Toripalimab Plus Stereotactic Body Radiotherapy for HCC With PVTT

Toripalimab Plus Stereotactic Body Radiotherapy for Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: a Single-arm, Prospective Trial

To explore the efficacy and safety of toripalimab plus stereotactic body radiotherapy for hepatocellular carcinom with portal vein tumor thrombus.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Toripalimab; Radiation: Stereotactic body radiotherapy

Detailed Description

Programmed Cell Death Protein-1 (PD-1) was effective and tolerable in patients with advanced hepatocellular carcinoma. Additionally, previous studies showed that stereotactic body radiotherapy (SBRT) was effective for hepatocellular carcinoma with portal vein tumor thrombus (PVTT). No study has evaluated the efficacy and safety of toripalimab plus SBRT for hepatocellular carcinoma with PVTT. Thus, the investigators carried out this prospective study to find out it.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Cancer Center Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL)
• Patients must have at least one tumor lesion that can be accurately measured according to mRECIST criteria
• The normal liver volume in the non-target area was greater than 700ml
• Portal vein tumor thrumbus confirmed in two image techniques
• Eastern Cooperative Oncology Group performance status of 0 to 2
• No Cirrhosis or cirrhotic status of Child-Pugh class A only
• With no previous radiotherapy and immunotherapy
• Not applicable for transarterial chemoembolization, surgical resection, and local ablative therapy.
• The following laboratory parameters:

Platelet count ≥ 75,000/μL Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/ L Serum albumin ≥ 30 g/L ASL and AST ≤ 5 x upper limit of normal Serum creatinine ≤ 1.5 x upper limit of normal INR ≤ 1.5 or PT/APTT within normal limits Absolute neutrophil count (ANC) >1,500/mm3 Ability to understand the protocol and to agree to and sign a written informed consent document

Exclusion Criteria:

• Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy
• Known history of HIV
• History of organ allograft
• Known or suspected allergy to the investigational agents or any agent given in association with this trial.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
• Evidence of bleeding diathesis.
• Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry.
• Known central nervous system tumors including metastatic brain disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Toripalimab plus SBRT; Participants received 240mg toripalimab intravenously every 3 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. Participants recevied Stereotactic body radiotherapy. Radiotherapy dose was 36 ~ 54Gy, divided into 6 times of irradiation, and the radiation was performed within 2 weeks.	Drug: Toripalimab; 240mg intravenously every 3 weeks; Radiation: Stereotactic body radiotherapy; Radiotherapy dose was 36 ~ 54Gy, divided into 6 times of irradiation, and the radiation was performed within 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	PFS was defined as the time from the date of randomization to the date of first documentation of disease progression based on iRECIST, or date of death, whichever occurred first	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Number of adverse events. Postoperative adverse events were graded based on CTCAE v4.03	6 months
Overall survival (OS)	OS was defined as the duration from the date of randomization until the date of death from any cause. Participants who were lost to follow-up were censored at the last date the participant was known to be alive, and participants who remained alive were censored at the time of data cutoff.	6 months
Objective Response Rate (ORR)	ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) based on iRECIST. CR was defined as disappearance of any intratumoral arterial enhancement in all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of viable (enhancement of arterial phase) target lesions taking as reference to the baseline sum of the diameters of target lesions.	6 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2019
• Primary Completion (Anticipated): November 17, 2020
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: November 17, 2019
• First Submitted That Met QC Criteria: November 17, 2019
• First Posted (Actual): November 19, 2019

Study Record Updates

• Last Update Posted (Actual): November 19, 2019
• Last Update Submitted That Met QC Criteria: November 17, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Hepatocellular carcinoma; Toripalimab; Stereotactic body radiotherapy; Portal vein tumor thrombus
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: HCC-S1001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No