PD-1 Antibody Plus GEMOX as Postoperative Adjuvant Therapy in Perihilar Cholangiocarcinoma

NCT ID: NCT05430698

Last Updated: 2023-05-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-31
• Study Completion Date: 2025-10-08

Brief Summary

This is an open-label,single center,non-randomized,single arm exploratory study. The objective of this study is to evaluate the efficacy and safety of PD-1 antibody plus GEMOX as postoperative adjuvant therapy in perihilar cholangiocarcinoma with positively metastatic lymph nodes.

Detailed Description

For perihilar cholangiocarcinoma, radical surgical treatment, such as major hepatectomy combined with total caudate lobe and extrahepatic bile duct resection, remain the potential modality for cure. However, the lymph node tumor metastasis is an independent risk factor for prognosis after radical resection for this disease without distant metastasis. As reported by Nagoya University, Japan, the patients without lymph node tumor metastasis, the 5-year survival rate could reach as high as 67.1% after R0 resection, but the 5-year survival rate was only 22.1% for the patients with lymph node tumor metastasis after R0 resection. Thus, it is urgent to look for an effective adjuvant therapy treatment for these patients with lymph node tumor metastasis. Fluoropyrimidine-based or gemcitabine-based chemotherapy was recommended for these patients by NCCN guidelines. Studies have shown that Gemox chemotherapy (oxaliplatin + gemcitabine) in patients with resected biliary tract cancer has a good benefit in overall survival. However, for extrahepatic cholangiocarcinoma with lymph nodes metastasis, the benefit was limited. In recent years, immunotherapy, such as PD-1 or PD-L1 monoclonal antibody, combined with chemotherapy have shown better results in the palliative treatment of un-resectable biliary tract tumor. However, there is no report on combined immunotherapy with chemotherapy as adjuvant therapy in perihilar cholangiocarcinoma with lymph node tumor metastasis after R0 resection.

Conditions

Perihilar Cholangiocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

PD-1antibody plus GEMOX

PD-1 antibody plus GEMOX was given as postoperative adjuvant therapy

Group Type: EXPERIMENTAL

PD-1antibody plus GEMOX

Intervention Type: DRUG

1. PD-1 antibody，200mg，D1，intravenous infusion, the administration time is 60 (+15) minutes.

2. GEMOX chemotherapy : gemcitabine 1000mg/m2,D1，D8；oxaliplatin 100mg/m2,D1，intravenous infusion.

3. Three weeks is a course of treatment,a total of 6-8 courses.

Interventions

PD-1antibody plus GEMOX

1. PD-1 antibody，200mg，D1，intravenous infusion, the administration time is 60 (+15) minutes.

2. GEMOX chemotherapy : gemcitabine 1000mg/m2,D1，D8；oxaliplatin 100mg/m2,D1，intravenous infusion.

3. Three weeks is a course of treatment,a total of 6-8 courses.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. The patient must sign an informed consent form;

2. Age 18-75 years old, both male and female;

3. ECOG performance status score (PS score) 0 or 1 point;

4. Child-Pugh score A period;

5. Perihepatic cholangiocarcinoma with negative margins and positively metastatic lymph nodes confirmed by histopathology. Abdominal positively metastatic lymph nodes region is not limited. The 16 groups of microscopically positively metastatic lymph nodes can be included.

6. Have not received any systemic treatment within 6 months;

7. The functional indicators of important organs meet the following requirements (1)Neutrophils≥1.5*109/L; platelets≥100*109/L; hemoglobin≥9g/dl; serum albumin≥3g/dl; (2)Thyroid-stimulating hormone (TSH) ≤ 2 times the upper limit of normal, and T3 and T4 are in the normal range; (3)Bilirubin ≤ 1.5 times the upper limit of normal; ALT and AST ≤ 3 times the upper limit of normal; (4)Serum creatinine ≤ 1.5 times the upper limit of normal, and creatinine clearance ≥ 60ml/min (calculated by Cockcroft-Gault formula); 8. The subject has at least 1 measurable lesion (according to RECIST1.1);

8. For women who are not breastfeeding or pregnant, use contraception during treatment or 12 months after the end of treatment.

Exclusion Criteria

1. Unresectable PHC patients or postoperative diagnosis of PHC recurrence and metastasis ;

2. Past or simultaneous suffering from other malignant tumors, except for fully treated non-melanoma skin cancer, cervical carcinoma in situ, and thyroid papillary carcinoma;

3. Have used gemcitabine-based chemotherapy or have used PD-1 monoclonal antibody or PD-L1 monoclonal antibody treatment within 6 months;

4. Severe cardiopulmonary and renal dysfunction;

5. Hypertension that is difficult to control with drugs (systolic blood pressure (BP) ≥140 mmHg and/or diastolic blood pressure ≥90mmHg) (based on the average of ≥3 BP readings obtained by ≥2 measurements);

6. Abnormal coagulation function (PT>14s), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy;

7. After antiviral treatment, HBV DNA>2000 copies/ml, HCV RNA>1000;

8. A history of esophageal and gastric varices, significant clinically significant bleeding symptoms or a clear tendency to appear within 3 months before enrollment;

9. Active infections requiring systemic treatment; patients with active tuberculosis infection within 1 year before enrollment; a history of active tuberculosis infection more than 1 year before enrollment, and no formal anti-tuberculosis treatment or tuberculosis Still in the active period;

10. Human immunodeficiency virus (HIV, HIV1/2 antibody) positive;

11. A history of psychotropic drug abuse, alcohol or drug abuse;

12. Known to have a history of severe allergies to any monoclonal antibodies, platinum drugs, or gemcitabine;

13. Other factors judged by the investigator may affect the safety of the subjects or the compliance of the trial. Such as serious diseases (including mental illness) that require combined treatment, serious laboratory abnormalities, or other family or social factors.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chao Liu, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Biliary and Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Locations

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Rui Zhang, PhD

Role: CONTACT

zhangr95@mail.sysu.edu.cn

020-34078840

Yanfang Ye

Role: CONTACT

yeyfang@mail.sysu.edu.cn

020-81336505

Facility Contacts

Rui Zhang, PhD

Role: primary

zhangr95@mail.sysu.edu.cn

020-34078840

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Other Identifiers

LX-GY-2022010

Identifier Type: -

Identifier Source: org_study_id