Treatment-naive subjects with a diagnosis of resectable biliary tract cancer, confirmed by histopathology MedDRA version: 20.0 Level: PT Classification code 10004593 Term: Bile duct cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10004597 Term: Bile duct cancer resectable System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version:
Conditions
Interventions
Product Name: Bintrafusp Alfa
Product Code: MSB0011359C
Pharmaceutical Form: Infusion
INN or Proposed INN: BINTRAFUSP ALFA
Other descriptive name: M7824)
Concentration unit: mg/ml milligram(s)/millili
Sponsors
AIO-Studien-gGmbH
Eligibility
Sex/Gender
All
Inclusion 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 xaminations 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 =65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
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/noninvasive 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. 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 ( 10.0 %.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: after approx. 24 months;Secondary Objective: include exploratory objectives namely accumulation of further feasibility data (i.e. safety data, additional efficacy data) as well as a translational research part investigating changes in a subjects’ immune activation determined by blood tests and tissue analysis before and after treatment with Bintrafusp alfa;Main Objective: To explore the efficacy of preoperative Bintrafusp alfa (M7824, MSB0011359C) in inducing a major pathological response in biliary tract cancer patients.;Primary end point(s): Major Pathologic Response measured in the surgically resected tumor | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Tumor response according to RECIST1.1 - Rate of resectability - Adverse events according to CTCAE V5 - Adverse events of special interest (postoperative wound infections, impaired wound healing, wound dehiscence, prolongation of post-op hospitalization beyond 14 days);Timepoint(s) of evaluation of this end point: after approx. 24 months | — |
Countries
Germany
Contacts
Public ContactAIO-Studien-gGmbH
AIO-Studien-gGmbH
Outcome results
None listed