Sorafenib Plus Toripalimab for Unresectable HCC With Portal Vein Tumor Thrombus

• Status: Unknown status
• Trial end date: 2021-10-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sichuan University
• Treatments: Sorafenib

Criteria

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.