## Protocol Section
### Identification Module
**NCT ID:** NCT06418659

**Brief Title:** A Clinical Trial Evaluating the Safety and Efficacy of Intravenous CD-801 in Treating Advanced HCC Patients

**Official Title:** A Clinical Trial Assessing the Safety and Efficacy of Intravenous CD-801 for the Treatment of Patients With Advanced Hepatocellular Carcinoma

#### Organization Study ID Info
**ID:** CZXH-HCC-2024-IIT
#### Organization
**Class:** OTHER
**Full Name:** Shanghai Changzheng Hospital
### Status Module
#### Completion Date
**Date:** 2026-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-17

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-16

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-04

**Type:** ESTIMATED

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

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-17
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-13
**Study First Submit QC Date:** 2024-05-16
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Shanghai Changzheng Hospital

#### Responsible Party

**Investigator Affiliation:** Shanghai Changzheng Hospital

**Investigator Full Name:** Wei-Fen Xie

**Investigator Title:** Director, Department of Gastroenterology, Changzheng Hospital

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The goal of this investigator-initiated, a single-arm, open-label, pilot study is to investigate the safety, tolerability, and efficacy of Intravenous CD-801 treatment in subjects with advanced hepatocellular carcinoma(HCC).

Condition of disease: advanced hepatocellular carcinoma.

Intervention： CD-801 will be administered intravenously for the treatment of HCC. The dosing regimen is planned for a second dose 14 ± 3 days post-initial treatment, followed by subsequent treatments every 28 ± 7 days, with adjustments made based on patient tolerance and therapeutic response. The trial is structured in two phases: dose escalation and dose expansion.

Dose Escalation Phase:

The study employs a i3+3 design to assess escalating CD-801 dosages: 25 μg, 50 μg, and 100 μg. Post-initial dose, a 14-day DLT observation will evaluate tolerability and safety, guiding dose adjustments or selection of the Recommended Dose (RD) for the expansion phase. Cohorts may include up to 9 participants, adjusted for safety.

Dose Expansion Phase:

The expansion phase will use the safe dosage and regimen from the escalation phase, with treatments starting 14 ± 3 days after the initial dose, then every 28 ± 7 days, adjusted as needed. It ends upon complete response, disease progression, toxicity, withdrawal, loss to follow-up, new oncological treatments, or investigator termination, with a final assessment 14 days post-last dose. The phase plans to enroll about 10 participants to further assess CD-801's safety, tolerability, and antitumor effects using mRECIST.

Drug: CD-801, a drug specifically designed to target liver cancer cells and facilitate the expression of HNF4α.

**Detailed Description:** Hepatocellular carcinoma (HCC) is the most common form of liver cancer. Recent advancements in understanding tumor biology and the tumor microenvironment, along with the approval of systemic therapeutic agents, including immunotherapy and vascular endothelial growth factor (VEGF)-targeted agents, have dramatically transformed the treatment landscape for advanced stage HCC. However, the survival for advanced HCC patients still remains unsatisfactory.

Differentiation therapy in oncology is defined as a therapeutic strategy that reactivates endogenous differentiation programs and reverts malignant phenotypes. Its hallmark success is the treatment of acute promyelocytic leukemia (APL) by the combination of all-trans retinoic acid (ATRA) and arsenic. Unfortunately, this approach has achieved limited success in solid tumors.

Hepatocyte nuclear factor 4α (HNF4α) is a transcription factor (TF) belonging to the nuclear receptor family. HNF4α is highly enriched in mature hepatocytes and serves as a master regulator of hepatocyte differentiation and hepatic metabolism. Previous studies, including our own and others, have demonstrated that the reduced expression of HNF4α plays a critical role in hepatocarcinogenesis. Restoring HNF4α expression induces the differentiation of HCC cells into mature hepatocytes and has shown significant therapeutic effects in various animal models of HCC.

In this study, we developed CD-801, a drug specifically designed to target liver cancer cells and facilitate the expression of HNF4α, for the treatment of HCC patients. Preclinical studies have shown that CD-801 effectively inhibits the growth of subcutaneous and orthotopic liver tumors in mice. Acute toxicity tests in Sprague-Dawley rats have demonstrated that a single intravenous injection of CD-801 injection at a dose of 150 μg/animal is well-tolerated, with no significant toxicity, indicating good safety profiles.

This trial, structured in two phases: dose escalation and dose expansion, is a single-arm, open-label, exploratory clinical study aimed at evaluating the efficacy, safety, and tolerability of CD-801 administered intravenously through a peripheral vein in the treatment of advanced-stage HCC. The treatment schedule is planned for a second dose 14 ± 3 days post-initial treatment, followed by subsequent treatments every 28 ± 7 days, with adjustments made based on patient tolerance and therapeutic response.

### Conditions Module

**Conditions:**

- Advanced Hepatocellular Carcinoma

**Keywords:**

- Hepatocellular carcinoma

- Hepatocyte nuclear factor 4α

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** The subjects with advanced HCC will be treated by CD-801 intravenously via a peripheral vein.

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 37

**Type:** ESTIMATED

**Phases:**

- EARLY_PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** The subjects with advanced HCC will be treated by CD-801 intravenously via a peripheral vein.

**Intervention Names:**

- Drug: CD-801

**Label:** CD-801 treatment

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- CD-801 treatment

**Description:** CD-801 will be administered intravenously for the treatment of HCC. The dosing regimen is planned for a second dose 14 ± 3 days post-initial treatment, followed by subsequent treatments every 28 ± 7 days, with adjustments made based on patient tolerance and therapeutic response.

**Name:** CD-801

**Type:** DRUG

### Outcomes Module

#### Other Outcomes

**Description:** To evaluate the impact of CD-801 treatment on Health Related Quality of Life for subjects treated using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30.

**Measure:** Health Related Quality of Life based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).

**Time Frame:** Through study completion, an average of 2 years

**Description:** To evaluate the impact of CD-801 treatment on Health Related Quality of Life for subjects treated using HCC-specific EORTC QLQ-HCC18 questionnaire.

**Measure:** Health Related Quality of Life based on HCC-specific EORTC QLQ-HCC18 questionnaire.

**Time Frame:** Through study completion, an average of 2 years

**Description:** To evaluate the impact of CD-801 treatment on Health Related Quality of Life for subjects treated using European Quality of Life questionnaire.

**Measure:** Health Related Quality of Life based on European Quality of Life questionnaire.

**Time Frame:** Through study completion, an average of 2 years

**Description:** To investigate the changes in serum tumor biomarkers among subjects with advanced HCC following CD-801 treatment.

**Measure:** The impact of CD-801 treatment on tumor biomarkers in serum.

**Time Frame:** Through study completion, an average of 2 years

**Description:** To investigate the changes in serum cytokines among subjects with advanced HCC following CD-801 treatment.

**Measure:** The impact of CD-801 treatment on cytokines in serum.

**Time Frame:** Through study completion, an average of 2 years

**Description:** To investigate the changes of immune cell profiling in serum among subjects with advanced HCC following CD-801 treatment.

**Measure:** The impact of CD-801 treatment on immune cell profiling in serum.

**Time Frame:** Through study completion, an average of 2 years

**Description:** To investigate the changes of histopathology in tumor tissue among subjects with advanced HCC following CD-801 treatment.

**Measure:** The impact of CD-801 treatment on tumor histopathology.

**Time Frame:** Through study completion, an average of 2 years

**Description:** To investigate the changes of tumor metabolism through metabolomic analysis of liver cancer tissue among subjects with advanced HCC following CD-801 treatment.

**Measure:** The impact of CD-801 treatment on tumor metabolism.

**Time Frame:** Through study completion, an average of 2 years

**Description:** To investigate the changes of tumor gene expression profiles through next-generation sequencing and single-cell sequencing analysis of liver cancer tissue among subjects with advanced HCC following CD-801 treatment.

**Measure:** The impact of CD-801 treatment on gene expression profiles within tumors.

**Time Frame:** Through study completion, an average of 2 years

#### Primary Outcomes

**Description:** Safety and tolerability are assessed based on the incidence of Dose-Limiting Toxicities (DLTs) within 14 days post-initial drug administration, along with the frequency and severity of adverse events (AEs), serious adverse events (SAEs), and events leading to treatment discontinuation throughout the treatment period, all evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

**Measure:** (Escalation part) To evaluate the tolerability and safety for intravenous CD-801 in subjects with hepatocellular carcinoma (HCC)

**Time Frame:** Through study completion, an average of 2 years

**Description:** To assess the proportion of subjects who have best overall response of complete response or partial response at the time of data cutoff based on mRECIST.

**Measure:** (Expansion part) To assess the objective response rate (ORR) by modified Response Evaluation Criteria in Solid Tumours (mRECIST).

**Time Frame:** From the first study dose date until the date of documented complete response or partial response, assessed up to 24 months

#### Secondary Outcomes

**Description:** To assess the proportion of subjects who have best overall response of complete response or partial response at the time of data cutoff based on mRECIST and RECIST v1.1.

**Measure:** (Escalation part) To assess the objective response rate (ORR) by mRECIST and RECIST v1.1.

**Time Frame:** From the first study dose date until the date of documented complete response or partial response, assessed up to 24 months.

**Description:** To assess the frequency and severity of AEs, SAEs, and events leading to treatment discontinuation throughout the treatment period, all evaluated using CTCAE 5.0.

**Measure:** (Expansion part) To evaluate the tolerability and safety for intravenous CD-801 in subjects with HCC

**Time Frame:** Through study completion, an average of 2 years

**Description:** To assess the proportion of subjects who have best overall response of complete response or partial response at the time of data cutoff based on RECIST v1.1

**Measure:** (Expansion part) The objective response rate based on RECIST v1.1

**Time Frame:** From the first study dose date until the date of documented complete response or partial response, assessed up to 24 months

**Description:** To assess the time from the first documentation of complete response or partial response to the date of first documentation of disease progression or death (whichever occurs first) based on mRECIST and RECIST v1.1

**Measure:** Duration of response based on mRECIST and RECIST v1.1

**Time Frame:** up to 24 months

**Description:** To assess the time from the first study dose date to the date of first documentation of disease progression or death(whichever occurs first) based on mRECIST and RECIST v1.1

**Measure:** Progression-free survival based on mRECIST and RECIST v1.1

**Time Frame:** up to 24 months

**Description:** To assess the time from the first study dose date to the date of first documentation of disease progression based on mRECIST and RECIST v1.1

**Measure:** Time to progression based on mRECIST and RECIST v1.1

**Time Frame:** up to 24 months

**Description:** To assess the time from the date of first study dose to the date of first documentation of complete response or partial response based on mRECIST and RECIST v1.1

**Measure:** Time to response based on mRECIST and RECIST v1.1

**Time Frame:** up to 24 months

**Description:** To assess the proportion of subjects who have best overall response of complete response or partial response or stable disease (minimum duration from the initial treatment to stable disease ≥5 weeks) based on mRECIST and RECIST v1.1

**Measure:** Disease control rate based on mRECIST and RECIST v1.1

**Time Frame:** up to 24 months

**Description:** To assess the proportion of subjects who have best overall response of complete response or partial response or durable stable disease (duration of stable disease ≥ 23 weeks) based on mRECIST and RECIST v1.1

**Measure:** Clinical benefit rate based on mRECIST and RECIST v1.1

**Time Frame:** up to 24 months

**Description:** To assess the time from the first study dose date until date of death from any cause . Subjects who are lost to follow-up and the subjects who are alive at the date of data cutoff will be censored at the date the subject was last known alive or the cut-off date, whichever comes earlier.

**Measure:** Overall Survival

**Time Frame:** Throughout the entire course of treatment until the end of the follow-up period, an average of 2 years

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Males or females, aged 18 years or older.
2. Subjects must have confirmed diagnosis of HCC with any of the following criteria according to the American Association for the Study of Liver Diseases criteria.
3. Unresectable HCC.
4. Subjects were not eligible for locoregional or systemic therapies, or had disease progression, or would not benefit after at least one of the conventional therapies.
5. According to mRECIST, subjects should be with at least 1 measurable target lesion.
6. Life expectancy of 12 weeks or more.
7. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
8. Males with fertility and females of childbearing potential are willing to use a highly effective method of contraception for the entire study period and for 6 months after study drug discontinuation. Females of childbearing age, including premenopausal females and within 2 years after menopause, must have a negative serum pregnancy test result within 7 days prior to the first dose of study treatment.
9. Subjects who had a voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.

Exclusion Criteria:

1. Inadequate liver function：Albumin (ALB) \< 26 g/L, or total bilirubin \>5.0 mg/dL, or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or alanine aminotransferase (ALT) \>5 × the upper limit of normal (ULN).
2. Inadequate renal function defined as creatinine \>1.5 × ULN or calculated creatinine clearance \< 40 mL/min.
3. Absolute neutrophil count (ANC) \< 1.0×109/L, or Platelets \< 30×109/L, or Hemoglobin \< 8.5 g/dL.
4. International Normalized Ratio (INR) \> 2.3.
5. Subjects with a history of liver transplantation.
6. Subjects with poorly controlled hypertension, diabetes or other serious heart or lung diseases, or with serious dysfunction.
7. Subjects with extrahepatic metastasis who had not received first-line systemic therapies (excluding those who are not eligible for systemic therapies) or who were receiving effective systemic therapy currently.
8. Subjects who had prior anticancer treatment with any locoregional therapies, antiangiogenic targeted therapies, immune checkpoint inhibitors or chemotherapy (within 4 weeks, or within 2 weeks in case of sorafenib), radiotherapy (within 3 weeks), or active traditional Chinese medicine (within 2 weeks) before the first dose of study treatment, except for the treatments after which the disease still progressed according to mRECIST.
9. All toxicities related to prior locoregional or systemic anti-tumor treatments are still grade 2 or more (except for hair loss and other events that have been judged tolerable by researchers).
10. Subjects with complication histories of liver cirrhosis or HCC such as gastrointestinal hemorrhage, overt hepatic encephalopathy, or refractory ascites within 2 weeks prior to the first dose of study treatment.
11. Uncontrolled active infection (eg, lung infections, or abdominal infections).
12. History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival rate \> 90%), such as adequately treated early gastric carcinoma, carcinoma in situ of the cervix, non-melanoma skin carcinoma, or localized prostate cancer.
13. HBV DNA greater than 500 copies/mL, or HCV RNA greater than 15 U/mL.
14. Subject is positive for Human Immunodeficiency Virus (HIV).
15. Any subject who is allergic to MRI contrast agents.
16. Pregnant/lactating women, or women who have the possibility of pregnancy.
17. Participation in other investigational drug trials within 4 weeks prior to initiation of this study treatment.
18. Any medical or other condition which, in the opinion of the investigator, would preclude participation in this clinical trial.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** ilse1225@163.com

**Name:** CHUAN YIN, M.D.

**Phone:** +8613482705212

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Shanghai Changzheng Hospital

**Name:** Wei-Fen Xie, M.D.

**Role:** PRINCIPAL_INVESTIGATOR

## 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: 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

### 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: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- 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: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System 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: D000006528

- Term: Carcinoma, Hepatocellular

### Misc Info Module

- Version Holder: 2024-05-31
