Combining Chemoradiotherapy With Sintilimab in First-Line ICC

Chemoradiotherapy Combined With Slulimumab in the Treatment of First-line Intrahepatic Cholangiocarcinoma: Efficacy and Safety Evaluation of a Phase II Clinical Study

To evaluate the effectiveness and safety of GC (gemcitabine + cisplatin) and radiotherapy combined with slulimumab in the treatment of first-line intrahepatic cholangiocarcinoma patients

Study Overview

• Status: Not yet recruiting
• Conditions: ICC
• Intervention / Treatment: Radiation: radiotherapy; Drug: gemcitabine + cisplatin; Drug: slulimumab

• Study Type: Observational
• Enrollment (Estimated): 19

Contacts and Locations

• Study Contact: Name: Shisuo Du; Phone Number: +86 136 2183 0381; Email: du.shisuo@zs-hospital.sh.cn
• Study Contact Backup: Name: Shu-jung Hsu; Phone Number: +8613585805072; Email: 21111210002@m.fudan.edu.cn

Study Locations

• China
  • Shanghai, China, 200032
    • Zhongshan Hospital
    • Contact: Shisuo Du; Phone Number: +86 136 2183 0381; Email: du.shisuo@zs-hospital.sh.cn
    • Principal Investigator: Shisuo Du

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

First-line patients with intrahepatic cholangiocarcinoma

Description

Inclusion Criteria:

1. Cholangiocarcinoma confirmed by histology/cytology.
2. The included patients were patients with first-line intrahepatic cholangiocarcinoma treated with GC (gemcitabine + cisplatin) and radiotherapy combined with slulimumab. All lesions are required to be eligible for RT treatment, and at least one of them is evaluable.

3. Liver function Child-Pugh class A, other laboratory tests:

   Neutrophils ≥1.5×109/L； Platelets ≥75×109/L；Hemoglobin ≥90g/L (no blood transfusion record within 2 weeks or no dependence on erythropoietin (EPO))；Serum creatinine ≤1.5 times ULN or calculated creatinine clearance ≥ 60 ml/min (Cockcroft-Gault formula)；AST ≤2.5×ULN, ALT ≤2.5×ULN; if intrahepatic lesions are present, ALT and AST ≤5×ULN；TSH, FT3, FT4 within ± 10% of normal values；Coagulation function: international normalized ratio (INR) ≤ 2 times ULN, and activated partial thromboplastin time (APTT) ≤ 1.5 times ULN

4. ECOG score 0-1 points.
5. Expected survival time > 3 months.
6. No history of radiation therapy.
7. Age ≥18 years old and ≤75 years old.
8. Sign the informed consent form and be able to comply with the visits and related procedures stipulated in the plan.
9. Female subjects of childbearing age or male subjects whose sexual partners are women of childbearing age must take effective contraceptive measures during the entire treatment period and for 6 months after the treatment period.

Exclusion Criteria:

1. Histology includes components such as hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, and sarcomatoid hepatocellular carcinoma.
2. Have a history of hepatic encephalopathy or liver transplantation.
3. Pleural effusion, ascites, and pericardial effusion with clinical symptoms or needing drainage, only imaging shows a small amount of pleural effusion, ascites, and pericardial effusion and are asymptomatic and can be selected.
4. People with acute or chronic active hepatitis B or hepatitis C infection, hepatitis B virus (HBV) DNA>2000IU/ml or 104 copies/ml; hepatitis C virus (HCV) RNA>103 copies/ml; hepatitis B Surface antigen (HbsAg) and anti-HCV antibodies were positive at the same time.
5. Symptomatic central nervous system metastasis. Patients with asymptomatic brain metastases or stable symptoms after treatment of brain metastases can participate in this study as long as they meet all the following criteria: measurable lesions outside the central nervous system; no midbrain, pons, cerebellum, meninges, Bulbar or spinal cord metastases; maintain clinical stability for at least 4 weeks; discontinue glucocorticoid therapy two weeks before the first dose of study drug.
6. History of gastrointestinal perforation and/or fistula, intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), inflammatory bowel disease, or extensive intestinal resection (partial colectomy or extensive small bowel resection) within the past 6 months , complicated by chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.
7. History of interstitial pneumonia, drug-induced pneumonia, idiopathic pneumonia or active pneumonia. Radiation pneumonitis within the radiation treatment area is permitted.
8. Active tuberculosis (TB), currently receiving anti-tuberculosis treatment or those who have received anti-tuberculosis treatment within 1 year before the first dose.
9. People infected with human immunodeficiency virus (HIV) (HIV 1/2 antibody positive).
10. Severe infection in active stage or with poor clinical control. Severe infection within 4 weeks before first dose, including but not limited to hospitalization due to complications of infection, bacteremia, or severe pneumonia.
11. Active autoimmune diseases that require systemic treatment or a history of the disease within the past 2 years (vitiligo, psoriasis, alopecia or Grave's disease that does not require systemic treatment within the past 2 years, only thyroid hormone is required Patients with hypothyroidism requiring replacement therapy and patients with type I diabetes requiring only insulin replacement therapy are eligible). Known history of primary immunodeficiency. Patients who are only positive for autoimmune antibodies need to confirm whether there is an autoimmune disease according to the researcher's judgment.
12. Use of immunosuppressive drugs within the past 4 weeks, excluding topical glucocorticoids by nasal spray, inhalation or other routes or systemic glucocorticoids at physiological doses (i.e. not exceeding 10 mg/day of prednisone or other (other glucocorticoids at effective doses), and the temporary use of glucocorticoids for the treatment of dyspnea symptoms in diseases such as asthma and chronic obstructive pulmonary disease is allowed.
13. Have received live attenuated vaccines within the past 4 weeks or plan to during the study period.
14. Have received systemic immunostimulant treatment within the past 4 weeks.
15. Received major surgical surgery (craniotomy, thoracotomy or laparotomy) or unhealed wounds, ulcers or fractures within the past 4 weeks.
16. Uncontrolled metabolic disorders or other non-malignant tumor organs or systemic diseases or secondary reactions to cancer, which may lead to higher medical risks and/or uncertainty in survival evaluation.
17. Other acute or chronic diseases, psychiatric disorders, or abnormal laboratory test values that may increase the risks associated with study participation or administration of study drugs, or interfere with the interpretation of study results, and which, at the discretion of the investigator, may cause the patient to were listed as ineligible to participate in this study.
18. Other malignant tumors diagnosed within 5 years before the first dose, excluding radically cured cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and/or radically resected carcinoma in situ. If other malignant tumors or liver cancer are diagnosed more than 5 years before administration, pathological or cytological diagnosis of recurrent and metastatic lesions is required.
19. Pregnant or breastfeeding female patients.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
GC (gemcitabine + cisplatin) + radiotherapy + slulimumab Group; First-line treatment for patients with intrahepatic bile duct carcinoma involves the administration of GC (gemcitabine plus cisplatin) along with radiotherapy and sintilimab.	Radiation: radiotherapy; radiotherapy; Other Names: RT; Drug: gemcitabine + cisplatin; Gemcitabine 1000mg/m² intravenous infusion over 30 minutes, cisplatin 25mg/m² intravenous infusion, on day 1 and day 8, every 3 weeks.; Other Names: GC; Drug: slulimumab; Slulimumab, 4.5mg/kg intravenous infusion, Q3W; Other Names: HLX10

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival(PFS)	The time from the date of first treatment to disease progression or death, whichever occurs first.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-To-Progression	The time from the date of first treatment to any recorded imaging tumor progression.	2 years
Objective Response Rate	The use of RECIST version 1.1 standards to evaluate the objective efficacy of tumors, including cases of CR and PR.	2 years
Disease Control Rate	The percentage of CR, PR and SD (≥4 weeks) cases among patients whose efficacy can be evaluated.	2 years
Incidence of Adverse events	AEs and SAEs, drug-related AEs and SAEs.	2 years

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Investigators: Principal Investigator: Shisuo Du, Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 3, 2024
• First Submitted That Met QC Criteria: June 6, 2024
• First Posted (Actual): June 7, 2024

Study Record Updates

• Last Update Posted (Actual): June 7, 2024
• Last Update Submitted That Met QC Criteria: June 6, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Gemcitabine
• Other Study ID Numbers: zs-ICC-RT+GC+HLX10

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The IPD will not be shared with other researchers in order to protect patients' privacy.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No