Phase II-III Clinical Trial of PD1 Antibody (Toripalimab), Lenvatinib and GEMOX Neoadjuvant Treatment for Resectable Intrahepatic Cholangiocarcinoma With High-risk Recurrence Factors

NCT04669496 | Active Not Recruiting Phase 2

• 1 other identifier: ZSAB-neoGOLP
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 1

Brief Summary

A randomized controlled, multicenter, open, seamless phase II-III clinical trial is designed to target patients with resectable intrahepatic cholangiocarcinoma with high-risk recurrence factors which has extremely low postoperative recurrence-free survival. In this study, we aim to compare the prognosis in intrahepatic cholangiocarcinoma between Toripalimab combined with leventinib and GEMOX neoadjuvant treatment and the current clinical surgical treatment (traditional group).

Conditions

Intrahepatic Cholangiocarcinoma; PD1 Antibody; Lenvatinib; Gemox Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Event-free survival

  From randomization to the occurrence of the following events: disease progression prevents radical surgery; local or distant recurrence; second primary tumor; death due to various causes.

  24 months

Secondary Outcomes (6)

• Overall survival

  24 months

• Objective response rate

  6 months

• Pathological remission rate

  6 months

• Adverse events

  12 months

• R0 Resection Rate

  12 months

Other Outcomes (1)

• Exploratory markers

  24 months

Study Arms (2)

Neoadjuvant treatment

EXPERIMENTAL

1. Gemox chemotherapy D1 Oxaliplatin 85mg/m2+ gemcitabine 1g/m2, D8 gemcitabine 1g/m2 Three weeks is a course of treatment, a total of 3 courses. 2. Lenvatinib (8mg/d) for 9 weeks of continuous use. 3. Toripalimab (240 mg, once every 3 weeks), used 3 times in a row. All patients undergoing resection use capecitabine 1250mg/m2 twice a day for 2 weeks, stopping for 1 week as a course of treatment, totaling 8 courses.

Drug: Neoadjuvant treatment

Traditional group

NO INTERVENTION

No anti-tumor drug treatment before surgery. All patients after resection use capecitabine 1250mg/m2 twice a day for 2 weeks, stopping for 1 week as a course of treatment, a total of 8 courses.

Interventions

Neoadjuvant treatment DRUG

PD1 antibody (Toripalimab) combined with GEMOX chemotherapy and Lenvatinib neoadjuvant treatment

Neoadjuvant treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) Sign written informed consent 2) Male or female patients aged 18-70; 3) ECOG score 0 points, Child-Pugh rating A; 4) Pathological diagnosis by biopsy: Intrahepatic cholangiocarcinoma (ICC). 5) Resectable ICC patients with high risk factors for recurrence (tumor diameter\>5cm or imaging vascular invasion, multiple tumor nodules or hilar lymph node metastasis or Preoperative CA19-9 \>37 U/mL or above the upper limit of normal (for centers where the normal range is not \<37 U/mL); 6) The functional indicators of important organs meet the following requirements
• Neutrophils≥1.5\*109/L; platelets≥90\*109/L; hemoglobin≥9g/dl; serum albumin≥3.5g/dl;
• Coagulation function: International standardization (prothrombin time) ratio (INR) \<1.2;
• T3 and T4 do not exceed the normal upper and lower limits by 2 times;
• Bilirubin ≤ 1.5 times the upper limit of normal; ALT and AST ≤ 3 times the upper limit of normal;
• Serum creatinine ≤ 1.5 times the upper limit of normal, creatinine clearance ≥ 60ml/min; 7) The subject has at least 1 measurable liver disease (according to RECIST1.1); 8) For women who are not breastfeeding or pregnant, use contraception during treatment or 3 months after the end of treatment.

You may not qualify if:

• \) Pathological diagnosis of hepatocellular carcinoma, mixed hepatocellular carcinoma and other non-biliary cell carcinoma malignant tumor components; 2) 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) Past or simultaneous suffering from other malignant tumors, except for fully treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary carcinoma; 4) Active tuberculosis infection. Patients with active tuberculosis infection within 1 year before enrollment; a history of active tuberculosis infection more than 1 year before enrollment, no formal anti-tuberculosis treatment or tuberculosis is still active; 5) Suffer from active, known or suspected autoimmune diseases. Subjects with hypothyroidism who only need hormone replacement therapy and skin diseases without systemic therapy can be selected; 6) Past interstitial lung disease, or (non-infectious) pneumonia and need oral or intravenous steroid therapy; 7) Long-term use of systemic hormones (dose equivalent to \>10mg prednisone/day) or any other form of immunosuppressive therapy is required. Subjects using inhaled or topical corticosteroids can be selected; 8) Active infections that require systemic treatment; 9) Human immunodeficiency virus (HIV, HIV1/2 antibody) positive; 10) A history of psychotropic drug abuse, alcohol or drug abuse; 11) Significant clinically significant bleeding symptoms or a clear tendency to appear within 3 months before enrollment; 12) Suspected of being allergic to study drugs; 13) Suffer from hypertension, and cannot be well controlled by antihypertensive medication (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg); 14) After antiviral therapy, HBvDNA\>104 copies/ml, HCV RNA\>1000; 15) Accompanied by ascites, hepatic encephalopathy, Gilbert syndrome, sclerosing cholangitis, etc. Combined with insufficiency of other organs, it is expected that they cannot accept general anesthesia or hepatectomy; 16) Other factors judged by the investigator that may affect the safety of the subject or the compliance of the trial. Such as serious illnesses (including mental illness) that require combined treatment, serious laboratory abnormalities, or other family or social factors.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine: collaborator
• Shanghai Public Health Clinical Center: collaborator
• RenJi Hospital: collaborator
• Shenzhen University General Hospital: collaborator
• Sir Run Run Shaw Hospital: collaborator
• Tang-Du Hospital: collaborator
• First Affiliated Hospital of Wenzhou Medical University: collaborator
• The First Affiliated Hospital of Zhengzhou University: collaborator
• The First Affiliated Hospital of Anhui Medical University: collaborator
• First Hospital of China Medical University: collaborator
• Eastern Hepatobiliary Surgery Hospital: collaborator
• First Affiliated Hospital Xi'an Jiaotong University: collaborator
• Shanghai Jiao Tong University Affiliated Sixth People's Hospital: collaborator
• First Affiliated Hospital of Guangxi Medical University: collaborator
• The Affiliated Hospital of Qingdao University: collaborator
• Peking Union Medical College Hospital: collaborator
• Meng Chao Hepatobiliary Hospital of Fujian Medical University: collaborator
• The First Affiliated Hospital of University of Science and Technology of China: collaborator
• Cancer Hospital of Guangxi Medical University: collaborator
• Tongji Hospital: collaborator
• Zhejiang Provincial People's Hospital: collaborator
• The Second Affiliated Hospital of Kunming Medical University: collaborator
• Sichuan Provincial People's Hospital: collaborator
• Taizhou Hospital: collaborator
• Shaoxing People's Hospital: collaborator
• The First Hospital of Hebei Medical University: collaborator

Study Sites (1)

Zhongshan hospital

Shanghai, Shanghai Municipality, 200032, China

Location

Related Publications (5)

• Shaib Y, El-Serag HB. The epidemiology of cholangiocarcinoma. Semin Liver Dis. 2004 May;24(2):115-25. doi: 10.1055/s-2004-828889.

  PMID: 15192785 BACKGROUND

• Shen WF, Zhong W, Xu F, Kan T, Geng L, Xie F, Sui CJ, Yang JM. Clinicopathological and prognostic analysis of 429 patients with intrahepatic cholangiocarcinoma. World J Gastroenterol. 2009 Dec 21;15(47):5976-82. doi: 10.3748/wjg.15.5976.

  PMID: 20014463 BACKGROUND

• Cho SY, Park SJ, Kim SH, Han SS, Kim YK, Lee KW, Lee SA, Hong EK, Lee WJ, Woo SM. Survival analysis of intrahepatic cholangiocarcinoma after resection. Ann Surg Oncol. 2010 Jul;17(7):1823-30. doi: 10.1245/s10434-010-0938-y. Epub 2010 Feb 18.

  PMID: 20165987 BACKGROUND

• Fisher SB, Patel SH, Kooby DA, Weber S, Bloomston M, Cho C, Hatzaras I, Schmidt C, Winslow E, Staley CA 3rd, Maithel SK. Lymphovascular and perineural invasion as selection criteria for adjuvant therapy in intrahepatic cholangiocarcinoma: a multi-institution analysis. HPB (Oxford). 2012 Aug;14(8):514-22. doi: 10.1111/j.1477-2574.2012.00489.x. Epub 2012 May 22.

  PMID: 22762399 BACKGROUND

• Yamashita Y, Taketomi A, Morita K, Fukuhara T, Ueda S, Sanefuji K, Iguchi T, Kayashima H, Sugimachi K, Maehara Y. The impact of surgical treatment and poor prognostic factors for patients with intrahepatic cholangiocarcinoma: retrospective analysis of 60 patients. Anticancer Res. 2008 Jul-Aug;28(4C):2353-9.

  PMID: 18751418 BACKGROUND

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Neoadjuvant Therapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Jia Fan, MD & PhD

  Shanghai Zhongshan Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2020
• First Posted: December 16, 2020
• Study Start: January 20, 2021
• Primary Completion: April 30, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 4, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)