontinued as it was unlikely to meet the primary endpoint of OS, the recruitment for this study was stopped prematurely.

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
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04727541
Sponsor's protocol ID
AIO-HEP-0120
Other IDs
2020-002605-25, MS200647_0075
Acronym
NEOBIL
Status last verified
May 2022
First submitted
25 Jan 2021
Last updated
23 May 2022
Results posted
No
Data monitoring committee
Yes
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 Bintrafusp alfa in people with Biliary Tract Cancer and Cholangiocarcinoma, run by AIO-Studien-gGmbH at 2 sites in Germany.

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 18 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 23 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 2 sites in Germany. 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 stopped early (reason given: Based on results of another phase II study with bintrafusp alfa in combination with gemcitabine plus cisplatin, that was discontinued as it was unlikely to meet the primary endpoint of OS, the recruitment for this study was stopped prematurely.). Results are not available in the source record.

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?

Major Pathologic Response (MPR) measured in the surgically resected tumor (time frame: 24 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 NCT04727541.

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 23 May 2022.

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