Intrahepatic Cholangiocarcinoma (Icc), Neoadjuvant Therapy
Conditions
Keywords
Intrahepatic cholangiocarcinom, neoadjuvant therapy
Brief summary
This is a multicenter, single-arm, exploratory clinical study for adults with locally advanced intrahepatic cholangiocarcinoma (ICC) that may be technically resectable but is difficult to remove directly by surgery. The study will evaluate whether perioperative treatment with Retlirafusp alfa, famitinib malate, and hepatic arterial infusion chemotherapy using gemcitabine and oxaliplatin (HAIC-GEMOX) can help control the tumor before surgery and support further treatment after surgery. Participants who meet the study requirements will receive neoadjuvant treatment before surgery. After surgery, participants will receive adjuvant treatment with Retlirafusp alfa combined with capecitabine or S-1. The study treatment and follow-up will continue until disease progression, unacceptable side effects, death, withdrawal of consent, or other protocol-defined stopping criteria. The main purpose of the study is to evaluate event-free survival. The study will also monitor tumor response, surgery-related outcomes, survival, and safety. Participants will have regular safety visits, blood tests, imaging examinations, and follow-up visits during and after treatment.
Interventions
DRUGRetlirafusp alfa
30 mg/kg, i.v., q3w, Day 3 of each 3-week cycle.
DRUGFamitinib malate
10 mg, orally, once daily.
hepatic arterial infusion, Day 1 of each 3-week cycle.
DRUGCapecitabine
1250 mg/m², orally twice daily, Days 1-14 of each 3-week cycle, as postoperative adjuvant therapy.
DRUGS-1
40 mg/m², orally twice daily, Days 1-28 of each 6-week cycle, as postoperative adjuvant therapy.
Hepatic arterial infusion chemotherapy with gemcitabine and oxaliplatin administered on Day 1 of each 3-week cycle.
Sponsors
The First Affiliated Hospital with Nanjing Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Participants must meet all of the following criteria: 1. Voluntarily agree to participate in the study and sign the informed consent form. 2. Age 18 to 75 years at the time of signing informed consent, male or female. 3. Histologically and/or cytologically confirmed intrahepatic cholangiocarcinoma. 4. ECOG performance status of 0 to 1. 5. No prior systemic therapy or tumor-related surgery, except biliary drainage. 6. No extrahepatic metastasis. 7. Considered technically resectable by an experienced hepatobiliary surgeon. 8. At least one measurable lesion according to RECIST 1.1. 9. Adequate organ and bone marrow function, as defined by the protocol. 10. Women of childbearing potential must have a negative serum pregnancy test within 7 days before treatment and agree to use effective contraception during the study and for 1 year after the last study treatment. Male participants with partners of childbearing potential must also agree to use effective contraception during the study and for 1 year after the last study treatment. 11. Life expectancy of at least 12 weeks.
Exclusion criteria
Participants meeting any of the following criteria will be excluded: 1. Pathological diagnosis of hepatocellular carcinoma, mixed liver cancer, or other non-cholangiocarcinoma malignant tumor components. 2. Prior systemic therapy or other tumor-related treatment, except biliary drainage. 3. Diagnosis of any other malignancy within 5 years before the first study treatment, except cured localized tumors such as cervical carcinoma in situ, basal cell carcinoma of the skin, or low-grade prostate cancer. 4. Known uncontrolled pulmonary fibrosis, interstitial lung disease, or acute lung disease. 5. Participation in another clinical trial of an investigational drug or device within 4 weeks before the first study treatment. 6. Active hepatitis B or hepatitis C infection. 7. Active autoimmune disease requiring systemic treatment within 2 years before the first
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival (EFS) | From the start of treatment until the first EFS event, assessed up to 36 months. | EFS is defined as the time from the start of treatment to the first occurrence of any event, including disease progression that precludes surgery, local or distant recurrence, or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response rate | At the time of surgical pathological assessment, assessed up to 36 months. | Percentage of participants who achieve pathological complete response after neoadjuvant treatment and surgery. |
| Major pathological response rate | At the time of surgical pathological assessment, assessed up to 36 months. | Percentage of participants who achieve major pathological response. Major pathological response is defined as residual viable tumor cells accounting for 50% or less of the tumor bed. |
| R0 resection rate | At the time of surgery, assessed up to 36 months. | Percentage of participants who undergo R0 resection, defined as no gross residual tumor and no tumor cells within 1 mm of the microscopic surgical margin. |
| Disease-free survival | From the date of surgery until recurrence or death, assessed up to 36 months. | DFS is defined as the time from the date of surgery to disease recurrence or death from any cause. |
| Overall survival | From the start of neoadjuvant treatment until death or last follow-up, assessed up to 36 months. | OS is defined as the time from the start of neoadjuvant treatment to death from any cause or the date of last follow-up. |
| Incidence and severity of adverse events | From the start of treatment through the safety follow-up period, assessed up to 36 months. | Safety will be assessed by the incidence and severity of adverse events and serious adverse events according to NCI-CTCAE v5.0, as well as changes in vital signs, laboratory test results, and quality-of-life scores. |
Countries
China
Contacts
CONTACTLu Ling Professor Lu, MD
CONTACTJianhua Rao Professor Rao, Ph.D.
STUDY_DIRECTORFeng Cheng, MD
The First Affiliated Hospital with Nanjing Medical University
Outcome results
None listed