Sorafenib Plus Toripalimab for Unresectable HCC With Portal Vein Tumor Thrombus (STUHCCPVTT)

October 23, 2019 updated by: Zhen-Yu Ding, Sichuan University

An Exploratory Study of Sorafenib Plus Toripalimab for Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus

This study aims to evaluate the efficacy and safety of sorafenib plus toripalimab for unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Investigators aimed to conduct an exploratory study- an open-label, single-arm and multi-center -to evaluate the efficacy and safety of sorafenib plus toripalimab for unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). The primary objectives are 6-month progression free survival (PFS) rate and safety. Secondary objectives include objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS) and duration of response. The study is divided into dose escalation stage and expansion stage.

Stage I (escalation stage) was designed to identify the dose-limiting toxicity (DLT) of the combination therapy. Subjects enrolled were divided into two cohorts. Subjects (n=3) in cohort A received oral sorafenib at doses of 400 mg once daily, in combination with intravenous toripalimab 240 mg on the first day, every 3 weeks. Subjects (n=3) in cohort B received oral sorafenib at doses of 400 mg twice daily, in combination with intravenous toripalimab 240 mg on the first day, every 3 weeks. If DLT does not occur within 42 days of the first administration, the dose is escalated. If one subject experienced DLTs, additional 3 subjects are enrolled at that level. Unless no DLT occurs, the next dose level test is continued.

Once ≥2 subjects in cohort A experienced DLT, the study is suspended in advance. If ≥2 subjects in cohort B experienced DLT, the dose of cohort A is recommended in expansion stage. If DLT does not occur in cohort B or only 1 of 6 subjects suffered DLT, the dose of cohort B is recommended in expansion stage.

For subjects who experienced DLT, if adverse events (AEs) return to normal or common terminology criteria for adverse events (CTCAE) level 1 within 2 weeks and researchers believe continuing treatment is beneficial to the subjects, they can continue treatment after dose adjustment. Otherwise, termination of treatment is suggested.

According to CTCAE version 4.0, DLT was defined as any grade ≥3 treatment-related toxicity occurring within the first 42 days of administration. Six to twelve patients will be included in this stage.

Stage II (Expansion stage): According to the expansion dose based on stage I, subjects are enlarged to 39. Subjects enrolled are treated with oral sorafenib in combination with toripalimab (every 3 weeks) until suffering progressive disease (PD) or un-tolerated toxicities. Previous literature indicated 6-month PFS rate for HCC with PVTT treated with sorafenib is about 20%. Investigators hypothesize sorafenib plus toripalimab could improve 6-month PFS rate to 40%. Software (PASS) is used to calculate the sample size (β=0.2，α=0.05). According to the results, 35 subjects should be enrolled. When 10% missing rate is considered, total subjects is 39.

Study Type

Interventional

Enrollment (Anticipated)

39

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Qiu Li, Professor
  • Phone Number: 86-028-85423609
  • Email: fbqiu9@163.com

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 74 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Histologic or cytologic diagnosis of unresectable hepatocellular carcinoma, or confirmed clinically in accordance with Chinese Association for the Study of Liver Diseases criteria (v2017)
  2. Radiographically measurable disease by RECIST version 1.1 in at least one site
  3. Radiographic evidence of portal vein cancer thrombus
  4. Survival expectation ≥3 months
  5. Eastern Cooperative Oncology Group: 0 or 1
  6. Child-Pugh score A or B: score ≤7
  7. Not previously treated with any systemic anti-cancer treatment (i.e. chemotherapy, target drugs, immune checkpoint inhibitors); Subjects who have received local hepatic therapy such as surgery, ablation, radiotherapy or transcatheter arterial chemoembolization, progression of target lesions after local treatment is required to increase by 25%, or target lesions are untreated, and the end of local treatment is more than 4 weeks.
  8. All eligible patients have adequate organ function (ANC ≥1.5× 10⁹ / L, PLT ≥75 × 10⁹ /L, HGB≥90 g/L (no blood transfusion or EPO tolerance within 7 days), Cr≤1.5 times the ULN, TBN ≤1.5 times ULN, ALT and AST ≤3 times ULN, albumin ≥30g/L (albumin or branched chain amino acids supplementation is not allowed within 14 days), INR≤1.5 times the ULN, Urine protein≤1+).
  9. Signed and dated written informed consent

Exclusion Criteria:

  1. History of severe allergic reactions to chimeric, human or humanized antibodies, or fusion proteins. Hypersensitive to any component of the CHO cell-derived preparation or JS001 preparation
  2. Pregnant or lactating women, men and women of childbearing age who are unwilling or unable to take effective contraceptive measures
  3. History of other malignancy within the past 5 years
  4. Medium or more pleural and ascites with clinical symptoms
  5. Active hemorrhage or abnormal coagulation function (PT>16s, APTT>43s, INR>1.5 x ULN), or having a tendency to bleed or undergoing thrombolysis, anticoagulation or anti-platelet therapy
  6. Central nervous system metastases
  7. Hepatic encephalopathy
  8. History of gastrointestinal bleeding or having a tendency to bleed within 6 months before enrollment, e.g. local active ulcer lesions; fecal occult blood (+ +) or above should not be included; if continuous fecal occult blood (+), gastroscopy should be performed.
  9. Gastric or esophageal varices requiring treatment
  10. Untreated active hepatitis B (i.e. subjects with hepatitis B undergoing antiviral therapy and HBV Load < 100IU/mL before the first administration of Toripalimab , is allowed to be enrolled; for subjects with anti-HBc (+), HBsAg (-), anti-HBs (-) and HBV viral load (-) , prophylactic anti-HBV therapy is not required, but virus activation should be closely monitored)
  11. HCV and the anti-HCV treatment ended within 4 weeks of the first administration. Notably, subjects with untreated chronic HCV infection or untreated HCV are allowed.
  12. History of drug abuse or mental disorders
  13. History of organ or marrow transplants, or active autoimmune diseases requiring systemic treatment occurred within 2 years of the first administration
  14. Immunodeficiency disorders or HIV
  15. Pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia and severe impairment of pulmonary function
  16. Using immunosuppressive agents or systemic or absorbable local corticosteroids for immunosuppressive purposes (prednisone or its equivalent at dose> 10 mg/day) , and the above are used within 2 weeks before admission.
  17. Major liver or other operations were performed within 4 weeks of the first administration, or minor operations were performed within 1 week before the first administration (simple excision, tooth extraction, etc.)
  18. Receiving vaccine within 30 days of the first administration
  19. Abdominal fistula, gastrointestinal perforation or abdominal abscess within 4 weeks of the first administration
  20. Receiving other experimental drugs or medical devices within 4 weeks of the first administration
  21. Any significant clinical and laboratory abnormalities that in the opinion of the investigator would affect safety assessment
  22. Failure to satisfy the investigator of fitness to participate for any other reason.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: sorafenib plus toripalimab

Stage I：Subjects (n=3) in cohort A received oral sorafenib (400 mg qd), in combination with intravenous toripalimab (240 mg d1, q3w). Subjects (n=3) in cohort B received oral sorafenib (400 mg bid) and the administration of toripalimab is consistent with cohort A. If dose-limiting toxicity (DLT) does not occur within 42 days of the first administration, the dose is escalated.

Stage II: According to the expansion dose based on stage I, subjects are enlarged to 39.
Drug: sorafenib; toripalimab
Stage I: cohort A: sorafenib 400 mg qd+ toripalimab 240 mg d1; q3w cohort B: sorafenib 400 mg bid, toripalimab 240 mg d1; q3w Stage II: According to the expansion dose based on stage I, subjects are enlarged to 39.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
6-month Progression Free Survival rate
Time Frame: up to 6 months
Proportion of patients with Progression Free Survival in 6-month
up to 6 months
Incidence of Treatment-Emergent Adverse Event
Time Frame: up to 6 months
Any adverse events related with treatment with Sorafenib Plus Toripalimab
up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate
Time Frame: up to 6 months
Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients
up to 6 months
Disease Control Rate
Time Frame: up to 6 months
Proportion of patients with stable disease, complete response and partial response
up to 6 months
Progression Free Survival
Time Frame: up to 6 months
A duration from the date of initial treatment with Sorafenib Plus Toripalimab to disease progression (defined by RECIST 1.1) or death of any cause.
up to 6 months
Overall Survival
Time Frame: up to 1 year
Duration from the date of initial treatment with Sorafenib Plus Toripalimab to the date of death due to any cause.
up to 1 year
Duration of response
Time Frame: From the date of study enrollment to the time of death from any cause, assessed up to 1 year
time from first documented complete or partial response to radiologically confirmed disease progression or death from any cause.
From the date of study enrollment to the time of death from any cause, assessed up to 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sichuan University

Investigators

  • Principal Investigator: Qiu Li, Professor, West China Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

December 1, 2019

Primary Completion (Anticipated)

October 1, 2020

Study Completion (Anticipated)

October 1, 2021

Study Registration Dates

First Submitted

August 24, 2019

First Submitted That Met QC Criteria

August 24, 2019

First Posted (Actual)

August 28, 2019

Study Record Updates

Last Update Posted (Actual)

October 25, 2019

Last Update Submitted That Met QC Criteria

October 23, 2019

Last Verified

October 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LQ108

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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