Clinical trial NCT05430698: PD-1 Antibody Plus GEMOX as Postoperative Adjuvant Therapy in Perihilar Cholangiocarcinoma
Official title: PD-1 Antibody Plus Gemcitabine and Oxaliplatin (GEMOX) as Postoperative Adjuvant Therapy in Perihilar Cholangiocarcinoma Patients With Positively Metastatic Lymph Nodes : a Single Arm, Phase II Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Perihilar Cholangiocarcinoma
Keywords: PD-1
GEMOX
Perihilar Cholangiocarcinoma
Positively Metastatic Lymph Nodes
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2022-06-24
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: The 12-month relapse-free survival rate
timeFrame: 12 months
Secondary outcomes:
measure: The 12-month overall survival rate
timeFrame: 12 months
measure: The 60-month overall survival rate
timeFrame: 60 months
measure: Relapse-free survival
timeFrame: 60 months
measure: Overall survival
timeFrame: 60 months
measure: Percentage of participants with adverse events (AEs)
timeFrame: 12 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: Department of Biliary and Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University
name: Chao Liu, PhD
role: PRINCIPAL_INVESTIGATOR
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