Neoadjuvant therapy for high-risk intrahepatic cholangiocarcinoma patients

Tislelizumab Combined with GEMOX (GOT) Applied As Neoadjuvant Regimen for Patients of Resectable Intrahepatic Cholangiocarcinoma with High-risk Factors of Recurrence: a Single Arm, Single Center, Prospective, Explorative Clinical Trail.

This study is testing a new combination treatment for patients with high-risk intrahepatic cholangiocarcinoma to see if it can improve their chances of successful surgery and survival.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Zhejiang Cancer Hospital (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, Prednisone, Tislelizumab
• Locations: 2 sites (Hangzhou, Zhejiang and 1 other locations)
• Trial ID: NCT05557578 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of Tislelizumab combined with the GEMOX regimen as a neoadjuvant therapy for patients with resectable intrahepatic cholangiocarcinoma (ICC) who exhibit high-risk factors for recurrence. The study aims to evaluate the objective response rate, R0 resection rate, and overall survival of participants. Patients eligible for this trial must have never received systemic therapy and meet specific criteria related to tumor size, CA19-9 levels, and other clinical factors. The goal is to enhance treatment outcomes for this aggressive cancer type.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with pathologically confirmed resectable ICC and specific high-risk recurrence factors.

Not a fit: Patients who have previously received systemic therapy or have non-resectable tumors will not benefit from this study.

Why it matters

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

How similar studies have performed: Other studies have shown promising results with similar neoadjuvant therapies in aggressive cancers, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. 18-75 yo;
2. Patients of Pathological confirmed intrahepatic cholangiocarcinoma who has never received systemic therapy including chemotherapy, immunotherapy, target therapy and other anti-cancer therapy;
3. Patients of resectable ICC with high risk recurrent factors:

   ①Maximum diameter greater than 5cm or multiple tumors.

   ②Preoperative CA19-9 greater than 200 Unit(U)/mL

   ③Tumors invaded adjacent blood vessels

   ④Preoperative radiology hints suspected regional lymph node metastasis.

   ⑤Tumor tissues confirmed by CT or MRI, at least one measurable lesion exists according to RECIST v1.1.
4. Eastern Cooperative Oncology Group(ECOG)-Performance status(PS) score is 0 before first drug administration;
5. Child-Pugh classification is class A;
6. Estimated overall survival is greater than 16 weeks;
7. The level of organ function meets the criteria and can tolerate surgery before the first treatment. Main organs meet the criteria as below:

   haemoglobin≥90g/L，Neutrophil count≥1.5×10⁹/L，Platelet count≥100×10⁹/L；Aspartate or alanine aminotransferase≤5 upper limits of normal(ULN），alkaline phosphatase≤2.5 ULN，Serum albumin≥30g/L；serum creatinine\<1.5 ULN；International normalized ratios（INR）≤2 or Prothrombin time（PT）exceed ULN≤6s；Creatinine clearance≥60 mL/min.
8. Male and female subjects with potential fertility had to agree to the use of effective contraceptive methods throughout the study period；
9. Sign an informed consent form agreeing to provide previously preserved specimens of tumor tissue or fresh detection of tumor lesions.

Exclusion Criteria:

1. Patient with non-intrahepatic cholangiocarcinoma；
2. Anti-cancer therapy or surgery such as radiotherapy, radiofrequency ablation, interventions in 28 days prior to the first dose of the study (except for previous non-tumor-related surgeries and diagnostic biopsies)；
3. Distant metastasis；
4. hepatitis B virus (HBV) DNA\>2000 copies/ml, hepatitis C virus (HCV) RNA\>1000;
5. Long-term glucocorticoid users require long-term systemic hormones (equivalent to \>10 mg Prednisone/day) or any other form of immunosuppressive therapy；
6. Clinically significant bleeding or bleeding tendencies within 3 months prior to enrollment or on thrombolytic or anticoagulant therapy；
7. Patients with complete bowel obstruction and incomplete intestinal obstruction that require treatment, but patients who have been relieved of obstruction by ostomy or stent placement can be enrolled；
8. Active severe clinical infections (\> grade 2, NCI-CTCAE version 5.0), including active TB; Have a history of active TB infection at least 1 year before enrolment, have not received regular anti-tuberculosis (TB) treatment or are still active; active, known or suspected autoimmune disease;
9. Uncontrolled diabetes mellitus (fasting blood glucose ≥10 mmol/L), severe lung disease (eg, acute lung disease, pulmonary fibrosis that affects lung function, interstitial lung disease). except for recovered radiation pneumonia);
10. Clinically significant cardiovascular diseases; With hypertension, antihypertensive drugs cannot be well controlled (systolic blood pressure≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg);
11. Patient who are receiving renal replacement therapy；
12. History of other malignancies in the last 5 years. With the exception of carcinoma of the skin basal cells that have been cured or carcinoma in situ in the cervix;
13. Others situations are not expected to tolerate surgical treatment；
14. People with allergic reactions to any component of the drug under study;
15. There are other unsuitable candidates for clinical trials, such as alcohol dependence, mental illness, pregnancy (or lactation).

Where this trial is running

Hangzhou, Zhejiang and 1 other locations

• 1# Banshan East Rd. Zhejiang cancer hospital — Hangzhou, Zhejiang, China (NOT_YET_RECRUITING)
• Jia Wu — Hanzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Chaoqun Fei

Conditions: Intrahepatic Cholangiocarcinoma, Tislelizumab, Gemcitabine, Oxaliplatin, cholangiocarcinoma, Neoadjuvant