Combined Therapy Using D-TACE, Gemcitabine and Cisplatin, and PD1 Antibody in Advanced and Unresectable Intrahepatic Cholangiocarcinoma

Combined Therapy Using D-TACE, Gemcitabine and Cisplatin Chemotherapy, and PD1 Antibody for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma: a Single-center, Single-arm Trial

The goal of this clinical trial is to learn about the combined therapy using drug-eluting bead-transarterial chemoembolization (D-TACE), gemcitabine (Gem) and cisplatin (Cis) chemotherapy, and PD-1 antibody in patients with advanced and unresectable intrahepatic cholangiocarcinoma (ICC). The main questions it aims to answer are:

• Whether combined therapy using D-TACE, Gem/Cis, and PD-1 works well to convert unresectable ICC to resectable.
• Whether combined therapy using D-TACE, Gem/Cis, and PD-1 is safe. Participants will receive D-TACE (CalliSpheres with Gem 30 mg), camrelizumab (200 mg) plus gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2), and 24 months follow-up.

Study Overview

• Status: Recruiting
• Conditions: Unresectable Intrahepatic Cholangiocarcinoma
• Intervention / Treatment: Drug: Camrelizumab; Drug: Gemcitabine Injection; Drug: Cisplatin injection; Drug: Cisplatin-Eluting Beads; Procedure: D-TACE

• Study Type: Interventional
• Enrollment (Estimated): 22
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hua Li, MD&PhD; Phone Number: +8613060975202; Email: lihua100@yeah.net
• Study Contact Backup: Name: Linsen Ye, MD&PhD; Phone Number: +8618520788663; Email: ye_linsen@163.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • The Third Affiliated Hospital of Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years old, male or female;
2. Histopathologically confirmed intrahepatic cholangiocarcinoma;
3. Tumor is unresectable assessed by the expert group (R0 resection CANNOT be achieved) and the life expectancy is more than 3 months;
4. Presence of at least one measurable lesion assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST version 1.1);
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Child-Pugh score ≤ 7;
7. Adequate organ function (neutrophil count of ≥1.5×10^9 cells/L, hemoglobin concentrations of ≥90 g/L, platelet cell count of ≥100×10^9 cells/L, bilirubin ≤1.5×ULN, Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 5×ULN, serum creatinine ≤ 1.5 x ULN, Thyroid stimulating hormone (TSH) ≤ 1 x ULN;
8. The patient must be required to sign an informed consent form;

Exclusion Criteria:

1. Patients who have received previous treatment with interventional therapy, radiotherapy, ablation, chemotherapy, targeted therapy, immunotherapy (PD-1, PD-L1, CLTA-4 antibody, etc), or surgery within the last 2 months;
2. Patients with other malignant tumors within the last 5 years, except for cured non-melanoma skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma;
3. Active tuberculosis infection. Patients with active tuberculosis infection within 1 year prior to enrollment; had a history of active tuberculosis infection more than 1 year before enrollment, did not receive formal anti-tuberculosis treatment or tuberculosis is still active;
4. Active infection requiring systemic therapy;
5. Human immunodeficiency virus (HIV) positive;
6. Have an active, known, or suspected autoimmune disease. Subjects who require only hormone replacement therapy for hypothyroidism and skin diseases that do not require systemic therapy may be enrolled;
7. Suffering from high blood pressure, and can not be well controlled by antihypertensive drugs (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg);
8. Abnormal blood coagulation (INR >1.5, or PT>ULN+4s, or APTT >1.5 x ULN), with a bleeding tendency or receiving thrombolytic or anticoagulant therapy;
9. Pregnant or lactating women;
10. Participated in other trials within the last 4 weeks;
11. Has a history of allergy to platinum;
12. Other factors that may influence the safety of the subject or the compliance of the test by the investigator. Serious illnesses (including mental illness), severe laboratory tests, or other family or social factors that require combined treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combined Therapy Using D-TACE, Gemcitabine and Cisplatin, and Camrelizumab; D-TACE with cisplatin-eluting beads. More TACE can be done if clinically necessary. Camrelizumab (200 mg, Intravenous drips (ivd), D1/3W) plus Gem (1000 mg/m2, ivd, D1&8/3W) and Cis (25 mg/m2, ivd, D1&8/3W). Three weeks are one cycle of treatment. Chemotherapy lasted for no more than 12 cycles.

Drug: Camrelizumab; 200mg on day1 of every 3 weeks, starting on day1 of cycle1; Drug: Gemcitabine Injection; 1000mg/m2 on day1 & day8 of every 3 weeks, starting on day1 of cycle 1; Drug: Cisplatin injection; 25mg/m2 on day1 & day8 of every 3 weeks, starting on day1 of cycle 1; Drug: Cisplatin-Eluting Beads; used for D-TACE; Procedure: D-TACE; TACE with Cisplatin-Eluting Beads (with Cis 30mg). More TACE can be done if clinically necessary.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conversion rate	Rate of unresectable ICC convert to resectable in combination therapy	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Rate of participants with treatment-related adverse events as assessed by CTCAE v4.0	12 months
Objective Response Rate (ORR)	ORR according to RECIST 1.1 using investigator assessment	12 months
Deepness of response (DpR)	DpR according to RECIST 1.1 using investigator assessment	12 months
Disease control rate (DCR)	DCR according to RECIST 1.1 using investigator assessment	12 months
Rate of R0 resection	R0 resection is defined as no tumor remains at the cutting edge and no tumor cells remain at the cutting edge under the microscope	12 months
Overall Survival (OS)	OS is defined as the time from date of combined theray start to the date of death from any cause or to the date of last follow-up if patients are alive.	12 months
Progression-free Survival (PFS)	From the beginning date of combined therapy to the date of disease progression. PFS according to RECIST 1.1 using investigator assessment	12 months
Recurrence-free Survival (RFS)	RFS is defined as the time between the date of surgery and the date of disease recurrence or death, whichever occurred first. RFS according to RECIST 1.1 using investigator assessment	12 months

Collaborators and Investigators

• Sponsor: Hua Li
• Investigators: Study Chair: Yang Yang, MD&PhD, Third Affiliated Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2023
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: February 14, 2023
• First Submitted That Met QC Criteria: February 17, 2023
• First Posted (Actual): February 21, 2023

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 22, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Cisplatin; Gemcitabine
• Other Study ID Numbers: [2023]02-116-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No