Toripalimab Combined With Gemcitabine and Cisplatin (GemCis) as Preoperative Neoadjuvant Therapy for Resectable Intrahepatic Cholangiocarcinoma

Toripalimab Combined With Gemcitabine and Cisplatin (GemCis) as Preoperative Neoadjuvant Therapy for Resectable Intrahepatic Cholangiocarcinoma (ICC) With High Risk of Recurrence, Phase II, Single-center, Randomized Controlled Trial

This study was a randomized controlled trial to evaluate the efficacy and safety of toripalimab combined with GemCis (gemcitabine and cisplatin) as preoperative neoadjuvant therapy for resectable ICC at high risk of recurrence.

Study Overview

• Status: Recruiting
• Conditions: Intrahepatic Cholangiocarcinoma (Icc)
• Intervention / Treatment: Drug: Teripalimab; Drug: Gemcitabine + Cisplatin; Procedure: Surgery

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qiang Wu; Phone Number: +86-13821413914; Email: wuqiangtianjin@hotmail.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Institute and Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥ 18, male or female;

2. Pathological diagnosis confirmed intrahepatic cholangiocarcinoma, which could be resected surgically; One of the following conditions shall be met:

   2.1 Single tumor, diameter greater than 5cm (T1b) 2.2 Single tumor with vascular invasion (T2), multiple tumors ≤ 3 2.3 Tumor penetrating visceral peritoneum (T3) or directly invading surrounding organs (T4) 2.4 Suspicious lymph node metastasis in Zone 8, 12 or 13

3. Can not received systemic treatment before participating in the study;
4. ECOG PS score 0-1;
5. The main organs function normally, and there is no serious blood, heart, lung, liver, kidney, bone marrow and other functional abnormalities and immune deficiency diseases.

6. Laboratory inspection shall meet the following requirements:

   Women of childbearing age must have a negative pregnancy test (serum or urine) within 14 days before enrollment, and voluntarily use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug; For men, they should be surgically sterilized or agree to use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug.

7. The patient voluntarily participated and signed the informed consent form;
8. It is expected that the compliance is good, and the efficacy and adverse reactions can be followed up according to the requirements of the scheme.

Exclusion Criteria:

1. Patients who received PD-1, PD-L1, PD-L2, CTLA-4 before enrollment, or directly received another stimulatory or co inhibitory T cell receptor (such as CTLA-4, 0X40, CD137);
2. Any other research drugs within 4 weeks before enrollment;
3. Any active autoimmune disease or history of autoimmune disease (such as interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism after hormone replacement therapy);
4. Congenital or acquired immune function defects, such as human immunodeficiency virus (HIV) infection;
5. Uncontrollable clinical cardiac symptoms or diseases, such as NYHA II and above heart failure unstable angina pectoris, myocardial infarction within one year, and clinically significant supraventricular or ventricular arrhythmia requiring clinical intervention;
6. Severe infection (such as intravenous drip of antibiotics, antifungal or antiviral drugs) occurred within 4 weeks before the first drug administration, or fever of unknown cause>38.5 ° C occurred during screening/before the first drug administration;
7. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
8. Live attenuated vaccine shall be inoculated within 4 weeks before the first administration or planned during the study period;
9. Suffered from or accompanied by other system malignant tumors in the last 5 years (except cured skin basal cell carcinoma, cervical carcinoma in situ and ovarian cancer);
10. Allergic to any test drug;
11. Pregnant and lactating women, fertile subjects are unwilling to take effective contraceptive measures;
12. Uncontrollable psychosis;
13. Other situations that the researcher thinks are not suitable for inclusion. If the patient has central nervous system metastasis, has serious laboratory examination abnormalities, and is accompanied by family or social factors, it will affect the safety of the subject, or the collection of data and samples.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Control group	Procedure: Surgery; Radical resection
Experimental: Preoperative neoadjuvant therapy group	Drug: Teripalimab; 240mg intravenous injection, D1, q3w, for 9 weeks (3 cycles); Drug: Gemcitabine + Cisplatin; Gemcitabine 1000mg/m2 + cisplatin 25mg/m2, D1&D8, q3w, for 9 weeks (3 cycles); Procedure: Surgery; Radical resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
1-year recurrence-free survival rate	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
R0 resection rate	1 year
DCR	1 year
2-year OS	2-year
ORR	1 year
1-year OS	1 year
Occurrence of adverse reactions	1 year
30 day postoperative complication rate	1 year

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: December 3, 2024
• First Submitted That Met QC Criteria: December 3, 2024
• First Posted (Estimated): December 6, 2024

Study Record Updates

• Last Update Posted (Estimated): December 6, 2024
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: toripalimab; neoadjuvant therapy; Intrahepatic Cholangiocarcinoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Gemcitabine
• Other Study ID Numbers: E20241190

Drug and device information, study documents

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