Treatment for high-risk resectable cholangiocarcinoma using combination therapy

Perioperative Treatment of High-risk Resectable Cholangiocarcinoma with Hepatic Arterial Infusion Chemotherapy (HAIC) Combined with Atezo/bevacizumab: a Multicenter Phase II Study (NeoBrave CCA)

This study is testing a combination of three chemotherapy drugs before surgery to see if it can help people with high-risk bile duct cancer have better surgery results and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Peking University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, bevacizumab, Durvalumab, atezolizumab
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT06739252 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of perioperative treatment combining Gemcitabine, Oxaliplatin, and 5FU for patients with high-risk resectable intrahepatic and perihilar cholangiocarcinoma. The study aims to enhance surgical outcomes and prolong survival rates by administering neoadjuvant therapy before surgery. It targets patients who exhibit specific high-risk recurrence factors and have been confirmed for surgical resection. The trial is designed to address the lack of large-scale studies confirming the benefits of neoadjuvant therapies in biliary tract cancers.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-80 with confirmed intrahepatic or perihilar cholangiocarcinoma who meet specific high-risk criteria for recurrence.

Not a fit: Patients with advanced metastatic disease or those not meeting the surgical resection criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve surgical outcomes and survival rates for patients with high-risk cholangiocarcinoma.

How similar studies have performed: While there have been exploratory studies on neoadjuvant treatment for biliary tract cancers, this approach is still under investigation and lacks large-scale phase III trials confirming its efficacy.

Eligibility criteria

Inclusion Criteria:

1. Age: 18-80 years, regardless of gender; 2. Diagnosis of intrahepatic cholangiocarcinoma or perihilar cholangiocarcinoma confirmed by pathological tissue/cytological diagnosis; 3. Meeting the criteria for surgical resection; 4. Presence of high-risk recurrence factors: iCCA (single mass \>5cm, or multiple lesions, or accompanied by satellite lesions, or accompanied by portal vein/hepatic vein invasion, or CA199 \>200U/ml); pCCA (invasion of secondary branches of the bile duct, or invasion of portal vein/hepatic artery, or accompanied by intrahepatic metastasis); 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1; 6. Child-Pugh class A; 7. Normal major organ function, meeting the following standards:

1. Blood routine examination:

   A. Hb≥90 g/L; B. ANC≥1.5×10\^9/L; C. PLT≥75×10\^9/L;
2. Biochemical examination:

A. ALB ≥30g/L; B. ALT and AST\<5×ULN; C. TBiL ≤2×ULN; D. Creatinine ≤1.5×ULN; (3) Coagulation function: A. International normalized ratio (INR) ≤1.5×ULN; B. Activated partial thromboplastin time (APTT) ≤1.5×ULN. 8. Subjects voluntarily join this study, sign informed consent, have good compliance, and cooperate with follow-up.

Exclusion Criteria:

1. Regional multiple lymph node metastases or fusion, retroperitoneal lymph node metastases;
2. Peritoneal metastasis, distant metastasis;
3. Previous systemic treatment, including but not limited to chemotherapy, targeted therapy, immunotherapy;
4. Previous local treatment, including but not limited to HAIC, TACE, TARE, ablation, radiotherapy, etc.;
5. Severe hepatic artery variation;
6. Allergy to contrast agents;
7. Allergy to oxaliplatin;
8. Vaccination with live attenuated vaccine within 4 weeks prior to first administration or planned during the study period;
9. Presence of \> grade 1 peripheral neuropathy;
10. Presence of any active autoimmune disease or history of autoimmune disease;
11. Complication of other malignancies (except for basal cell or squamous cell skin cancer or cervical carcinoma in situ that was treated curatively);
12. Human immunodeficiency virus (HIV) infection or known acquired immune deficiency syndrome (AIDS);
13. Within 6 months prior to entering the study, occurrences of the following: myocardial infarction, severe/unstable angina, NYHA class II heart failure or above, poorly controlled arrhythmias (including QTcF interval male \>450 ms, female \>470 ms, QTcF interval calculated using the Fridericia formula), symptomatic congestive heart failure;
14. Hypertension that cannot be well controlled with antihypertensive medications (systolic blood pressure ≥140 mmHg or diastolic pressure ≥90 mmHg);
15. Abnormal coagulation function (INR\>1.5 or APTT\>1.5×ULN), with bleeding tendency or currently undergoing thrombolytic therapy, anticoagulant therapy, or antiplatelet therapy;
16. Known hereditary or acquired bleeding and thrombosis tendencies, such as hemophilia, coagulation function disorders, thrombocytopenia, splenomegaly, etc.;
17. Significant hemoptysis occurring within 2 months before entering the study, or daily sputum blood volume reaching half a teaspoon (2.5 ml) or more;
18. Patients at risk of gastrointestinal bleeding, including:

(1) Presence of active peptic ulcer lesions; (2) History of melena or hematemesis within the past 3 months; (3) For stool occult blood (+) or (+/-), need to retest stool routine within 1 week; if still (+) or (+/-), esophagogastroduodenoscopy is needed; if ulcers or bleeding diseases are present and considered to have potential bleeding risks by the treating physician; 19. Thrombotic events occurring within 6 months prior to entering the study, such as cerebrovascular accidents (including transient ischemic attacks, intracerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; 20. Infections requiring drug intervention occurring within 4 weeks prior to first medication (such as requiring intravenous antibiotics, antifungal or antiviral medications), or fever of unknown origin \>38.5°C during screening/ prior to first medication; 21. Participation in any other drug clinical trials within 4 weeks prior to first administration; 22. Known history of substance abuse or drug addiction; 23. Presence of other serious physical or mental diseases or abnormal laboratory tests that may increase the risk of participation in the study or interfere with study results, and patients deemed unsuitable for participation in this study by the investigator.

Where this trial is running

Beijing, Beijing

• Peing University Cancer Hospital — Beijing, Beijing, China (Recruiting)

Study contacts

• Study coordinator: Xiaodong Wang, M.D.

Conditions Intrahepatic Cholangiocarcinoma; Perihilar Cholangiocarcinoma