NCT04317248

Brief Summary

The effect of anti-tumor treatment is not satisfying in HBV-related hepatocellular carcinoma (HBV-HCC) for reasons that HBV-HCC carries highly heterogeneous antigens to facilitate cancer cells escaping from immune surveillance and constructs an immunosuppressive microenvironment. Correspondingly, multiple signals loaded dendritic cells vaccine can efficiently present T cells with antigens of HCC sensitize their antitumor properties meanwhile low dose cyclophosphamide (CY) can effectively improve the microenvironment of immunity. Therefore, we put forward a new scientific therapy called "multiple signals loaded dendritic cells vaccine combined low dose of cyclophosphamide" combining with radical surgery or TACE or targeted agents for patients with hepatocellular carcinoma to prolong their survival time.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
600

participants targeted

Target at P75+ for phase_2 hepatocellular-carcinoma

Timeline
Completed

Started Apr 2020

Shorter than P25 for phase_2 hepatocellular-carcinoma

Geographic Reach
1 country

4 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 7, 2019

Completed
6 months until next milestone

First Posted

Study publicly available on registry

March 23, 2020

Completed
9 days until next milestone

Study Start

First participant enrolled

April 1, 2020

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 30, 2022

Completed
Last Updated

October 29, 2020

Status Verified

October 1, 2020

Enrollment Period

2.1 years

First QC Date

October 7, 2019

Last Update Submit

October 28, 2020

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinomahepatitis BDendritic cells vaccinecell therapy

Outcome Measures

Primary Outcomes (1)

  • Progression-Free-Survival (PFS), month

    The time from randomization until first documented progression or death from any cause，whichever came first

    240 weeks

Secondary Outcomes (5)

  • serum AFP(alpha fetoprotein）, ng/ml

    240 weeks

  • serum PIVKA-II(Protein Induced by Vitamin K Absence or Antagonist-II), μg/L

    240 weeks

  • Overall Survival (OS), month

    240 weeks

  • tumor size, mm

    240 weeks

  • Number of participants with treatment-related adverse events

    240 weeks

Study Arms (6)

MSDCV immune therapy combined with radical surgery therapy

EXPERIMENTAL

Multiple Signals loaded Dendritic Cells Vaccine(MSDCV) immune therapy：one time every 4 weeks during 0 weeks to 20 weeks, about 5\*10\^7 cells per time, total 6 times; Hepatocellular Carcinoma Radical surgery therapy: one time at a good operation time before the first time of MSDCV immune therapy

Drug: CyclophosphamideBiological: Multiple Signals loaded Dendritic Cells Vaccine

Radical surgery therapy

NO INTERVENTION

Hepatocellular Carcinoma Radical surgery therapy: one time at a good operation time

MSDCV immune therapy combined with TACE therapy

EXPERIMENTAL

Multiple Signals loaded Dendritic Cells Vaccine(MSDCV) immune therapy：one time every 4 weeks during 0 weeks to 20 weeks, about 5\*10\^7 cells per time, total 6 times; Transcatheter Hepatic Arterial Chemoembolization (TACE) therapy: the first time of TACE therapy must perform before the first time of MSDCV immune therapy， then perform when necessary according to subjects condition

Drug: CyclophosphamideBiological: Multiple Signals loaded Dendritic Cells Vaccine

TACE therapy

NO INTERVENTION

Transcatheter Hepatic Arterial Chemoembolization (TACE) therapy: perform when necessary according to Subjects condition

MSDCV immune therapy combined with targeted agents therapy

EXPERIMENTAL

Multiple Signals loaded Dendritic Cells Vaccine(MSDCV) immune therapy：one time every 4 weeks during 0 weeks to 20 weeks, about 5\*10\^7 cells per time, total 6 times; Targeted agents therapy: Sorafenib or Lenvatinib. For Sorafenib: 0.4g twice daily; for Lenvatinib: 12mg/8mg per day according to subjects condition

Drug: CyclophosphamideBiological: Multiple Signals loaded Dendritic Cells Vaccine

Targeted agents therapy

NO INTERVENTION

Targeted agents therapy: Sorafenib or Lenvatinib. For Sorafenib: 0.4g twice daily; for Lenvatinib: 12mg/8mg per day according to subjects condition

Interventions

CyclophosphamideDRUG

Intravenous drip，250mg/m\^2 per time，two days before each times of MSDCV therapy，total 6 times, in order to improve the immunosuppressive microenvironment of tumor，reduce CD4+CD25+FOXP3+regulatory T cells (Tregs）

Also known as: Endoxan
MSDCV immune therapy combined with TACE therapyMSDCV immune therapy combined with radical surgery therapyMSDCV immune therapy combined with targeted agents therapy
Multiple Signals loaded Dendritic Cells VaccineBIOLOGICAL

one time every 4 weeks during 0 weeks to 20 weeks, about 5\*10\^7 cells per time, intravenous driptotal 6 times;

Also known as: MSDCV
MSDCV immune therapy combined with TACE therapyMSDCV immune therapy combined with radical surgery therapyMSDCV immune therapy combined with targeted agents therapy

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • In accordance with AASLD guidelines for the diagnosis of hepatocellular carcinoma，histology or imaging confirmed as primary hepatocellular carcinoma
  • Patients with history of hepatitis B infection
  • Male and female adult subjects (18～70 years old)
  • Patients haven't received radiation therapy or chemotherapy or immunotherapy
  • Normal renal function
  • Blood routine test: Hb\>=9g/dL, white cell count\>=1.5\*10\^9/L, platelet count\>=50\*10\^9/L
  • Liver function: bilirubin\<=50umol/L, aspartate aminotransferase (AST) or alanine aminotransferase(ALT)\<=5 times the upper limit of normal
  • Child-Pugh score\<=9
  • Human Chorionic Gonadotropin(HCG) test negative(-) if patients are women of reproductive ages
  • Women of reproductive ages promise to contracept until therapy course has been finished for 3 months
  • Patients who have signed up informed consents

You may not qualify if:

  • Extrahepatic metastasis of hepatocellular carcinoma oHistory of embolism, chemotherapy or radiation
  • History of major surgery in last 4 weeks
  • History of radiofrequency ablation in last 6 weeks
  • Acute infections in last 2 weeks
  • Child-Pugh scores\>9
  • Patients with hepatic encephalopathy
  • Patients with ascites needed drainage
  • Patients have history of other cancer
  • Patients have history of HIV
  • Pregnant women
  • Patients with severe diseases like cardiac dysfunction
  • Patients with mental illness that influence signing informed consents
  • HBV infection combined with other types of hepatitis
  • Patients with autoimmune diseases
  • Immunosuppressant drugs users
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Nanfang Hospital

Guangzhou, Guangdong, 510000, China

RECRUITING

Sun Yat-sen University Cancer center

Guangzhou, Guangdong, 510000, China

RECRUITING

Sun Yat-sen University

Guangzhou, Guangdong, 510000, China

RECRUITING

The Third Affiliated Hospital of Zhongshan University

Guangzhou, Guangdong, 510630, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, HepatocellularHepatitis B

Interventions

Cyclophosphamide

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver DiseasesBlood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitis

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Yuehua Huang, doctorate

    Third Affiliated Hospital, Sun Yat-Sen University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuehua HYuang, doctorate

CONTACT

0086-13822232795huangyh53@mail.sysu.edu.cn

Yifan Lian, doctorate

CONTACT

0086-13824441190lianyf@mail3.sysu.edu.cn

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Laboratory director of hepatology，Deputy director of infection

Study Record Dates

First Submitted

October 7, 2019

First Posted

March 23, 2020

Study Start

April 1, 2020

Primary Completion

April 30, 2022

Study Completion

April 30, 2022

Last Updated

October 29, 2020

Record last verified: 2020-10

Data Sharing

IPD Sharing
Will not share

Locations

CN(4)