Trial Title:
Neoadjuvant Therapy of HAIC（GEMOX） Combined With Adebrelimab and Lenvatinib for Resectable Intrahepatic Cholangiocarcinoma With High-risk Recurrence Factors
NCT ID:
NCT06208462
Condition:
Intrahepatic Cholangiocarcinoma
Conditions: Official terms:
Cholangiocarcinoma
Recurrence
Gemcitabine
Oxaliplatin
Lenvatinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Adebrelimab
Description:
1200mg，i.v. , q3w
Arm group label:
Combined treatment group
Other name:
SHR-1316
Intervention type:
Drug
Intervention name:
Lenvatinib
Description:
8mg,qd
Arm group label:
Combined treatment group
Other name:
4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxamide
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
800 mg/m2，q3w
Arm group label:
Combined treatment group
Other name:
Difluorodeoxycytidine Hydrochloride
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
85 mg/m2，q3w
Arm group label:
Combined treatment group
Other name:
Diaminocyclohexane Oxalatoplatinum
Summary:
Clinical Study on the efficacy and safety of HAIC（GEMOX）and Lenvatinib combined with
Adebrelimab neoadjuvant therapy for resectable Intrahepatic Cholangiocarcinoma with
high-risk recurrence factors.
Detailed description:
Intrahepatic cholangiocarcinoma (ICC) accounts for more than 20% of hepatic malignancies
and has become the second most common primary liver tumor worldwide. The incidence of ICC
is increasing annually, showing a trend to affecting younger individuals. Treatment
options for ICC contain surgical resection, perioperative chemotherapy, liver-directed
therapies and systemic therapy such as cytotoxic therapy, targeted therapy and
immunotherapy. Adjuvant chemotherapy after ICC resection has become the standard for
patients with resected ICC based on the BILCAP trial with better mOS (53 months vs. 36
months, p=0.028) and RFS (25.9 months vs. 17.4 months, p=0.0093). The rationale for
neoadjuvant chemotherapy for patients with resectable ICC also suggests a potential
advantage according to NEO-GAP. While the effectiveness of hepatic artery infusion
chemotherapy (HAIC) has been proven in unresectable ICC, its role in resectable ICC is
controversial. The TOPAZ-1 trial demonstrated the efficacy of immune checkpoint blockade
in ICC. However, it remains to be seen whether combined therapy above is effective in
resectable ICC.
Surgical resection remains the mainstay for ICC therapy, but postoperative patients often
have a high tumor recurrence rate. The median time of disease-free survival is 18.5
months, and recurrence rate is 60%-65%. Previous research suggests that the prognosis of
ICC depends on several risk factors for recurrence consisting of Stage ≥ Ib (AJCC 8th),
tumor size > 5cm, multiple tumor lesions in the same lobe, presence of radiographic major
vascular invasion, or lymph node involvement, technically resectable. Further
investigation is needed to evaluate the effectiveness of the comprehensive treatment
system, which includes HAIC (GEMOX), immunotherapy, neoadjuvant therapy, and surgical
resection, for ICC with high-risk recurrence factors.
The goal of this clinical trial is to assess the efficacy and safety of HAIC (GEMOX) and
Lenvatinib combined with Adebrelimab neoadjuvant therapy for resectable ICC with
high-risk recurrence factors. The primary end point is to evaluate the recurrence free
survival (RFS) of patients after treatment, and the second outcome measures include
overall survival (OS), objective response rate (ORR) and pathological complete response
(pCR). In order to investigate more effective ICC therapies, participants will undergo
2-4 cycles of HAIC (GEMOX) in combination with Lenvatinib and Adebrelimab. Evaluation
will be conducted every 2 cycles, and surgery will be performed when qualified.
Capecitabine will be administered for 1-14 days after surgery, and regular follow-up will
be conducted.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. The patient must sign the informed consent;
2. Age 18-75 years old, male and female;
3. ECOG Physical status Score (PS score) 0 or 1;
4. Patients with ICC who have been pathologically diagnosed (histopathological and/or
cytological examination) or clinically diagnosed as having high-risk factors;
Risk factors are defined as follows:
Stage ≥Ib, single lesion > 5cm, multiple tumor lesions in the same lobe, technically
resectable;Vascular invasion, regional lymph node metastasis, technically resectable
5. Patients with untreated and resectable locally advanced ICC who have been assessed
by the surgeon as surgically resectable;
6. The functional indicators of vital organs meet the following requirements
① Neutrophils ≥1.5*109/L; Platelet ≥80*109/L; Hemoglobin ≥9g/dl; Serum albumin
≥3g/dl;② Thyroid stimulating hormone (TSH) ≤ 1 times the upper limit of normal, T3,
T4 in the normal range;③ Bilirubin ≤ 1.5 times the upper limit of normal value; ALT
and AST≤ 2 times the upper limit of normal value;④ Serum creatinine ≤ 1.5 times the
upper limit of normal value, creatinine clearance ≥60 ml/min;
7. The subject has at least one measurable lesion (according to RECIST1.1);
8. Fertile women: must agree to abstain from sex (abstain from heterosexual
intercourse) or use a reliable, effective method of contraception for at least 120
days from the signing of the informed consent until the final administration of the
study drug. Serum HCG test must be negative within 72 hours before randomization.
And must be non-lactating.A woman is considered fertile if she has menstruated, has
not yet reached postmenopausal status (no continuous periods for ≥12 months, no
cause other than menopause has been found), and has not undergone sterilization
(such as hysterectomy, bilateral tubal ligation, or bilateral oophorectomy).
9. For male subjects whose partner is a fertile woman, they must agree to abstain from
sex or use a reliable, effective method of contraception for at least 120 days from
the signing of the informed consent until the final administration of the study
drug. Male subjects also had to agree not to donate sperm during the same time
period. Male subjects with a pregnant partner are required to use condoms and do not
need to use other methods of contraception.
Exclusion Criteria:
1. Pathological diagnosis of hepatocellular carcinoma, mixed hepatocellular carcinoma
and other non-cholangiocarcinoma malignant tumor components;
2. Prior systemic therapy and tumor-related surgical treatment (biliary drainage
allowed);Patients who relapse after surgery, have received PD1 antibody, PDL1
antibody or CTLA4 antibody, Lenvatinib, chemotherapy in the past; participated in
other clinical trials 30 days before screening
3. Previous or co-existing malignancies other than adequately treated non-melanin skin
cancer, cervical carcinoma in situ and thyroid papillary carcinoma;
4. Active pulmonary tuberculosis infection. Patients with active pulmonary tuberculosis
infection within 1 year prior to enrollment; Had a history of active tuberculosis
infection more than 1 year before enrollment, had not received formal
anti-tuberculosis therapy or had active tuberculosis;
5. Have an active, known, or suspected autoimmune disease. Subjects with hypothyroidism
requiring hormone replacement therapy and skin conditions that do not require
systemic therapy are eligible;
6. Long-term acceptance of systemic sex hormones (doses equivalent to > 10mg
prednisone per day) or any other form of immunosuppressive therapy. Participants
using inhaled or topical corticosteroids may be enrolled;
7. Severe cardiopulmonary and renal dysfunction;
8. Have hypertension that is not well controlled by antihypertensive medication
(systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg);
9. Abnormal coagulation function (PT> 14s), have a tendency to bleed or are
receiving thrombolytic or anticoagulant therapy;
10. HBV DNA> 2000IU/ml, HCV RNA> 1000 IU/ml;
11. Had clinically significant bleeding symptoms or a clear tendency to appear within 3
months before enrollment;
12. Active infections that require systemic treatment;
13. Human immunodeficiency virus (HIV, HIV1/2 antibodies) positive;
14. Have a history of psychotropic substance abuse, alcohol abuse or drug use;
15. Have a history of drug allergy;
16. Other factors, as determined by the investigator, that may affect the subject's
safety or compliance with the test. Such as a serious illness (including mental
illness) requiring co-treatment, serious laboratory abnormalities, or other family
or social factors.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The First Affiliated Hospital of Nanjing Medical University
Address:
City:
Nanjing
Country:
China
Status:
Recruiting
Contact:
Last name:
Feng Cheng
Start date:
March 25, 2024
Completion date:
January 2027
Lead sponsor:
Agency:
The First Affiliated Hospital with Nanjing Medical University
Agency class:
Other
Collaborator:
Agency:
Jiangsu Hengrui Pharmaceutical Co., Ltd.
Agency class:
Industry
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/NCT06208462
