Combining Adebrelimab with Capecitabine for High-Risk Cholangiocarcinoma After Surgery

A Phase 2, Randomized, Controlled, Multicenter Study of Adjuvant Adebrelimab Combined With Capecitabine in Resected Cholangiocarcinoma With High-risk Factors: ACHIEVE

This study is testing if combining a new immunotherapy drug with a chemotherapy drug can help prevent cancer from coming back in adults with high-risk cholangiocarcinoma after surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 122 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, Adebrelimab
• Locations: 4 sites (Nanjing, Jiangsu and 3 other locations)
• Trial ID: NCT06607276 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of combining Adebrelimab, an immunotherapy agent, with capecitabine, a chemotherapy drug, as an adjuvant treatment for patients with high-risk cholangiocarcinoma who have undergone surgical resection. The study aims to reduce the recurrence of cancer post-surgery and improve overall survival rates. Eligible participants include adults aged 18-75 with specific high-risk factors for recurrence, and they must have no evidence of metastatic disease. The trial will assess the safety and efficacy of this combination therapy compared to standard treatment options.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with histologically confirmed high-risk cholangiocarcinoma who have undergone R0 resection.

Not a fit: Patients with recurrent or metastatic cholangiocarcinoma or those who have received prior systemic anti-cancer therapy will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of cancer recurrence and improve survival rates for patients with high-risk cholangiocarcinoma.

How similar studies have performed: Previous studies have shown promising results with adjuvant therapies in cholangiocarcinoma, but this specific combination of Adebrelimab and capecitabine is being explored for the first time.

Eligibility criteria

Inclusion Criteria:

1. Patients must sign an informed consent form;
2. Ages 18-75, both genders eligible;
3. ECOG performance status score (PS score) of 0 or 1;
4. Patients with histologically confirmed cholangiocarcinoma (including intrahepatic cholangiocarcinoma and hilar cholangiocarcinoma), who have undergone R0 resection and have high-risk factors for recurrence;

   High-risk factors are defined as follows:

   Intrahepatic cholangiocarcinoma ( Single tumor \> 5 cm, multiple tumors, liver capsule breach, vascular invasion, regional lymph node metastasis) Hilar cholangiocarcinoma (Tumor invasion into surrounding tissues, vascular invasion, regional lymph node metastasis)
5. No evidence of recurrence or metastatic lesions on imaging within 28 days prior to randomization;
6. No prior systemic anti-cancer therapy (including radiotherapy, chemotherapy, targeted therapy, immunotherapy) before curative resection;
7. Laboratory test values within 7 days prior to the first dose of study medication meet the following criteria:

   Complete blood count: (except for hemoglobin, no blood transfusion or use of granulocyte colony-stimulating factor \[G-CSF\], no medication correction within 2 weeks prior to screening):

   Absolute neutrophil count ≥1.5×109/L; Platelets ≥75×109/L; Hemoglobin ≥90 g/L;

   Biochemical tests:

   Serum albumin ≥30g/L; Serum total bilirubin ≤1.5×ULN; ALT and AST ≤3×ULN; Serum creatinine ≤1.5×ULN; or Cr clearance rate \>50 mL/min International normalized ratio (INR) ≤1.2 or prothrombin time (PT) exceeding the normal control range by ≤2 seconds; Urine protein \<2+ (if urine protein ≥2+, a 24-hour (h) urine protein quantification can be performed, and a 24h urine protein quantification of \<1.0g is eligible for enrollment);
8. Life expectancy of more than 6 months.

Exclusion Criteria:

1. Pathological diagnosis of mixed hepatocellular carcinoma and other non-hepatic extra-bile duct cholangiocarcinoma or ampulla of Vater malignant tumor components;
2. History of prior systemic treatment;
3. History of or concurrent other malignancies, excluding non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma that have been adequately treated;
4. Active tuberculosis infection. Patients with active tuberculosis infection within 1 year prior to enrollment; history of active tuberculosis infection more than 1 year prior to enrollment without proper anti-tuberculosis treatment or tuberculosis is still active;
5. History of autoimmune diseases or immunodeficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener\'s granulomatosis, Sjogren\'s syndrome, Guillain-Barre syndrome, or multiple sclerosis;
6. Requirement for long-term systemic corticosteroids (dosage equivalent to \>10mg prednisone/day) or any other form of immunosuppressive treatment. Subjects using inhaled or topical corticosteroids may be included;
7. Severe cardiopulmonary or renal dysfunction;
8. Inadequately controlled arterial hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) (based on the average of ≥2 blood pressure readings), allowing the achievement of the above parameters through the use of antihypertensive treatment; history of hypertensive crisis or hypertensive encephalopathy;
9. Within 3 months prior to enrollment, significant clinical bleeding symptoms or a clear tendency to bleed; abnormal coagulation function (PT \>14s), tendency to bleed, or undergoing thrombolytic or anticoagulant therapy;
10. HBV DNA \>2000 IU/ml, active HCV infection (positive HCV antibody and HCV-RNA level above the lower limit of detection);
11. Active infection requiring systemic treatment;
12. Human immunodeficiency virus (HIV, HIV1/2 antibody) positive;
13. History of psychiatric medication abuse, alcoholism, or drug addiction;
14. History of allergy to study medication;
15. Other factors deemed by the investigator to potentially affect subject safety or trial compliance. Such as severe diseases requiring concurrent treatment (including psychiatric diseases), severe laboratory test abnormalities, or other family or social factors.

Where this trial is running

Nanjing, Jiangsu and 3 other locations

• Jinling Hospital — Nanjing, Jiangsu, China (Not_yet_recruiting)
• The First Affiliated Hospital of Nanjing Medical University — Nanjing, Jiangsu, China (Recruiting)
• The Affiliated Hospital of Xuzhou Medical University — Xuzhou, Jiangsu, China (Not_yet_recruiting)
• Yancheng NO.1 People's Hospital — Yancheng, Jiangsu, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Xiangcheng Li, Prof. M.D.

Conditions Cholangiocarcinoma Cancer; Adebrelimab; capecitabine; Cholangiocarcinoma; Adjuvant Therapy