Intraarterial Therapies Plus Tislelizumab Plus Lenvatinib Versus Tislelizumab Plus Gemcitabine-Cisplatin in Unresectable Intrahepatic Cholangiocarcinoma

NCT07691515 | Not Yet Recruiting Phase 3

• 1 other identifier: RAINBOW 01
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 18

Brief Summary

This is a phase III, multicenter, open-label, randomized controlled trial designed to evaluate the efficacy and safety of arterially directed therapy in combination with tislelizumab plus lenvatinib compared with gemcitabine and cisplatin (GEMCIS) in combination with tislelizumab as first-line treatment for patients with unresectable intrahepatic cholangiocarcinoma. Approximately 140 eligible patients with histologically confirmed unresectable intrahepatic cholangiocarcinoma without extrahepatic metastasis will be enrolled and randomized in a 1:1 ratio to receive either TACE plus tislelizumab and lenvatinib or GEMCIS plus tislelizumab. In the TACE-based treatment arm, hepatic arterial infusion chemotherapy with gemcitabine and cisplatin may be administered during or after TACE at the investigator's discretion according to the protocol. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, time to progression, objective response rate, disease control rate, safety, and quality of life.

Conditions

Intrahepatic Cholangiocarcinoma (Icc)

Keywords

Intrahepatic Cholangiocarcinoma; randomized controlled trial; Transcatheter Arterial Chemoembolization; Tislelizumab; Lenvatinib; GemCis

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival is defined as the time from enrollment/randomization to death from any cause. Participants who withdraw are lost to follow-up or remain alive at the end of the study will be censored at the date they were last known to be alive.

  From randomization to death from any cause, assessed up to approximately 48 months

Secondary Outcomes (7)

• Progression-Free Survival

  From randomization to disease progression or death, assessed up to approximately 48 months

• Time to Progression

  From randomization to disease progression, assessed up to approximately 48 months

• Objective Response Rate

  Assessed every 6 weeks ±7 days, up to approximately 48 months

• Disease Control Rate

  Assessed every 6 weeks ±7 days, up to approximately 48 months

• Incidence of Grade ≥3 Adverse Events

  From first dose of study treatment through 28 days after the last dose of study treatment

Study Arms (2)

TACE Plus Tislelizumab and Lenvatinib

EXPERIMENTAL

Participants will receive tislelizumab 200 mg intravenously every 3 weeks and oral lenvatinib once daily at a starting dose of 12 mg for body weight ≥60 kg or 8 mg for body weight \<60 kg. TACE will be performed after initiation of lenvatinib and may be repeated based on radiologic response, residual viable tumor, liver function, and investigator assessment. Both conventional TACE (cTACE) and drug-eluting beads TACE are allowed, and hepatic artery infusion chemotherapy may be added at investigator's discretion. Treatment will continue until clinical progression, radiologic progressive disease according to RECIST v1.1, completion of 2 years of immunotherapy, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria.

Drug: Tislelizumab; Drug: Lenvatinib; Procedure: Transcatheter Arterial Chemoembolization; Procedure: Hepatic Arterial Infusion Chemotherapy

Gemcitabine-Cisplatin Plus Tislelizumab

ACTIVE COMPARATOR

Participants will receive cisplatin 25 mg/m² on Day 1 and Day 8, gemcitabine 1000 mg/m² on Days 1 and 8, and tislelizumab 200 mg on Day 1 of each 3-week cycle for up to 8 cycles. After completion of gemcitabine-cisplatin treatment, participants will continue tislelizumab 200 mg intravenously every 3 weeks. Treatment will continue until clinical progression, radiologic progressive disease according to RECIST v1.1, completion of 2 years of immunotherapy, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria.

Drug: Gemcitabine; Drug: Cisplatin; Drug: Tislelizumab

Interventions

Gemcitabine DRUG

Gemcitabine 1000 mg/m² intravenously on Days 1 and 8 of each 21-day cycle, up to 8 cycles.

Gemcitabine-Cisplatin Plus Tislelizumab

Cisplatin DRUG

Cisplatin 25 mg/m² intravenously on Day 1 and Day 8 of each 21-day cycle, up to 8 cycles.

Gemcitabine-Cisplatin Plus Tislelizumab

Tislelizumab DRUG

Tislelizumab 200 mg intravenously on Day 1 of each 21-day cycle, followed by maintenance tislelizumab every 3 weeks.

Gemcitabine-Cisplatin Plus Tislelizumab; TACE Plus Tislelizumab and Lenvatinib

Lenvatinib DRUG

Oral lenvatinib once daily, 12 mg for participants with body weight ≥60 kg or 8 mg for participants with body weight \<60 kg, with dose modification according to toxicity.

TACE Plus Tislelizumab and Lenvatinib

Transcatheter Arterial Chemoembolization PROCEDURE

Conventional TACE or drug-eluting bead TACE are allowed. TACE may be repeated based on imaging assessment every 6 weeks ±7 days and investigator judgment.

TACE Plus Tislelizumab and Lenvatinib

Hepatic Arterial Infusion Chemotherapy PROCEDURE

Optional hepatic arterial infusion chemotherapy with gemcitabine and cisplatin may be administered during or after TACE at the investigator's discretion according to protocol-defined dose ranges.

TACE Plus Tislelizumab and Lenvatinib

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• Histologically confirmed intrahepatic cholangiocarcinoma that is unresectable or recurrent after curative treatment, without extrahepatic metastasis.
• No prior systemic therapy or transarterial interventional therapy for intrahepatic cholangiocarcinoma.
• At least one measurable intrahepatic lesion according to RECIST v1.1.
• ECOG performance status of 0 or 1.
• Child-Pugh class A liver function.
• Life expectancy ≥3 months.
• Adequate hematologic, hepatic, renal, and thyroid function within 14 days before study start, defined as:
• Absolute neutrophil count ≥1.5 × 10⁹/L;
• Platelet count ≥75 × 10⁹/L;
• Hemoglobin ≥90 g/L;
• Serum albumin ≥30 g/L;
• Total bilirubin ≤1.5 × upper limit of normal;
• AST and ALT \<1.5 × upper limit of normal, and ALP \<4 × upper limit of normal;
• TSH \<1 × upper limit of normal, with T3 and T4 within the normal range;

You may not qualify if:

• Diffuse infiltrative liver lesions.
• Contraindications to TACE.
• Allergy to intravenous contrast agent.
• pregnant or breastfeeding women, or participants planning pregnancy within 2 years / unwilling to use effective contraception.
• Patients with HIV or syphilis infection.
• Patients with concurrent malignancies or other malignancies within 5 years before enrollment.
• History of allogeneic organ transplantation.
• Severe dysfunction of the heart, kidney, or other organs.
• Severe clinically active infection \> grade 2 according to NCI-CTC v5.0.
• Psychiatric illness that may affect the informed consent process; Inability to take oral medications; Participation in another drug clinical trial within 12 months before enrollment.

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (18)

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510060, China

Location

Jinshazhou Hospital of Guangzhou University of Chinese Medicine

Guangzhou, Guangdong, 510168, China

Location

Guangdong Second People's Hospital

Guangzhou, Guangdong, 510317, China

Location

The Affiliated Panyu Central Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 511400, China

Location

The Second Affiliated Hospital of Guangdong Medical University

Guangzhou, Guangdong, 524003, China

Location

Jiangmen Central Hospital

Jiangmen, Guangdong, 529030, China

Location

Wuhan Union Hospital of China

Wuhan, Hubei, 430022, China

Location

The Second Xiangya Hospital of Central South University

Changsha, Hunan, 410011, China

Location

The Third Xiangya Hospital of Central South University

Changsha, Hunan, 410013, China

Location

Ganzhou Hospital-Nanfang Hospital, Southern Medical University

Ganzhou, Jiangxi, 341000, China

Location

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330209, China

Location

The Affiliated Hospital of QingDao University

Qingdao, Shandong, 266000, China

Location

West China School of Medicine/West China Hospital, Sichuan University (WCSM/WCH, SCU)

Chengdu, Sichuan, 610041, China

Location

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, 310022, China

Location

Jinhua Municipal Central Hospital

Jinhua, Zhejiang, 321000, China

Location

Lishui Central Hospital

Lishui, Zhejiang, 323020, China

Location

NingBo No.2 Hospital

Ningbo, Zhejiang, 315010, China

Location

NingBo Medical Center Lihuili Hospital

Ningbo, Zhejiang, 315048, China

Location

MeSH Terms

Conditions

Cholangiocarcinoma; Cirrhosis, Familial, with Pulmonary Hypertension

Interventions

Gemcitabine; Cisplatin; tislelizumab; lenvatinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Gaojun Teng, MD

  Zhejiang Cancer Hospital

  PRINCIPAL INVESTIGATOR

• Min Kuang, MD

  First Affiliated Hospital, Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

• Jiansong Ji, MD

  The Central Hospital of Lishui City

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gaojun Teng, MD

CONTACT

+86 13805171500; gjteng@seu.edu.cn

Binyan Zhong, MD

CONTACT

+86 15850522044; byzhongir@sina.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Interventional Oncology Center

Study Record Dates

• First Submitted: June 30, 2026
• First Posted: July 9, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): July 1, 2030
• Last Updated: July 14, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (18)