Trial Title:
Adebrelimab Combined With Capecitabine for Adjuvant Therapy in Cholangiocarcinoma With High-risk Recurrence Post-surgery
NCT ID:
NCT06607276
Condition:
Cholangiocarcinoma Cancer
Adebrelimab (SHR-1316)
Conditions: Official terms:
Cholangiocarcinoma
Recurrence
Capecitabine
Conditions: Keywords:
Adebrelimab
Postoperative adjuvant therapy
capecitabine
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Adebrelimab and capecitabine
Description:
Adebrelimab：1200mg, iv, q3w capecitabine:1250mg/m2, po, bid,treat for 2 weeks and rest
for 1 week
Arm group label:
Adebrelimab and capecitabine
Intervention type:
Drug
Intervention name:
capecitabine
Description:
capecitabine:1250mg/m2, po, bid,treat for 2 weeks and rest for 1 week
Arm group label:
capecitabine
Summary:
Biliary tract malignancies (BTC) are malignant tumors that originate from the epithelium
of the bile ducts. Currently, the optimal treatment for biliary tract malignancies is
radical surgical resection. In recent years, with the advancement of imaging technology
and surgical techniques, there has been certain progress in the diagnosis and treatment
of biliary tract malignancies. However, the surgical resection rate and long-term
survival rate after surgery are still not satisfactory, and the high postoperative
recurrence rate is an important factor affecting the long-term survival of patients.
Therefore, there is an urgent need to explore new postoperative adjuvant treatment plans
to reduce postoperative tumor recurrence, which is of great significance for extending
the survival of patients with biliary tract malignancies. In the NCCN and CSCO
guidelines, capecitabine is listed as a category I recommendation for adjuvant treatment
of biliary tract malignancies (BTC). However, in clinical practice, the use of
capecitabine or tegafur for postoperative patients with cholangiocarcinoma at high risk
of recurrence still has a high recurrence rate. Therefore, there is still a huge unmet
need in the clinical adjuvant treatment after surgery for biliary tract malignancies.
Based on the above background, we plan to carry out a randomized, open, and comparative
study to observe the efficacy and safety of Adebrelimab combined with capecitabine for
adjuvant treatment in patients with biliary tract malignancies after surgery, and to
explore treatment methods to improve the efficacy of postoperative adjuvant treatment for
cholangiocarcinoma.
Detailed description:
Postoperative adjuvant therapy for biliary system tumors has long lacked a universally
recognized standard regimen. The BILCAP trial results showed a survival benefit with
adjuvant therapy. The BILCAP study filled the gap in the field of postoperative adjuvant
therapy for biliary system tumors. In the study, the median overall survival (OS) in the
capecitabine group was 51.1 months, compared to 36.4 months in the observation group. The
median recurrence-free survival (RFS) in the capecitabine group was 24.4 months, compared
to 17.5 months in the observation group. Compared to the observation group, adjuvant
therapy with capecitabine significantly prolonged both OS and RFS, and the capecitabine
group had good tolerability with no chemotherapy-related deaths. In addition, the ASCOT
study reported that adjuvant therapy with tegafur after surgery could prolong the RFS
rate in patients. Therefore, in the NCCN and CSCO guidelines, capecitabine is listed as a
category I recommendation for adjuvant therapy of biliary tract malignancies (BTC).
However, it is regrettable that the latest reports show that in the intention-to-treat
(ITT) population, the BILCAP trial failed to reach its primary endpoint of OS, with the
median OS in the study group and the control group being 51.1 months and 36.4 months,
respectively [HR=0.81, 95% CI(0.63,1.04), P=0.097]. Furthermore, in clinical practice,
the use of capecitabine or tegafur after surgery in patients with cholangiocarcinoma at
high risk of recurrence still has a high recurrence rate. Therefore, there is still a
significant unmet need in the clinical postoperative adjuvant therapy for biliary tract
malignancies.Based on the above background, we plan to carry out a randomized, open, and
comparative study to observe the efficacy and safety of Adebrelimab combined with
capecitabine for adjuvant treatment in patients with biliary tract malignancies after
surgery, and to explore treatment methods to improve the efficacy of postoperative
adjuvant treatment for cholangiocarcinoma.
Criteria for 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 >5cm, multiple tumors within
the liver, tumor penetration of the liver capsule or direct involvement of
surrounding tissue, vascular invasion, regional lymph node metastasis) Hilar
cholangiocarcinoma (tumor infiltration of surrounding tissue or adjacent liver
parenchyma, 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
September 20, 2024
Completion date:
September 20, 2027
Lead sponsor:
Agency:
The First Affiliated Hospital with Nanjing Medical University
Agency class:
Other
Source:
The First Affiliated Hospital with Nanjing Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06607276
