Perioperative Treatment of High-risk Resectable CCA With HAIC Plus A+T: Neobrave CCA

NCT06739252 | Terminated Phase 2

• 1 other identifier: Neobrave-CCA
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Among resectable biliary tract cancers (BTC) patients, surgery has historically been the standard treatment, but even with curative surgery, the cure rates remain relatively low, with most patients relapsing in the short term and a 5-year survival rate of approximately 50% or lower. In BTC, numerous exploratory studies on neoadjuvant treatment have been conducted, yielding varying results, but overall indicating that neoadjuvant therapy can enhance R0 resection rates and prolong survival in certain patients, particularly those with borderline resectable and locally advanced BTC. Currently, there remains a lack of large prospective randomized controlled phase III clinical trials confirming the exact benefits of neoadjuvant and adjuvant therapies for BTC. The SWOG 1815 study is a randomized, open-label phase III trial comparing GAP with Gemcitabine/Cisplatin (GC) in patients with advanced BTC. In exploratory subgroup analyses, GAP improved mOS compared to GC in patients with locally advanced disease (19.2 vs. 13.7 months; HR 0.67, 95% CI 0.42-1.06, p = 0.09). Thus, patients with locally advanced disease may benefit more from GAP treatment. In another multi-institutional, single-arm, phase II trial, patients received a total of 4 cycles of preoperative GAP (Gemcitabine 800 mg/m2, Cisplatin 25 mg/m2, nab-Paclitaxel 100 mg/m2, administered on days 1 and 8 of a 21-day cycle) before attempting radical surgical resection. The median follow-up time for all patients was 17 months; the disease control rate was 90%. Therefore, the preoperative neoadjuvant therapy of Gemcitabine, Cisplatin, and nab-Paclitaxel for iCCA is feasible and safe, with no adverse effects on perioperative outcomes. More recently, neoadjuvant D + GemCis was confirmed to result in a higher surgical resection rate among patients with locally advanced BTC, and surgical resection was associated with higher survival rates. The investigators previously explored a prospective phase II study and showed promising results of HAIC using oxaliplatin and 5-fluorouracil for perihilar cholangiocarcinoma (pCCA), with an objective response rate (ORR) of 67.6%, a mPFS of 12.2 months, and a mOS of 20.5 months. Another phase II prospective study enrolled 32 untreated BTC patients and used HAIC combined with anti-PD-1 monoclonal antibody and bevacizumab as a first-line treatment regimen, the ORR was 84.3%, and the disease control rate (DCR) was 96.9%, with one-year PFS and OS rates of 53.8% and 80.4%, respectively.

Conditions

Intrahepatic Cholangiocarcinoma (Icc); Perihilar Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• MPR

  the proportion of residual active tumor cells ≤50%

  From the date of treatment beginning to the date of pathological results after the surgery, assessed up to 6 months since the date of treatment beginning

Secondary Outcomes (8)

• pCR

  From the date of treatment beginning to the date of pathological results after the surgery, assessed up to 6 months since the date of treatment beginning

• ORR

  Evaluation of tumor burden based on RECIST 1.1 criteria through study completion, an average of once per 3 months.

• DCR

  Evaluation of tumor burden based on RECIST 1.1 criteria through study completion, an average of once per 3 months.

• R0 resection rate

  From the date of treatment beginning to the date of pathological results after the surgery, assessed up to 6 months since the date of treatment beginning

• RFS

  From date of treatment beginning until the date of first documented recurrence, assessed up to 100 months

Study Arms (1)

Neobrave

EXPERIMENTAL

Perioperative treatment

Combination Product: Gemcitabine Oxaliplatin and 5FU

Interventions

Gemcitabine Oxaliplatin and 5FU COMBINATION_PRODUCT

The perioperative treatment plan includes neoadjuvant therapy and adjuvant therapy. Neoadjuvant therapy consists of three cycles of HAIC combined with atezolizumab and bevacizumab (atezo/bev), while adjuvant therapy includes two cycles of HAIC combined with atezolizumab and bevacizumab (atezo/bev), along with additional capecitabine or tegafur as auxiliary maintenance treatment for three cycles. The total treatment duration for the perioperative period is six months. HAIC regimen: gemcitabine (1,000 mg/m2, 2h, d1) + oxaliplatin (35 mg/m2, 2h, d1-2) + 5-FU (0.75g/m2, 22h, d1-2); atezolizumab (PD-L1 inhibitor): 1200 mg, intravenous infusion, administered within 24 hours before HAIC treatment; bevacizumab: 7.5 mg/kg, intravenously infused before HAIC treatment (bevacizumab use is paused during the third neoadjuvant treatment). Each cycle lasts for three weeks.

Neobrave

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Regional multiple lymph node metastases or fusion, retroperitoneal lymph node metastases;
• Peritoneal metastasis, distant metastasis;
• Previous systemic treatment, including but not limited to chemotherapy, targeted therapy, immunotherapy;
• Previous local treatment, including but not limited to HAIC, TACE, TARE, ablation, radiotherapy, etc.;
• Severe hepatic artery variation;
• Allergy to contrast agents;
• Allergy to oxaliplatin;
• Vaccination with live attenuated vaccine within 4 weeks prior to first administration or planned during the study period;
• Presence of \> grade 1 peripheral neuropathy;
• Presence of any active autoimmune disease or history of autoimmune disease;
• Complication of other malignancies (except for basal cell or squamous cell skin cancer or cervical carcinoma in situ that was treated curatively);
• Human immunodeficiency virus (HIV) infection or known acquired immune deficiency syndrome (AIDS);
• 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;
• Hypertension that cannot be well controlled with antihypertensive medications (systolic blood pressure ≥140 mmHg or diastolic pressure ≥90 mmHg);
• Abnormal coagulation function (INR\>1.5 or APTT\>1.5×ULN), with bleeding tendency or currently undergoing thrombolytic therapy, anticoagulant therapy, or antiplatelet therapy;

Sponsors & Collaborators

• Peking University: lead

Study Sites (1)

Peing University Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Related Publications (30)

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MeSH Terms

Conditions

Cholangiocarcinoma; Cirrhosis, Familial, with Pulmonary Hypertension; Klatskin Tumor

Interventions

gemcitabine-oxaliplatin regimen; Fluorouracil

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Xiaodong Wang, M.D.

  Peking University Cancer Hospital & Institute

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2024
• First Posted: December 18, 2024
• Study Start: December 31, 2024
• Primary Completion: December 22, 2025
• Study Completion: December 22, 2025
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)