Bile Duct Carcinoma, Cholangiocarcinoma
Conditions
Brief summary
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.
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.
Interventions
DRUGFGFR Inhibitor
FGFR Inhibitor
DRUGIDH1 mutation inhibitor
IDH1 mutation inhibitor
DRUGKRAS mutation inhibitor
KRAS mutation inhibitor
DRUGNTRK mutation inhibitor
NTRK mutation inhibitor
DRUGBRAF V600E mutation inhibitor
BRAF V600E mutation inhibitor
DRUGBRCA 1/2 mutation inhibitor
BRCA 1/2 mutation inhibitor
DRUGHER2 target therapy
HER2 target therapy
DRUGImmune Checkpoint Inhibitors
Immune Checkpoint Inhibitors
DEVICEChemotherapy: GP/GEMOX
Chemotherapy: GP/GEMOX
Sponsors
Zhejiang University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From enrollment to upto 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From enrollment to upto 2 years | Progression-Free Survival (PFS), defined as the time from randomization to the first documented disease progression or death from any cause, whichever occurs first. |
| Overall Survival (OS) | From enrollment to upto 3 years | Overall Survival (OS), defined as the time from randomization to death from any cause. |
| Disease Control Rate (DCR) | From enrollment to upto 2 years | 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. |
Countries
China
Contacts
CONTACTTingbo Liang, MD
CONTACTYiwen Chen, MD
Outcome results
None listed