## Protocol Section
### Identification Module
**NCT ID:** NCT06417606

**Brief Title:** Lenvatinib and Adebrelimab Combined With GEMOX in the Perioperative Treatment of Potentially Resectable Intrahepatic Cholangiocarcinoma

**Official Title:** A Single-arm, Prospective Clinical Study of Lenvatinib and Adebrelimab Combined With GEMOX in the Perioperative Treatment of Potentially Resectable Intrahepatic Cholangiocarcinoma

#### Organization Study ID Info
**ID:** IEC-ZN-01-AF 09
#### Organization
**Class:** OTHER
**Full Name:** Tongji Hospital
### Status Module
#### Completion Date
**Date:** 2025-05-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-22

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-21

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-04-20

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-30

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-07
**Study First Submit QC Date:** 2024-05-11
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Zhiyong Huang

#### Responsible Party

**Investigator Affiliation:** Tongji Hospital

**Investigator Full Name:** Zhiyong Huang

**Investigator Title:** Professor

**Type:** SPONSOR_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** A single-arm, prospective clinical study was conducted to enroll 20 subjects. Each subject was treated with oral Lenvatinib + Adebrelimab + GEMOX (gemcitabine + oxaliplatin). The treatment phase before surgery was 3 cycles, and the evaluation was performed every 2 cycles. The evaluation was repeated before surgery, and the decision of surgery was made according to the evaluation results.

To evaluate the efficacy and safety of Lenvatinib and Adebrelimab combined with GEMOX in the perioperative treatment of potentially resectable intrahepatic cholangiocarcinoma.

### Conditions Module

**Conditions:**

- Intrahepatic Cholangiocarcinoma

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 20

**Type:** ESTIMATED

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Lenvatinib（oral，12mg once daily if body weight ≥60Kg; Body weight \< 60Kg, 8mg/ day）； Adebrelimab（intravenous drip，1200mg once every 3 weeks）； GEMOX（intravenous drip，Gemcitabine 1000mg/m2, 2 times every 3 weeks d1+d8; intravenous drip，Oxaliplatin, 100mg/m2, was given every 3 weeks）

**Intervention Names:**

- Drug: Lenvatinib

**Label:** Lenvatinib and Adebrelimab Combined With GEMOX（Gemcitabine and oxaliplatin）

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Lenvatinib and Adebrelimab Combined With GEMOX（Gemcitabine and oxaliplatin）

**Description:** Lenvatinib（oral，12mg once daily if body weight ≥60Kg; Body weight \< 60Kg, 8mg/ day）； Adebrelimab（intravenous drip，1200mg once every 3 weeks）； GEMOX（intravenous drip，Gemcitabine 1000mg/m2, 2 times every 3 weeks d1+d8; intravenous drip，Oxaliplatin, 100mg/m2, was given every 3 weeks）

**Name:** Lenvatinib

**Other Names:**

- Adebrelimab

- GEMOX（Gemcitabine and oxaliplatin）

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Objective Response Rate

**Measure:** ORR

**Time Frame:** through study completion, an average of 1 year

**Description:** Disease Free Survival

**Measure:** DFS

**Time Frame:** through study completion, an average of 1 year

#### Secondary Outcomes

**Description:** The tumor was completely removed with negative margins, meaning no residual tumor

**Measure:** R0 resection rate

**Time Frame:** 1 year

**Description:** Overall Survival

**Measure:** OS

**Time Frame:** Up to 24 months

**Description:** Disease Control Rate

**Measure:** DCR

**Time Frame:** DCR will be calculated as the percentage of patients who achieved Stable Disease(SD) or better for more than 8 weeks (RECIST v1.1)

**Description:** Event Free Survival

**Measure:** EFS

**Time Frame:** Up to 12/24 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Voluntarily participated in this study, signed informed consent, aged 18-80 years
* Patients with locally advanced intrahepatic cholangiocarcinoma: (meet at least one of the following) A, the number of intrahepatic tumors was 2-3 B, the intrahepatic tumor is single but \>5cm in diameter C, the tumor was close to the 1/2 grade branch of the hepatic pedicle, making RO resection difficult D. Lymph node metastasis: MRI or PET/CT suggested regional lymph node metastasis
* The WHO/ECOG PS score was 0-1
* Imaging examination (CT/MRI/PET-CT) showed no distant metastasis
* Child-Pugh grade: A (≤6 points)
* Expected survival time ≥6 months
* No previous systemic treatment for hepatocellular carcinoma, including chemotherapy, targeted therapy, immunotherapy, etc. Patients who had undergone previous curative surgery or curative ablation were allowed, except those who had a recurrence within 2 years after curative surgery and those who had received other previous local treatment
* If you have hepatitis B virus (HBV) infection, such as HBsAg positive, you need to test HBV-DNA, and HBV-DNA should be less than 500IU/mL (; Patients with HBV-DNA of more than 500 IU per milliliter received antiviral therapy (only nucleoside agents such as entecavir, tenofovir dipivoxil fumarate, and tenofovir propofol fumarate tablets) for at least 1 week before randomization and had a decrease in viral copy number by a factor of more than 10. For patients with HBV infection, antiviral therapy should be received throughout the study period. Patients who are positive for hepatitis C virus (HCV) -RNA must receive antiviral therapy according to treatment guidelines
* Organs and bone marrow are sufficiently functional, defined as follows:

  1. hemoglobin ≥9g/dL
  2. absolute neutrophil count ≥1.5 × 109/L
  3. platelet count ≥ 100 × 109/L
  4. serum bilirubin ≤2.0× upper limit of normal (ULN); This condition does not apply to patients with proven Gilbert's syndrome. Any clinically significant biliary obstruction had to be relieved prior to enrollment in the study.
  5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be ≤2.5×ULN. For patients with liver metastases, ALT and AST should be ≤5 × ULN.

Exclusion Criteria:

* The investigator deemed the subject unfit to participate in the study
* Have active autoimmune disease or a history of autoimmune disease with possible recurrence (including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism)
* Use of immunosuppressant or systemic hormone therapy to achieve immunosuppression within 2 weeks before treatment (dose \>10mg/ day of prednisone or other effective hormones)
* patients with active infection, unexplained fever ≥38.5℃ within 1 week before randomization, or white blood cell count \>15×109/L during screening; Therapeutic antibiotics, administered orally or intravenously, were given within 2 weeks before randomization
* Patients with innate or acquired immune deficiency (e.g., HIV infection)
* History of other primary malignancies, with the exception of malignancies treated with curative treatment, known absence of active disease ≥5 years before the first study intervention, and low potential risk of recurrence; Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or lentigo maligna that has received potentially curative treatment; Or carcinoma in situ that has been adequately treated without evidence of disease
* Patients with clinically significant bleeding symptoms or a clear bleeding tendency within 6 months before treatment, such as gastrointestinal bleeding, severe esophagogastric varices, hemorrhagic gastric ulcer, or angiitis, can be reexamined if fecal occult blood is positive at baseline, and if it is still positive after reexamination, gastroscopy is required
* Known inherited or acquired bleeding (e.g. coagulopathy) or thrombophilia, such as in patients with hemophilia, coagulation disorders, thrombocytopenia, etc.; Currently receiving full-dose oral or injectable anticoagulants or thrombolytic agents for therapeutic purposes (prophylactic use such as low-dose aspirin is allowed)
* Known allergies to any study drug or excipients
* Participate in other drug clinical trials within 4 weeks before randomization
* Pregnant or lactating women
* Other factors considered by the investigator to be unsuitable for participation in the study

**Maximum Age:** 80 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** zunyizhangtjmu@163.com

**Name:** Zunyi Zhang

**Phone:** 86-15827413728

**Role:** CONTACT

**Contact 2:**

**Email:** d202382316@hust.edu.cn

**Name:** Guan Tan

**Phone:** 86-15971812255

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Wuhan

**Contacts:**

***Contact 1:***

- **Email:** zunyizhangtjmu@163.com

- **Name:** Zunyi Zhang

- **Phone:** 86-15827413728

- **Role:** CONTACT

***Contact 2:***

- **Email:** d202382316@hust.edu.cn

- **Name:** Guan Tan

- **Phone:** 86-15971812255

- **Role:** CONTACT

**Country:** China

**Facility:** Tongji Hospital

#### Overall Officials

**Official 1:**

**Affiliation:** Tongji Hospital

**Name:** Zhiyong Huang

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000000230

- Term: Adenocarcinoma

- ID: D000002277

- Term: Carcinoma

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M20426

- Name: Cholangiocarcinoma

- Relevance: HIGH

- As Found: Intrahepatic Cholangiocarcinoma

- ID: M3585

- Name: Adenocarcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: T755

- Name: Bile Duct Cancer

- Relevance: HIGH

- As Found: Cholangiocarcinoma

- ID: T3096

- Name: Intrahepatic Cholangiocarcinoma

- Relevance: HIGH

- As Found: Intrahepatic Cholangiocarcinoma

### Condition Browse Module - Meshes

- ID: D000018281

- Term: Cholangiocarcinoma

### Intervention Browse Module - Ancestors

- ID: D000000964

- Term: Antimetabolites, Antineoplastic

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000047428

- Term: Protein Kinase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M2985

- Name: Gemcitabine

- Relevance: HIGH

- As Found: Activity

- ID: M353738

- Name: Lenvatinib

- Relevance: HIGH

- As Found: Primary care

- ID: M1674

- Name: Oxaliplatin

- Relevance: HIGH

- As Found: Outcomes

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M25820

- Name: Protein Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000093542

- Term: Gemcitabine

- ID: D000077150

- Term: Oxaliplatin

- ID: C000531958

- Term: Lenvatinib

### Misc Info Module

- Version Holder: 2024-05-31
