NCT04727541终止2 期
Neoadjuvant Bintrafusp Alfa in Patients With Resectable Biliary Tract Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Major Pathologic Response (MPR) measured in the surgically resected tumor
研究概览
简要总结
The NEOBIL study aims to investigate the feasibility, safety and efficacy of neoadjuvant Bintrafusp alfa in patients with resectable biliary tract cancer.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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:
- •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 %.
研究组 & 干预措施
Neoadjuvant therapy with Bintrafusp alfa
Experimental
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.
干预措施: Bintrafusp alfa (Drug)
结局指标
主要结局
Major Pathologic Response (MPR) measured in the surgically resected tumor
时间窗: 24 months
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.
次要结局
- Tumor Response(24 months)
- Rate of Resectability(24 months)
- Adverse events according to CTCAE V5(24 months)
- Adverse Events of Special Interest(24 months)
研究者
研究点 (2)
Loading locations...
相似试验
终止
2 期
Bintrafusp Alfa Before Surgery for the Treatment of Untreated Resectable Non-small Cell Lung CancerResectable Lung Non-Small Cell CarcinomaStage I Lung Cancer AJCC v8Stage IA1 Lung Cancer AJCC v8Stage IA2 Lung Cancer AJCC v8Stage IA3 Lung Cancer AJCC v8Stage IB Lung Cancer AJCC v8Stage II Lung Cancer AJCC v8Stage IIA Lung Cancer AJCC v8Stage IIB Lung Cancer AJCC v8Stage IIIA Lung Cancer AJCC v8Stage IIIB Lung Cancer AJCC v8NCT04560686M.D. Anderson Cancer Center2
进行中（未招募）
1 期
eoadjuvant Bintrafusp alfa in patients with resectable biliary tract cancer (NEOBIL)Treatment-naive subjects with a diagnosis of resectable biliary tract cancer, confirmed by histopathologyMedDRA version: 20.0Level: PTClassification code 10004593Term: Bile duct cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10004597Term: Bile duct cancer resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10004598Term: Bile duct carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10007289Term: Carcinoma bile ductSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.0Level: LLTClassification code 10004601Term: Bile duct carcinoma resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)EUCTR2020-002605-25-DEAIO-Studien-gGmbH24
进行中（未招募）
2 期
Neoadjuvant Immune Checkpoint Blockade in Resectable Malignant Pleural MesotheliomaMesotheliomaNCT03918252Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins30
Unknown
2 期
Neoadjuvant FOLFIRINOX or Nab-paclitaxel With Gemcitabine for Borderline Resectable Pancreatic CancerBorderline Resectable Pancreatic CancerNCT02717091Nagoya University50
尚未招募
2 期
Neoadjuvant Therapy of Targeted Immunotherapy Combined With Chemotherapy for Locally Advanced HNSCCHead and Neck Squamous Cell CarcinomaNeoadjuvant TherapyPD-L1AnlotinibNCT06699498The First Affiliated Hospital with Nanjing Medical University45