PD-L1 Antibody Combined With CTLA-4 Antibody for Patients With Advanced Intrahepatic Cholangiocarcinoma Who Progressed After Standard Treatment

NCT04634058 | Active Not Recruiting Phase 2

• 1 other identifier: zs-ICC-PDCT
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to evaluate the efficacy and safety of PD-L1 antibody combined with the CTLA-4 antibody in patients with advanced ICC who progressed after standard treatment.

Conditions

Cholangiocarcinoma, Intrahepatic; PD-L1; CTLA4

Outcome Measures

Primary Outcomes (1)

• objective response rate (ORR)

  the objective response rate (ORR) of advanced ICC patients who progressed after standard treatment with PD-L1 antibody SHR-1316 combined with CTLA-4 antibody IBI310

  12 months

Secondary Outcomes (3)

• Safety: the potential side effects

  12 months

• overall survival

  18 months

• Progression free survival

  12 months

Study Arms (1)

PD-L1 antibody combined with CTLA-4 antibody

EXPERIMENTAL

After 4 cycles of PD-L1 antibody combined with CTLA-4 antibody treatment, PD-L1 monotherapy was maintained until the disease progressed or intolerable toxicity and adverse reactions or the medication was used for two years.

Drug: PD-L1 antibody combined with CTLA-4 antibody

Interventions

PD-L1 antibody combined with CTLA-4 antibody DRUG

After 4 cycles of PD-L1 monoclonal antibody combined with CTLA-4 monoclonal antibody treatment, PD-L1 monotherapy was maintained until the disease progressed or intolerable toxicity and adverse reactions or the medication was used for two years.

PD-L1 antibody combined with CTLA-4 antibody

Eligibility Criteria

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

You may qualify if:

• For unresectable or metastatic or postoperative recurrence, histologically confirmed advanced ICC, provide enough tissue samples for PD-L1, CTLA-4 immunohistochemistry, and exome sequencing
• The standard systemic treatment of advanced ICC (gemcitabine or platinum or fluorouracil) failed due to disease progression or toxicity
• There are measurable lesions defined by RECIST standard v1.1
• For patients with a history of liver chemoembolization, radiofrequency ablation/intervention, or radiotherapy, there must be measurable lesions outside the chemoembolization or radiotherapy area or measurable progression lesions at the chemoembolization or radiotherapy site
• ECOG physical strength status ≤ 1
• Life expectancy\> 3 months
• Adequate renal function: creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN) or glomerular filtration rate (GFR) ≥ 60mL/min/1.73 m2
• Sufficient liver function: bilirubin ≤ 1.5 × ULN and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN
• Sufficient bone marrow reserve: absolute value of neutrophils (ANC)\> 1500/mcl, platelets (Plts)\> 75,000/mcl, hemoglobin (Hgb) ≥ 9.0g/dl
• Prothrombin time/activated partial thromboplastin time (PT/PTT) \<1.5 × ULN
• Age ≥18 years old
• HBV infected persons must meet the following criteria to be eligible to participate in the study:
• Chronic hepatitis B virus (HBV) infection (defined as hepatitis B surface antigen \[HBsAg\] positive and/or detectable HBV DNA) subjects must have HBV viral load below 2000 IU/ml before the first dose of the study intervention. Active HBV-treated subjects with a viral load of less than 2000 IU/ml should receive antiviral therapy throughout the study intervention period and check the HBV viral load every 6 weeks. Subjects whose HBV infection is clinically cured (defined as HBsAg negative and anti-HBc positive) and whose HBV viral load cannot be detected during screening should be checked for HBV viral load every 6 weeks. If the viral load exceeds 2000 IU/ml, HBV treatment should be carried out. Antiviral treatment after completing the research intervention should follow local guidelines.
• The toxicity of the previous treatment has been restored to ≤1 grade (if there is surgery, the wound has completely healed)
• Female subjects of childbearing age must undergo a pregnancy test within 2 weeks before starting the study medication, and the result is negative, and are willing to use a medically approved high-efficiency contraceptive method during the study period and within 24 weeks after the last study drug administration (Such as intrauterine device, contraceptive pills or condoms); for male subjects whose partners are females of childbearing age, they should agree to use effective methods of contraception during the study period and within 24 weeks after the last study administration

You may not qualify if:

• Past treatment with CTLA-4 mAb
• Hilar cholangiocarcinoma or extrahepatic cholangiocarcinoma or periampullary carcinoma or gallbladder cancer
• Major surgery or radiotherapy within 4 weeks before enrollment
• Active, known, or suspected autoimmune diseases
• Congestive heart failure or symptomatic coronary artery disease within 3 months before enrollment
• Cerebrovascular accident occurred in the past 6 months
• Clinically significant bleeding, bleeding event, or thromboembolic disease occurred within 6 months
• History of bowel perforation
• A history of (non-infectious) pneumonia requiring steroid treatment or current pneumonia
• Known history of human immunodeficiency virus (HIV) infection
• History of severely impaired lung function or interstitial lung disease
• Diagnosed concurrent malignant tumors in the past 5 years (except for fully treated non-melanoma skin cancer, superficial transitional cell carcinoma of the bladder and cervical carcinoma in situ \[CIS\]) or any currently active malignant tumors
• HCV RNA positive test indicates the active period
• Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation
• Uncontrollable or symptomatic hypercalcemia

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Zhongshan hospital

Shanghai, 200032, China

Location

Related Publications (2)

• Lu JC, Zeng HY, Sun QM, Meng QN, Huang XY, Zhang PF, Yang X, Peng R, Gao C, Wei CY, Shen YH, Cai JB, Dong RZ, Shi YH, Sun HC, Shi YG, Zhou J, Fan J, Ke AW, Yang LX, Shi GM. Distinct PD-L1/PD1 Profiles and Clinical Implications in Intrahepatic Cholangiocarcinoma Patients with Different Risk Factors. Theranostics. 2019 Jul 9;9(16):4678-4687. doi: 10.7150/thno.36276. eCollection 2019.

  PMID: 31367249 BACKGROUND

• Lim YJ, Koh J, Kim K, Chie EK, Kim S, Lee KB, Jang JY, Kim SW, Oh DY, Bang YJ. Clinical Implications of Cytotoxic T Lymphocyte Antigen-4 Expression on Tumor Cells and Tumor-Infiltrating Lymphocytes in Extrahepatic Bile Duct Cancer Patients Undergoing Surgery Plus Adjuvant Chemoradiotherapy. Target Oncol. 2017 Apr;12(2):211-218. doi: 10.1007/s11523-016-0474-1.

  PMID: 28084572 BACKGROUND

MeSH Terms

Conditions

Cholangiocarcinoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Fan Jia, MD & PhD

  Shanghai Zhongshan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 17, 2020
• First Posted: November 18, 2020
• Study Start: March 26, 2021
• Primary Completion: September 30, 2023
• Study Completion: September 30, 2025
• Last Updated: April 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)