Adjuvant Treatment of Patients With High Risk of Recurrent Hepatocellular Carcinoma With Donafenib in Combination With Envafolimab

NCT06498622 | Recruiting Phase 2 DMC

• 1 other identifier: 2023KY433
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multi-center, single arm study to evaluate the efficacy and safety of donafenib in combination with envafolimab treatment in patients with high risk of recurrent hepatocellular carcinoma after radical surgery.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• RFS

  Recurrence Free Survival \[Time Frame: Observation period 24 month\] RFS was defined as the time from randomization to the first documented occurrence of local, regional, or metastatic HCC or death from any cause, whichever first occurred.

  Observation period 24 months

Secondary Outcomes (4)

• OS

  24 months

• 2-year RFS rate

  Observation period 24 months

• 2-year OS rate

  24 months

• AEs

  24 months

Study Arms (1)

Donafenib 100mg PO bid + Envafolimab 300mg IH D1 q3w

EXPERIMENTAL

Donafenib：100mg，PO，bid；Treatment cycle 6-12 months Envafolimab：300mg, IH，D1，q3w；Treatment cycle 6-12 months or 8-16 sessions Donafenib and Envafolimab will be administered until the disease recurrence, intolerable toxicity, death, withdrawal of consent or completion of 16 cycles of Envafolimab.

Drug: Donafenib + Envafolimab

Interventions

Donafenib + Envafolimab DRUG

Drug: Envafolimab Envafolimab 300mg IH D1 q3w Other Name: Immunotherapy, Anti-PD-L1 antibody Drug: Donafenib Donafenib 100mg PO bid Other Name: tyrosine kinase inhibitor, TKI

Donafenib 100mg PO bid + Envafolimab 300mg IH D1 q3w

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old, male and female.
• Subjects voluntarily enrolled in this study and signed the informed consent, good compliance and co-operated with the follow-up.
• Primary hepatocellular carcinoma with postoperative histopathological diagnosis of HCC and negative margins.
• Presence of any of the following high-risk factors for recurrence: ① tumor size ≥5.0cm combined with microvascular invasion; ② number of tumors ≥3; ③ presence of portal vein cancer thrombus (vp1 or vp2 type).
• No recurrence of metastasis confirmed by imaging examination 3-7 weeks after surgery.
• ECOG score of 0-1.
• Expected survival ≥ 3 months.
• Child-Pugh score ≤ 7.
• Subjects with no previous antitumour therapy (except antiviral therapy)
• No extra-hepatic metastases or lymph node metastases.
• No significant abnormality in routine laboratory tests (blood test, liver and kidney function, coagulation function, etc.): (1) Criteria for routine blood tests need to be met (no blood and blood products transfusion within 14 days): a. Absolute neutrophil value (ANC) ≥ 1.5\*10\^9/L; b. Haemoglobin (HGB) ≥ 90g/L; c. Platelet count (PLT) ≥ 75\*10\^9/L. (2) Biochemical tests need to meet the following criteria: a. Serum albumin (ALB) ≥ 35g/L; b. Serum total bilirubin (TBIL) \< 1.5\*Upper Limit of Normal (ULN); c. Serum glutamic transaminase (AST), alanine aminotransferase (ALT) \< 2.5\*ULN; d. Serum creatinine ≤ 1.5\*ULN.

You may not qualify if:

• Previous histologically/cytologically confirmed fibroplaque-containing hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma and other components.
• Histologically confirmed positive resection margin (R1 resection), presence of lymph node metastasis or extrahepatic metastasis.
• Previous or current malignancy other than hepatocellular carcinoma.
• History of hepatic encephalopathy or history of liver transplantation.
• Previous history of allergy to any component of the test drug: Envafolimab monoclonal antibody, donafini.
• Subjects with poorly controlled persistent postoperative pleural, abdominal or pericardial effusion.
• Previous antitumour therapy (except antiviral therapy).
• History of interstitial lung disease (except radiation pneumonitis not treated with hormones), non-infectious pneumonia.
• Presence of any active autoimmune disease or history of autoimmune disease in the subject (e.g., the following, but not limited to: autoimmune hepatitis, interstitial pneumonitis, uveitis, enterocolitis, hepatitis, pituitary gland inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism subjects with vitiligo or asthma that has been in complete remission in childhood and does not require any intervention in adulthood may be enrolled subjects with asthma that requires medical intervention with bronchodilators cannot be included).
• Subjects who are on immunosuppressive, or systemic, or absorbable topical hormone therapy for immunosuppression (dose \>10mg/day prednisone or other equipotent hormone) and continue to use it within 2 weeks prior to enrolment.
• A serious infection (CTCAE \> grade 2) such as severe pneumonia, bacteraemia, or infectious co-morbidities requiring hospitalisation has occurred 4 weeks prior to the first use of study drug.
• Subjects who have experienced acute cardiovascular disease such as acute cerebral infarction, acute coronary syndrome, etc. within 1 month, with cardiovascular clinical symptoms or disease not well controlled.
• According to NYHA standard, grade III to IV cardiac insufficiency, or cardiac ultrasound examination suggests that the left ventricular ejection fraction (LVEF) \<50%
• Uncontrollable hypertension with treated systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg, hypertensive crisis or history of hypertensive encephalopathy
• Patients with a definite tendency to gastrointestinal bleeding, including the following: patients with locally active ulcerative lesions and fecal occult blood {(++) may not be enrolled} those with a history of black stools and vomiting of blood within 2 months.

Sponsors & Collaborators

• Anhui Provincial Hospital: lead

Study Sites (2)

No.2 People's Hospital of Fuyang city

Fuyang, Anhui, 236015, China

RECRUITING

Anhui province hospital

Hefei, Anhui, 230000, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

donafenib; envafolimab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Lianxin Liu

  Anhui Provincial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lianxin Liu

CONTACT

+86 18096656677; liulx@ustc.edu.cn

Ji-Zhou Wang

CONTACT

+86 13836135864; wangjoe@ustc.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2024
• First Posted: July 12, 2024
• Study Start: July 20, 2024
• Primary Completion (Estimated): May 20, 2027
• Study Completion (Estimated): May 20, 2027
• Last Updated: July 12, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)