## Protocol Section
### Identification Module
**NCT ID:** NCT04943679

**Brief Title:** Anti-PD-1/PD-L1 Antibodies Plus Pegylated Interferon Alfa-2b Treatment in Patients With Advanced-Stage HCC

**Official Title:** Phase I/II Study of Anti-PD-1/PD-L1 Antibodies Combined With Pegylated Interferon Alfa-2b in Patients With Advanced-Stage Hepatocellular Carcinoma

#### Organization Study ID Info
**ID:** B20210618
#### Organization
**Class:** OTHER
**Full Name:** Shanghai Zhongshan Hospital
### Status Module
#### Completion Date
**Date:** 2024-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-03-31

**Type:** ACTUAL

**Last Update Submit Date:** 2022-03-28

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2024-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2021-06-15

**Type:** ACTUAL

**Status Verified Date:** 2022-03

#### Study First Post Date
**Date:** 2021-06-29
**Type:** ACTUAL
**Study First Submit Date:** 2021-06-21
**Study First Submit QC Date:** 2021-06-21
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Shanghai Zhongshan Hospital

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**Brief Summary:** This study is being done to analyze the safety, tolerability, and efficacy of treatment using combination of Pegylated Interferon Alfa-2b and anti-PD-1/PD-L1 antibodies for patients with advanced hepatocellular carcinoma.

**Detailed Description:** This is a study of combination anti-PD-1/PD-L1 antibodies and peginterferon alfa-2b for adult patients (≥18) with advanced hepatocellular carcinoma. Each 21 day dosing period will constitute a cycle.

Pegylated Interferon Alfa-2b has been proven to prolong the survival of HCC patients. Pegylated Interferon Alfa-2b is given subcutaneously, weekly during each 21-day cycle, for at least 6 cycles (18 weeks). Treatment may continue until disease progression, intolerable toxicity, or consent withdrawal.

Anti-PD-1/PD-L1 antibodies (including pembrolizumeb, nivolumab, sintilimab, toripalimab, camrelizumeb, tislelizumab and atezolizumab etc.) are given intravenously at assigned dose. Treatment may continue until disease progression, intolerable toxicity, or consent withdrawal.

This study is aimed to evaluate the safety and efficacy of the combination of Pegylated Interferon Alfa-2b and PD-1/PD-L1 mAb in unresectable late-stage HCC patients.

### Conditions Module

**Conditions:**

- Hepatocellular Carcinoma

**Keywords:**

- Hepatocellular Carcinoma

- Anti-PD-1 antibody

- Interferon Alfa

- Anti-PD-L1 antibody

### Design Module

#### Design Info

**Observational Model:** COHORT

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 15

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Peginterferon alfa-2b: 3 µg/kg every week by subcutaneous injection for up to 2 years; Anti-PD-1/PD-L1 Antibodies: given by intravenous injection at indicated dose for up to 2 years

**Intervention Names:**

- Drug: Anti-PD-1/PD-L1

- Drug: PEG-Interferon Alfa

**Label:** Anti-PD-1/PD-L1 antibodies and Pegylated Interferon Alfa-2b

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Anti-PD-1/PD-L1 antibodies and Pegylated Interferon Alfa-2b

**Description:** Intravenous injection for up to 2 years

**Name:** Anti-PD-1/PD-L1

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Anti-PD-1/PD-L1 antibodies and Pegylated Interferon Alfa-2b

**Description:** 3 µg/kg every week by subcutaneous injection for up to 2 years

**Name:** PEG-Interferon Alfa

**Other Names:**

- Pegasys

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Safety will be monitored by addressing and recording all adverse events (AEs), serious adverse events (SAEs) and specific laboratory abnormalities (worst grade). Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.

**Measure:** Incidence of adverse events

**Time Frame:** Up to 30 days after last treatment dose

#### Secondary Outcomes

**Description:** Evaluated by researchers based on the RECIST 1.1 standard

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

**Time Frame:** 2 years

**Description:** Evaluated by researchers based on the RECIST 1.1 standard

**Measure:** Progression free survival(PFS) [ Time Frame: 2 years ]

**Time Frame:** 2 years

**Description:** Evaluated by researchers based on the RECIST 1.1 standard

**Measure:** To the relief time (TOR)

**Time Frame:** 2 years

**Description:** Evaluated by researchers based on the RECIST 1.1 standard

**Measure:** Duration of relief(DOR)

**Time Frame:** 2 years

**Description:** Evaluated by researchers based on the RECIST 1.1 standard

**Measure:** Disease Control Rate (DCR)

**Time Frame:** 2 years

**Description:** Evaluated by researchers based on the RECIST 1.1 standard

**Measure:** 9-month survival rate

**Time Frame:** 9-month

**Description:** Evaluated by researchers based on the RECIST 1.1 standard

**Measure:** 12-month survival rate

**Time Frame:** 12-month

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. ≥18 years old, male or female
2. Advanced hepatocellular carcinoma (cannot be removed or metastasized) diagnosed clinically or pathologically, at least one measurable lesion without local treatment, Child-Pugh A ;Barcelona Clinic Liver Cancer(BCLC) staging is stage B or C
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
4. Patient has given written informed consent.
5. The function of important organs meets the requirements
6. Expected survival ≥12 weeks
7. Non-surgical sterilization or women of childbearing age need to use a medically-accepted contraceptive (such as an intrauterine device, contraceptive or condom) during the study period and within 3 months after the end of the study treatment period.

Exclusion Criteria:

1.The patient has any active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroid Hyperfunction; patients with vitiligo; complete remission of asthma in childhood, can be included without any intervention after adulthood; asthma patients who require bronchodilators for medical intervention cannot be included); 2.The patient is using immunosuppressive agents or systemic hormonal therapy to achieve immunosuppressive purposes (agents amount \> 10 mg / day of prednisone or other therapeutic hormones), and continue to use within 2 weeks before enrollment; 3.Have clinical symptoms or disease that are not well controlled 4.Significant clinically significant bleeding symptoms or a clear bleeding tendency within 3 months prior to randomization 5.Arterial/venous thrombosis in the first 6 months of randomization 6.According to the investigator, the patient has other factors that may affect the results of the study or lead to the termination of the study, such as alcohol abuse, drug abuse, other serious diseases (including mental illness) requiring combined treatment, and serious laboratory abnormalities.，with family or social factors, it will affect the safety of patients.

7.Liver tumor burden greater than 50% of the total liver volume, or patients who have previously undergone liver transplantation;Known for a history of central nervous system metastasis or hepatic encephalopathy;Severe allergic reactions to other monoclonal antibodies;

-

**Maximum Age:** 90 Years

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** Advanced HCC patients who received the combination therapy with Anti-PD-1/PD-L1 Antibodies Plus Pegylated Interferon Alfa-2b Treatment

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** 191784843@qq.com

**Name:** Jing Ma, M.D.

**Phone:** +86 18721278764

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Shanghai

**Contacts:**

***Contact 1:***

- **Email:** 191784843@qq.com

- **Name:** Jin Ma

- **Phone:** +86 18721278764

- **Role:** CONTACT

**Country:** China

**Facility:** Zhongshan Hospital, Fudan University

**Status:** RECRUITING

**Zip:** 200032

#### Overall Officials

**Official 1:**

**Affiliation:** Fudan University

**Name:** Yang Xu, M.D.&Ph.D

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Ji J, Shi J, Budhu A, Yu Z, Forgues M, Roessler S, Ambs S, Chen Y, Meltzer PS, Croce CM, Qin LX, Man K, Lo CM, Lee J, Ng IO, Fan J, Tang ZY, Sun HC, Wang XW. MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med. 2009 Oct 8;361(15):1437-47. doi: 10.1056/NEJMoa0901282.

**PMID:** 19812400

**Citation:** Davar D, Wang H, Chauvin JM, Pagliano O, Fourcade JJ, Ka M, Menna C, Rose A, Sander C, Borhani AA, Karunamurthy A, Tarhini AA, Tawbi HA, Zhao Q, Moreno BH, Ebbinghaus S, Ibrahim N, Kirkwood JM, Zarour HM. Phase Ib/II Study of Pembrolizumab and Pegylated-Interferon Alfa-2b in Advanced Melanoma. J Clin Oncol. 2018 Oct 25;36(35):JCO1800632. doi: 10.1200/JCO.18.00632. Online ahead of print.

**PMID:** 30359157

**Citation:** Finn RS, Ryoo BY, Merle P, Kudo M, Bouattour M, Lim HY, Breder V, Edeline J, Chao Y, Ogasawara S, Yau T, Garrido M, Chan SL, Knox J, Daniele B, Ebbinghaus SW, Chen E, Siegel AB, Zhu AX, Cheng AL; KEYNOTE-240 investigators. Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial. J Clin Oncol. 2020 Jan 20;38(3):193-202. doi: 10.1200/JCO.19.01307. Epub 2019 Dec 2.

**PMID:** 31790344

**Citation:** Zhou J, Sun H, Wang Z, Cong W, Wang J, Zeng M, Zhou W, Bie P, Liu L, Wen T, Han G, Wang M, Liu R, Lu L, Ren Z, Chen M, Zeng Z, Liang P, Liang C, Chen M, Yan F, Wang W, Ji Y, Yun J, Cai D, Chen Y, Cheng W, Cheng S, Dai C, Guo W, Hua B, Huang X, Jia W, Li Y, Li Y, Liang J, Liu T, Lv G, Mao Y, Peng T, Ren W, Shi H, Shi G, Tao K, Wang W, Wang X, Wang Z, Xiang B, Xing B, Xu J, Yang J, Yang J, Yang Y, Yang Y, Ye S, Yin Z, Zhang B, Zhang B, Zhang L, Zhang S, Zhang T, Zhao Y, Zheng H, Zhu J, Zhu K, Liu R, Shi Y, Xiao Y, Dai Z, Teng G, Cai J, Wang W, Cai X, Li Q, Shen F, Qin S, Dong J, Fan J. Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2019 Edition). Liver Cancer. 2020 Dec;9(6):682-720. doi: 10.1159/000509424. Epub 2020 Nov 11.

**PMID:** 33442540

## 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: 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: D000006528

- Term: Carcinoma, Hepatocellular

### Intervention Browse Module - Ancestors

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000000998

- Term: Antiviral Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: ANeo

- Name: Antineoplastic Agents

### Intervention Browse Module - Browse Leaves

- ID: M4225

- Name: Antibodies

- Relevance: LOW

- As Found: Unknown

- ID: M10184

- Name: Immunoglobulins

- Relevance: LOW

- As Found: Unknown

- ID: M10407

- Name: Interferons

- Relevance: HIGH

- As Found: Recurrent

- ID: M254669

- Name: Peginterferon alfa-2b

- Relevance: LOW

- As Found: Unknown

- ID: M19243

- Name: Interferon-alpha

- Relevance: HIGH

- As Found: Status

- ID: M247369

- Name: Peginterferon alfa-2a

- Relevance: LOW

- As Found: Unknown

- ID: M1685

- Name: Interferon alpha-2

- Relevance: LOW

- As Found: Unknown

- ID: M4314

- Name: Antiviral Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000007372

- Term: Interferons

- ID: D000016898

- Term: Interferon-alpha

### Misc Info Module

- Version Holder: 2024-05-24
