## Protocol Section
### Identification Module
**NCT ID:** NCT04170179

**Brief Title:** Systemic Chemotherapy Plus Lenvatinib and Toripalimab for HCC With Extrahepatic Metastasis

**Official Title:** Systemic Chemotherapy of Oxaliplatin, Leucovorin, 5-fluorouracil Plus Lenvatinib and Toripalimab for Hepatocellular Carcinoma With Extrahepatic Metastasis: a Prospective, Single-arm Trial

#### Organization Study ID Info
**ID:** HCC-S068
#### Organization
**Class:** OTHER
**Full Name:** Sun Yat-sen University
### Status Module
#### Completion Date
**Date:** 2021-04-01

**Type:** ESTIMATED

#### Expanded Access Info
**Last Known Status:** RECRUITING
#### Last Update Post Date
**Date:** 2021-02-23

**Type:** ACTUAL

**Last Update Submit Date:** 2021-02-19

**Overall Status:** UNKNOWN

#### Primary Completion Date
**Date:** 2021-04-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2019-11-19

**Type:** ACTUAL

**Status Verified Date:** 2021-02

#### Study First Post Date
**Date:** 2019-11-20
**Type:** ACTUAL
**Study First Submit Date:** 2019-11-18
**Study First Submit QC Date:** 2019-11-18
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Sun Yat-sen University

#### Responsible Party

**Investigator Affiliation:** Sun Yat-sen University

**Investigator Full Name:** Shi Ming

**Investigator Title:** Proffessor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The purpose of this study is to evaluate the efficacy and safety of Systemic chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin plus lenvatinib and toripalimab in patients with hepatocellular carcinoma with extrahepatic metastasis

**Detailed Description:** Systemic chemotherapy of oxaliplatin, 5-fluorouracil and leucovorin was effective and safe for advanced hepatocellular carcinoma. Lenvatinib was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma, and programmed cell death protein-1 (PD-1) antibody was effective and tolerable in patients with advanced hepatocellular carcinoma. No study has evaluated systemic chemotherapyplus lenvatinib and toripalimab. Thus, the investigators carried out this prospective, single-arm study to find out it.

### Conditions Module

**Conditions:**

- Hepatocellular Carcinoma

**Keywords:**

- Hepatocellular Carcinoma

- Lenvatinib

- Toripalimab

- Systemic chemotherapy

- Oxaliplatin, leucovorin, 5-fluorouracil

- Extrahepatic metastasis

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 25

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Systemic chemotherapy of oxaliplatin , fluorouracil, and leucovorin every 3 weeks. Lenvatinib 12 mg (or 8 mg) once daily (QD) oral dosing. Toripalimab 240mg intravenously every 3 weeks.

**Intervention Names:**

- Procedure: Systemic chemotherapy

- Drug: Lenvatinib

- Drug: Toripalimab

**Label:** Systemic chemotherapy plus lenvatinib and toripalimab

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Systemic chemotherapy plus lenvatinib and toripalimab

**Description:** administration of oxaliplatin , fluorouracil, and leucovorin via the peripherally inserted central catheter every 3 weeks

**Name:** Systemic chemotherapy

**Type:** PROCEDURE

#### Intervention 2

**Arm Group Labels:**

- Systemic chemotherapy plus lenvatinib and toripalimab

**Description:** 12 mg (or 8 mg) once daily (QD) oral dosing.

**Name:** Lenvatinib

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Systemic chemotherapy plus lenvatinib and toripalimab

**Description:** 240mg intravenously every 3 weeks

**Name:** Toripalimab

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Progression was defined as progressive disease by independent radiologic review according to mRECIST or death from any cause

**Measure:** Progression free survival rate at 6 months

**Time Frame:** 6 months

#### Secondary Outcomes

**Description:** OS is the length of time from the date of randomization until death from any cause.

**Measure:** Overall survival (OS)

**Time Frame:** 6 months

**Description:** PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression or death due to any cause.

**Measure:** Progression free survival (PFS)

**Time Frame:** 6 months

**Description:** ORR, as determined based on tumor response according to mRECIST, is defined as the proportion of all randomized subjects whose best overall response (BOR) is either a CR or PR.

**Measure:** Objective response rate (ORR)

**Time Frame:** 6 months

**Description:** Safety will be evaluated according to the NCI CTCAE Version 4.03. All observations pertinent to the safety of the study medication will be recorded on the CRF and included in the final report.

**Measure:** Adverse events

**Time Frame:** 6 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL)
* Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria.
* Barcelona clinic liver cancer-stage C
* Eastern Cooperative Oncology Group performance status of 0 to 2
* With no previous treatment
* Presence of extrahepatic metastasis
* No Cirrhosis or cirrhotic status of Child-Pugh class A only
* Not amendable to surgical resection ,local ablative therapy and any other cured treatment.
* The following laboratory parameters:

Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/L Serum albumin ≥ 30 g/L ASL and AST ≤ 5 x upper limit of normal Serum creatinine ≤ 1.5 x upper limit of normal INR ≤ 1.5 or PT/APTT within normal limits Absolute neutrophil count (ANC) \>1,500/mm3

Exclusion Criteria:

* Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
* Known history of HIV
* History of organ allograft
* History of immunotherapy
* Known or suspected allergy to the investigational agents or any agent given in association with this trial.
* Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
* Evidence of bleeding diathesis.
* Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
* Known central nervous system tumors including metastatic brain disease

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** shiming@sysucc.org.cn

**Name:** Ming Shi, MD

**Phone:** +862087343938

**Role:** CONTACT

**Contact 2:**

**Email:** liqj@sysucc.org.cn

**Name:** QiJiong Li, MD

**Phone:** +862087343938

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Guangzhou

**Contacts:**

***Contact 1:***

- **Email:** shiming@mail.sysu.edu.cn

- **Name:** Ming Shi, MD

- **Phone:** 8620-87343115

- **Role:** CONTACT

**Country:** China

**Facility:** Cancer Center Sun Yat-sen University

**State:** Guangdong

**Status:** RECRUITING

**Zip:** 510060

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000009385

- Term: Neoplastic Processes

- ID: D000010335

- Term: Pathologic Processes

- ID: D000000230

- Term: Adenocarcinoma

- ID: D000008113

- Term: Liver Neoplasms

- ID: D000004067

- Term: Digestive System Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000008107

- Term: Liver Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M5534

- Name: Carcinoma

- Relevance: HIGH

- As Found: Carcinoma

- ID: M9613

- Name: Carcinoma, Hepatocellular

- Relevance: HIGH

- As Found: Hepatocellular Carcinoma

- ID: M12307

- Name: Neoplasm Metastasis

- Relevance: HIGH

- As Found: Metastases

- 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: M12330

- Name: Neoplastic Processes

- Relevance: LOW

- As Found: Unknown

- ID: M3585

- Name: Adenocarcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M11113

- Name: Liver Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8886

- Name: Gastrointestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7256

- Name: Digestive System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11107

- Name: Liver Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000002277

- Term: Carcinoma

- ID: D000009362

- Term: Neoplasm Metastasis

- ID: D000006528

- Term: Carcinoma, Hepatocellular

### Intervention Browse Module - Ancestors

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000047428

- Term: Protein Kinase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: ANeo

- Name: Antineoplastic Agents

### Intervention Browse Module - Browse Leaves

- ID: M6191

- Name: Leucovorin

- Relevance: LOW

- As Found: Unknown

- ID: M8600

- Name: Fluorouracil

- Relevance: LOW

- As Found: Unknown

- ID: M353738

- Name: Lenvatinib

- Relevance: HIGH

- As Found: Fibrillation

- ID: M1674

- Name: Oxaliplatin

- 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: C000531958

- Term: Lenvatinib

### Misc Info Module

- Version Holder: 2024-05-24
