NCT04193696

Brief Summary

Hepatocellular carcinoma (HCC) is a common malignancy, and its incidence is expected to increase in many countries in coming decades. Approximately 70-80% of newly diagnosed HCC patients already have advanced disease. Sorafenib and lenvatinib are recommended as first-line options for advanced HCC, the median overall survival of the patients with advanced HCC receiving sorafenib reached 10.7 months. Based on the results of phase II clinical studies and the recommendation of guidelines, the PD-1 monoclonal antibody, such as nivolumab and pembrolizumab, have been approved to treat the patients with advanced HCC by the FDA. PD-1 monoclonal antibody has been recommended as a second-line therapeutic strategy for HCC in the 2018 CSCO guidelines for the diagnosis and treatment of primary liver cancer. However, the results of existing studies indicate that the objective response rate (ORR) of first-line PD-1 antibody therapy for patients with advanced liver cancer is about 20%. There is a growing recognition of radiation-induced cancer cells-external tumor control mechanisms, in which radiation therapy(RT) contributes not only to local control of target lesions, but also to the control of metastases away from the treatment site. In recent years, RT combined with immunotherapy as a new treatment method has achieved certain curative effect in some patients with metastatic cancer. Therefore, it is interesting to investigate the efficacy of combining radiation therapy plus systemic anti-PD-1 immunotherapy for patients with advanced hepatocellular carcinoma.

Trial Health

35
At Risk

Trial Health Score

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

Trial has exceeded expected completion date
Enrollment
39

participants targeted

Target at P25-P50 for phase_2 hepatocellular-carcinoma

Timeline
Completed

Started Jan 2020

Shorter than P25 for phase_2 hepatocellular-carcinoma

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

December 9, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 10, 2019

Completed
1 month until next milestone

Study Start

First participant enrolled

January 10, 2020

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2020

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

July 30, 2020

Completed
Last Updated

January 9, 2020

Status Verified

January 1, 2020

Enrollment Period

6 months

First QC Date

December 9, 2019

Last Update Submit

January 7, 2020

Conditions

Hepatocellular Carcinoma

Keywords

advanced HCCanti-PD-1radiotherapy

Outcome Measures

Primary Outcomes (1)

  • Objective response rate

    6 months

Secondary Outcomes (2)

  • Overall survival

    1 year

  • Abscopal effects rate

    6 months

Study Arms (1)

radiotherapy plus PD-1

EXPERIMENTAL
Drug: Radiation therapy and systemic anti-PD-1 immunotherapy for patients with advanced hepatocellular carcinoma

Interventions

Radiation therapy and systemic anti-PD-1 immunotherapy for patients with advanced hepatocellular carcinomaDRUG

The treatment will be started within 1 week after being admitted into the trial. IMRT or SBRT are adopted , and dose of radiation: Dt-PGTV=40Gy/10fractions,Dt-PGTV=30Gy/10fractions,Dt-PGTV=20Gy/10fractions ,and so on.200mg/ of Carelizumab for injection will be given intravenously every 3 weeks for 5 times since the first day of radiotherapy until disease progression, or intolerable toxicity.

radiotherapy plus PD-1

Eligibility Criteria

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

You may qualify if:

  • Age 18-70 years
  • Diagnosis of advanced HCC was confirmed by histopathological examination or clinical diagnosis, consistent with the following two conditions:
  • Extrahepatic metastasis with more than one measurable lesion;
  • Intrahepatic multifocal lesions with more than one measurable lesion independent of the radiosurgery field
  • Patients have Child-Pugh A liver function
  • Expected survival ≥ 3 months
  • Unwilling to receive or unable to tolerate first-line treatment with sorafenib

You may not qualify if:

  • History of other malignancy
  • History of systemic immunotherapy
  • History of Radiation therapy within 6 months before the first administration
  • History of active autoimmune diseases requiring systemic treatment within 2 years before recruiting.
  • There are active infections that require systemic treatment
  • Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study
  • Pregnant or breast-feeding patients
  • Diagnosed with immunodeficiency or receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 7 days before the first administration of the study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (7)

  • Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.

    PMID: 18650514BACKGROUND

  • Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jan;10(1):25-34. doi: 10.1016/S1470-2045(08)70285-7. Epub 2008 Dec 16.

    PMID: 19095497BACKGROUND

  • Zhu AX, Finn RS, Edeline J, Cattan S, Ogasawara S, Palmer D, Verslype C, Zagonel V, Fartoux L, Vogel A, Sarker D, Verset G, Chan SL, Knox J, Daniele B, Webber AL, Ebbinghaus SW, Ma J, Siegel AB, Cheng AL, Kudo M; KEYNOTE-224 investigators. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018 Jul;19(7):940-952. doi: 10.1016/S1470-2045(18)30351-6. Epub 2018 Jun 3.

    PMID: 29875066BACKGROUND

  • El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. doi: 10.1016/S0140-6736(17)31046-2. Epub 2017 Apr 20.

    PMID: 28434648BACKGROUND

  • Herrera FG, Bourhis J, Coukos G. Radiotherapy combination opportunities leveraging immunity for the next oncology practice. CA Cancer J Clin. 2017 Jan;67(1):65-85. doi: 10.3322/caac.21358. Epub 2016 Aug 29.

    PMID: 27570942BACKGROUND

  • Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman MD, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015 Apr 16;520(7547):373-7. doi: 10.1038/nature14292. Epub 2015 Mar 9.

    PMID: 25754329BACKGROUND

  • Li JX, Su TS, Gong WF, Zhong JH, Yan LY, Zhang J, Li LQ, He ML, Zhang RJ, Du YQ, Wang XT, Liang SX, Xiang BD. Combining stereotactic body radiotherapy with camrelizumab for unresectable hepatocellular carcinoma: a single-arm trial. Hepatol Int. 2022 Oct;16(5):1179-1187. doi: 10.1007/s12072-022-10396-7. Epub 2022 Aug 24.

    PMID: 36001228DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Bang-De Xiang, MD

CONTACT

86-771-5330855xiangbangde@163.com

Jian-Xu Li, MD

CONTACT

86-771-5330855lijianxu1236@163.com

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: This stuy has only one arm.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

December 9, 2019

First Posted

December 10, 2019

Study Start

January 10, 2020

Primary Completion

June 30, 2020

Study Completion

July 30, 2020

Last Updated

January 9, 2020

Record last verified: 2020-01