RT+ Anti-PD-1 for Patients With Advanced HCC (RT+PD-1-HCC)

Hepatocellular Carcinoma Clinical Trial

Official title:

Combining Radiation Therapy With Anti-PD-1 for Patients With Advanced Hepatocellular Carcinoma (RT+PD-1-HCC)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04193696
• Other study ID #: RT+PD-1-HCC
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 10, 2020
• Est. completion date: July 30, 2020

Study information

• Verified date: January 2020
• Source: Guangxi Medical University
• Contact: Bang-De Xiang, MD
• Phone: 86-771-5330855
• Email: xiangbangde[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 39
• Est. completion date: July 30, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Age 18-70 years

• Diagnosis of advanced HCC was confirmed by histopathological examination or clinical diagnosis, consistent with the following two conditions:

1. Extrahepatic metastasis with more than one measurable lesion;

2. 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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Guangxi Medical University

References & Publications (6)

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. — View Citation

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. — View Citation

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. Review. — View Citation

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, Häussinger 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. — View Citation

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. — View Citation

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. Erratum in: Lancet Oncol. 2018 Sep;19(9):e440. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate		6 months
Secondary	Overall survival		1 year
Secondary	Abscopal effects rate		6 months