A Phase III Trial of Intraarterial Therapies Plus Tislelizumab Plus Lenvatinib Versus Tislelizumab Plus Gemcitabine-Cisplatin in Unresectable Intrahepatic Cholangiocarcinoma (RAINBOW)

June 30, 2026 updated by: Gao-Jun Teng, Zhejiang Cancer Hospital

Transcatheter Arterial Chemoembolization in Combination With Tislelizumab Plus Lenvatinib Versus Systemic Cisplatin Plus Gemcitabine in Combination With Tislelizumab for Unresectable Intrahepatic Cholangiocarcinoma: A Phase III, Multicenter, Randomized Controlled Trial

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

140

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
      • Guangzhou, Guangdong, China, 510317
        • Guangdong Second People's Hospital
        • Contact:
      • Guangzhou, Guangdong, China, 510168
        • Jinshazhou Hospital of Guangzhou University of Chinese Medicine
        • Contact:
      • Guangzhou, Guangdong, China, 511400
        • The Affiliated Panyu Central Hospital of Guangzhou Medical University
        • Contact:
      • Guangzhou, Guangdong, China, 524003
        • The Second Affiliated Hospital of Guangdong Medical University
        • Contact:
      • Jiangmen, Guangdong, China, 529030
        • Jiangmen Central Hospital
        • Contact:
    • Hubei
      • Wuhan, Hubei, China, 430022
        • Wuhan Union Hospital of China
        • Contact:
    • Hunan
      • Changsha, Hunan, China, 410013
        • The Third Xiangya Hospital of Central South University
        • Contact:
      • Changsha, Hunan, China, 410011
        • The Second Xiangya Hospital Of Central South University
        • Contact:
    • Jiangxi
      • Ganzhou, Jiangxi, China, 341000
        • Ganzhou Hospital-Nanfang Hospital, Southern Medical University
        • Contact:
      • Nanchang, Jiangxi, China, 330209
        • The First Affiliated Hospital of Nanchang University
        • Contact:
    • Shandong
      • Qingdao, Shandong, China, 266000
        • The Affiliated Hospital of QingDao University
        • Contact:
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • West China School of Medicine/West China Hospital, Sichuan University (WCSM/WCH, SCU)
        • Contact:
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310022
        • Zhejiang Cancer Hospital
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Jiaping Zheng
      • Jinhua, Zhejiang, China, 321000
        • Jinhua Municipal Central Hospital
        • Contact:
      • Lishui, Zhejiang, China, 323020
      • Ningbo, Zhejiang, China, 315010
        • NingBo No.2 Hospital
        • Contact:
      • Ningbo, Zhejiang, China, 315048
        • Ningbo Medical Center Lihuili Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥18 years.
  2. Histologically confirmed intrahepatic cholangiocarcinoma that is unresectable or recurrent after curative treatment, without extrahepatic metastasis.
  3. No prior systemic therapy or transarterial interventional therapy for intrahepatic cholangiocarcinoma.
  4. At least one measurable intrahepatic lesion according to RECIST v1.1.
  5. ECOG performance status of 0 or 1.
  6. Child-Pugh class A liver function.
  7. Life expectancy ≥3 months.

  8. 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;
    • Serum creatinine <1.5 × upper limit of normal and creatinine clearance ≥60 mL/min.

Exclusion Criteria:

  1. Diffuse infiltrative liver lesions.
  2. Contraindications to TACE.
  3. Allergy to intravenous contrast agent.
  4. pregnant or breastfeeding women, or participants planning pregnancy within 2 years / unwilling to use effective contraception.
  5. Patients with HIV or syphilis infection.
  6. Patients with concurrent malignancies or other malignancies within 5 years before enrollment.
  7. History of allogeneic organ transplantation.
  8. Severe dysfunction of the heart, kidney, or other organs.
  9. Severe clinically active infection > grade 2 according to NCI-CTC v5.0.
  10. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TACE Plus Tislelizumab and Lenvatinib
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
Tislelizumab 200 mg intravenously on Day 1 of each 21-day cycle, followed by maintenance tislelizumab every 3 weeks.
Drug: Lenvatinib
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.
Procedure: Transcatheter Arterial Chemoembolization
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.
Procedure: Hepatic Arterial Infusion Chemotherapy
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.
Active Comparator: Gemcitabine-Cisplatin Plus Tislelizumab
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: Tislelizumab
Tislelizumab 200 mg intravenously on Day 1 of each 21-day cycle, followed by maintenance tislelizumab every 3 weeks.
Drug: Gemcitabine
Gemcitabine 1000 mg/m² intravenously on Days 1 and 8 of each 21-day cycle, up to 8 cycles.
Drug: Cisplatin
Cisplatin 25 mg/m² intravenously on Day 1 and Day 8 of each 21-day cycle, up to 8 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: From randomization to death from any cause, assessed up to approximately 48 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival
Time Frame: From randomization to disease progression or death, assessed up to approximately 48 months
Defined as the time from randomization to disease progression or death from any cause. Participants without progression or death will be censored at the last date known to be progression-free.
From randomization to disease progression or death, assessed up to approximately 48 months
Time to Progression
Time Frame: From randomization to disease progression, assessed up to approximately 48 months
Defined as the time from randomization to disease progression. Participants who die without prior progression, withdraw, are lost to follow-up, or remain progression-free at study end will be censored at the last date known to be progression-free.
From randomization to disease progression, assessed up to approximately 48 months
Objective Response Rate
Time Frame: Assessed every 6 weeks ±7 days, up to approximately 48 months
Defined as the proportion of participants achieving complete response or partial response according to RECIST v1.1.
Assessed every 6 weeks ±7 days, up to approximately 48 months
Disease Control Rate
Time Frame: Assessed every 6 weeks ±7 days, up to approximately 48 months
Defined as the proportion of participants achieving complete response, partial response, or stable disease according to RECIST v1.1.
Assessed every 6 weeks ±7 days, up to approximately 48 months
Incidence of Grade ≥3 Adverse Events
Time Frame: From first dose of study treatment through 28 days after the last dose of study treatment
Defined as the occurrence of grade 3 or higher hematologic or non-hematologic toxicities, graded according to CTCAE v5.0.
From first dose of study treatment through 28 days after the last dose of study treatment
Quality of Life Assessed by EORTC QLQ-C30
Time Frame: Baseline and during treatment/follow-up, assessed up to approximately 48 months
Quality of life will be assessed using the EORTC QLQ-C30 questionnaire.
Baseline and during treatment/follow-up, assessed up to approximately 48 months
Quality of Life Assessed by EQ-5D
Time Frame: Baseline and during treatment/follow-up, assessed up to approximately 48 months
Quality of life will be assessed using the EQ-5D questionnaire.
Baseline and during treatment/follow-up, assessed up to approximately 48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Zhejiang Cancer Hospital

Investigators

  • Principal Investigator: 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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

January 1, 2030

Study Completion (Estimated)

July 1, 2030

Study Registration Dates

First Submitted

June 30, 2026

First Submitted That Met QC Criteria

June 30, 2026

First Posted (Actual)

July 9, 2026

Study Record Updates

Last Update Posted (Actual)

July 9, 2026

Last Update Submitted That Met QC Criteria

June 30, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RAINBOW 01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared due to privacy, ethical, and regulatory considerations.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Intrahepatic Cholangiocarcinoma (Icc)

Clinical Trials on Tislelizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Australia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe