Neoadjuvant Therapy of HAIC（GEMOX） Combined With Adebrelimab and Lenvatinib for Resectable Intrahepatic Cholangiocarcinoma With High-risk Recurrence Factors

Intrahepatic Cholangiocarcinoma Clinical Trial

Official title:

Neoadjuvant Therapy of HAIC（GEMOX） Combined With Adebrelimab and Lenvatinib for Resectable Intrahepatic Cholangiocarcinoma With High-risk Recurrence Factors：NEO-ERA-01 Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06208462
• Other study ID #: NEO-ERA-01
• Status: Recruiting
• Phase: Phase 2
• Start date: March 25, 2024
• Est. completion date: January 2027

Study information

• Verified date: March 2024
• Source: The First Affiliated Hospital with Nanjing Medical University
• Contact: Feng Cheng, MD
• Phone: 13305170695
• Email: docchengfeng[@]njmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 33
• Est. completion date: January 2027
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

? Neutrophils =1.5*109/L; Platelet =80*109/L; Hemoglobin =9g/dl; Serum albumin =3g/dl;? Thyroid stimulating hormone (TSH) = 1 times the upper limit of normal, T3, T4 in the normal range;? Bilirubin = 1.5 times the upper limit of normal value; ALT and AST= 2 times the upper limit of normal value;? 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.

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Intrahepatic Cholangiocarcinoma
• Recurrence

Intervention

Drug:
• Adebrelimab
1200mg,i.v. , q3w
• Lenvatinib
8mg,qd
• Gemcitabine
800 mg/m2,q3w
• Oxaliplatin
85 mg/m2,q3w

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
The First Affiliated Hospital with Nanjing Medical University	Jiangsu Hengrui Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR	Objective Response Rate (ORR)	one year
Secondary	Assess safety and tolerability	Assess safety and tolerability of HAIC(GEMOX)and Lenvatinib combined with Adebrelimab neoadjuvant therapy	one year
Secondary	OS	Overall survival (OS)	one year
Secondary	pCR	Pathological Complete Response (pCR)	one year
Secondary	PFS	Progression-free survival (PFS)	one year
Secondary	R0 resection rate	The percentage of patients received R0 resection after HAIC(GEMOX)and Lenvatinib combined with Adebrelimab neoadjuvant therapy	one year
Secondary	Surgical rate	The surgical rate of patients after HAIC(GEMOX)and Lenvatinib combined with Adebrelimab neoadjuvant therapy	one year