Precision Integrated Strategies and Efficacy Evaluation for Biliary Tract Cancers: An Umbrella Platform Study

This study is a prospective, multicenter, open-label, umbrella phase II clinical trial. Based on different multigene expression profiling subtypes and potential molecular characteristics of various pathways, 8 treatment arms and 13 treatment groups are preliminarily designed. After successful screening, investigators will assign eligible subjects to a treatment group based on the patient's genetic test report (if available) and performance status. For subjects without a genetic test report, they will be allocated to Arm H to receive immunotherapy combined with chemotherapy or other regimens.

Study Overview

• Status: Not yet recruiting
• Conditions: Cholangiocarcinoma; Bile Duct Carcinoma
• Intervention / Treatment: Drug: FGFR Inhibitor; Device: Chemotherapy: GP/GEMOX; Drug: IDH1 mutation inhibitor; Drug: KRAS mutation inhibitor; Drug: NTRK mutation inhibitor; Drug: BRAF V600E mutation inhibitor; Drug: BRCA 1/2 mutation inhibitor; Drug: HER2 target therapy; Drug: Immune Checkpoint Inhibitors

Detailed Description

This study is a prospective, multicenter, open-label, umbrella phase II clinical trial. Based on different multigene expression profiling subtypes and potential molecular characteristics of various pathways, 8 treatment arms and 13 treatment groups are preliminarily designed. After successful screening, investigators will assign eligible subjects to a treatment group based on the patient's genetic test report (if available) and performance status. For subjects without a genetic test report, they will be allocated to Arm H to receive immunotherapy combined with chemotherapy or other regimens. The mutations involved include the following: A: FGFR, B: IDH1, C: KRAS, D: NTRK, E: BRAF V600E, F: BRCA1/2, G: HER2, and H: pan-negative. Additional corresponding targets may be added later based on clinical practice.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tingbo Liang, MD; Phone Number: 86+19941463683; Email: liangtingbo@zju.edu.cn
• Study Contact Backup: Name: Yiwen Chen, MD; Phone Number: 86+15088682641; Email: yiwenchen0705@126.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The First Affiliated Hospital of Zhejiang University School of Medicine
      • Contact: Yiwen Chen; Phone Number: 86+19941463683; Email: yiwenchen0705@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• The patient voluntarily joins this study and signs the informed consent form.
• Age: ≥18 years, male or female.
• Histologically or cytologically confirmed advanced biliary tract malignancies, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.
• No prior systemic therapy for advanced BTC (biliary tract cancer).
• At least one measurable lesion as per RECIST v1.1 (spiral CT scan long diameter ≥10 mm or short diameter of enlarged lymph node ≥15 mm; lesions previously treated with local therapy may be considered target lesions only after documented progression according to RECIST v1.1).
• ECOG performance status: 0-1.
• Expected survival ≥12 weeks.
• Adequate major organ function.
• Female subjects of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days before the first dose, must not be breastfeeding, and must voluntarily agree to use effective contraceptive measures during the study period and for 6 months after the last dose of chemotherapy. For male subjects with a female partner of childbearing potential, they must be surgically sterile or agree to use effective contraceptive measures during the study period and for 3 months after the last dose of chemotherapy; sperm donation is not allowed during the study.
• Subjects are expected to have good compliance and be able to follow the protocol requirements for efficacy and adverse event follow-up.

Exclusion Criteria:

• Has another active malignancy other than BTC within 5 years or concurrently.
• Has poorly controlled cardiac clinical symptoms or diseases.
• Has hypertension that cannot be reduced to normal range with antihypertensive medication; has a history of hypertensive crisis or hypertensive encephalopathy.
• Any clinically significant gastrointestinal disorders, including bleeding, inflammation, obstruction, or diarrhea > grade 2.
• Has experienced thrombotic or embolic events within 6 months before the start of study treatment.
• Use of strong CYP3A4/CYP2C19 inducers (including rifampin and its analogues, and St. John's Wort) or strong CYP3A4/CYP2C19 inhibitors and/or strong UGT1A inhibitors within 14 days prior to signing the informed consent form.
• Has uncontrolled infection at screening.
• Patients with congenital or acquired immunodeficiency.
• Has a history of brain metastases or has brain metastases.
• Women who are pregnant or plan to become pregnant during the study treatment period.
• Other patients deemed unsuitable for inclusion by the treating physician.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; patients with FGFR mutation. FGFR mutation inhibitor with GP/GEMOX.	Drug: FGFR Inhibitor; FGFR Inhibitor; Device: Chemotherapy: GP/GEMOX; Chemotherapy: GP/GEMOX
Experimental: Arm B; patients with IDH1 mutation. IDH1 mutation inhibitor with GP/GEMOX	Device: Chemotherapy: GP/GEMOX; Chemotherapy: GP/GEMOX; Drug: IDH1 mutation inhibitor; IDH1 mutation inhibitor
Experimental: Arm C; Patients with KRAS mutation. KRAS mutation inhibitor with GP/GEMOX	Device: Chemotherapy: GP/GEMOX; Chemotherapy: GP/GEMOX; Drug: KRAS mutation inhibitor; KRAS mutation inhibitor
Experimental: Arm D; Patients with NTRK mutation. NTRK mutation inhibitor with GP/GEMOX.	Device: Chemotherapy: GP/GEMOX; Chemotherapy: GP/GEMOX; Drug: NTRK mutation inhibitor; NTRK mutation inhibitor
Experimental: Arm E; Patients with BRAF V600E mutation. BRAF V600E mutation inhibitor with GP/GEMOX.	Device: Chemotherapy: GP/GEMOX; Chemotherapy: GP/GEMOX; Drug: BRAF V600E mutation inhibitor; BRAF V600E mutation inhibitor
Experimental: Arm F; Patients with BRCA 1/2 mutation. BRCA 1/2 mutation inhibitor with GP/GEMOX.	Device: Chemotherapy: GP/GEMOX; Chemotherapy: GP/GEMOX; Drug: BRCA 1/2 mutation inhibitor; BRCA 1/2 mutation inhibitor
Experimental: Arm G; Patients with HER2 positive. Trastuzumab rezetecan with GP/GEMOX.	Device: Chemotherapy: GP/GEMOX; Chemotherapy: GP/GEMOX; Drug: HER2 target therapy; HER2 target therapy
Experimental: Arm H; Patients without any known target. ICI with GP/GEMOX.	Device: Chemotherapy: GP/GEMOX; Chemotherapy: GP/GEMOX; Drug: Immune Checkpoint Inhibitors; Immune Checkpoint Inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate (ORR), defined as the proportion of subjects in the analysis population who have a confirmed complete response (CR) or partial response (PR) according to RECIST version 1.1.	From enrollment to upto 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Progression-Free Survival (PFS), defined as the time from randomization to the first documented disease progression or death from any cause, whichever occurs first.	From enrollment to upto 2 years
Overall Survival (OS)	Overall Survival (OS), defined as the time from randomization to death from any cause.	From enrollment to upto 3 years
Disease Control Rate (DCR)	Disease Control Rate (DCR), defined as the percentage of patients with confirmed complete response, partial response, or stable disease (≥ 8 weeks) among efficacy-evaluable patients.	From enrollment to upto 2 years

Collaborators and Investigators

• Sponsor: Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): August 10, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: July 20, 2026
• First Submitted That Met QC Criteria: July 27, 2026
• First Posted (Actual): July 28, 2026

Study Record Updates

• Last Update Posted (Actual): July 28, 2026
• Last Update Submitted That Met QC Criteria: July 27, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Biliary Tract Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Bile Duct Diseases; Biliary Tract Neoplasms; Cholangiocarcinoma; Bile Duct Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Immune Checkpoint Inhibitors
• Other Study ID Numbers: CAPT07

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