Neoadjuvant Bintrafusp Alfa in Patients With Resectable Biliary Tract Cancer

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Brief Title

Neoadjuvant Bintrafusp Alfa in Patients With Resectable Biliary Tract Cancer

Official Title

Neoadjuvant Bintrafusp Alfa in Patients With Resectable Biliary Tract Cancer

Brief Summary

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

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

 Tumor Response

Condition

Biliary Tract Cancer

Intervention

Bintrafusp alfa

Study Arms / Comparison Groups

 Neoadjuvant therapy with Bintrafusp alfa
Description:  1200 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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

24

Start Date

July 8, 2021

Completion Date

September 2023

Primary Completion Date

February 2023

Eligibility Criteria

        Inclusion Criteria:

          1. Written informed consent granted prior to initiation of any study-specific screening
             procedures

          2. Biliary tract cancer, confirmed by histopathology, cytopathology is not sufficient

          3. Resectable disease limited to the liver assessed by an interdisciplinary tumor board
             involving a hepatobiliary surgeon; no prior systemic therapy

          4. 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.

          5. Age ≥ 18 years

          6. Performance status ECOG 0-1

          7. 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)

          8. 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.

          9. 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.

         10. 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.

         11. 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.

        Exclusion Criteria:

          1. Metastatic disease

          2. 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.

          3. Drug or alcohol addiction, medical or psychological condition that may interfere with
             the patient´s participation in the study

          4. Participation in another clinical trial with any investigational study drug (whatever
             the use, curative, prophylactic or diagnostic intent) within 30 days prior to
             enrollment

          5. Pregnancy or breast feeding women

          6. Regulatory and ethical criteria:

               -  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].

          7. 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)."

          8. 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."

          9. 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.

         10. INFECTIONS: "Active infection requiring systemic therapy. "

         11. 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.

         12. 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.

         13. 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."

         14. BLEEDING: "history of bleeding diathesis or recent major bleeding events (i.e. Grade ≥
             2 bleeding events in the month prior treatment)

         15. 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.

         16. Uncontrolled diabetes as defined by HbA1c > 10.0 %.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Oliver Waidmann, Prof.Dr., +49 (0) 30 8145 344, [email protected]

Location Countries

Germany

Location Countries

Germany

Administrative Informations


NCT ID

NCT04727541

Organization ID

AIO-HEP-0120

Secondary IDs

2020-002605-25

Responsible Party

Sponsor

Study Sponsor

AIO-Studien-gGmbH

Collaborators

 Merck Serono GmbH, Germany

Study Sponsor

Oliver Waidmann, Prof.Dr., Principal Investigator, Universitätsklinikum Frankfurt


Verification Date

September 2021