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Adjuvant Therapy With Anlotinib for HCC

Phase 2
Withdrawn
Conditions
Hepatocellular Carcinoma
Interventions
Registration Number
NCT04947371
Lead Sponsor
Shanghai Zhongshan Hospital
Brief Summary

Patients with high risk of disease recurrence after curative resection for hepatocellular carcinoma (HCC) deserve active intervention. However, there's limited treatment choice for these patients. Anlotinib hydrochloride, a multitarget tyrosine kinase inhibitor for both tumor angiogenesis and proliferative signaling in cancer cells, is approved in China for the 3rd line treatment of advanced non-small cell lung cancer. In the current study, we are to evaluate the safety and effects of adjuvant anlotinib therapy for the patients who underwent curative resection for HCC with high risk of tumor recurrence, which is defined by Shanghai Score (Sun, et al. Chin Med J (Engl) 2017).

Detailed Description

Patients with high risk of disease recurrence after curative resection for hepatocellular carcinoma (HCC) deserve active intervention. However, there's limited treatment choice for these patients. Anlotinib hydrochloride, a multitarget tyrosine kinase inhibitor for both tumor angiogenesis and proliferative signaling in cancer cells, is approved in China for the 3rd line treatment of advanced non-small cell lung cancer. In the current study, we are to evaluate the safety and effects of adjuvant anlotinib therapy for the patients who underwent curative resection for HCC with high risk of tumor recurrence, which is defined by Shanghai Score (Sun, et al. Chin Med J (Engl) 2017).

The primary outcome of this study is treatment safety, and the secondary outcome is recurrence-free survival and overall survival.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • Aged from 18-75 years.
  • HCC diagnosis was confirmed by pathological examination and those who did not receive anti-tumor treatment (anti-tumor treatment including but not limited to: local ablation therapy, TACE, radiation therapy, chemotherapy, targeted drug therapy, immunotherapy, and etc.)
  • Underwent curative resection for HCC with high risk of tumor recurrence, which was defined by Shanghai Score ≥ 4.922 (Sun, et al. Chin Med J (Engl) 2017)
  • Child-Pugh class: A or B7
  • The ECOG Performance Status: 0-1 points
  • The expected survival time ≥ 6 months
  • No disease recurrence 4-6 weeks after surgery as evaluated by abdominal contrast-enhanced CT/MRI and chest CT.
  • Adequate organs function
  • Complete blood counting HB ≥ 90 g/L ANC ≥ 1.5×10^9 /L PLT ≥ 75×10^9/L
  • Blood biochemistry ALB ≥ 28 g/L ALT and AST< 5×ULN TBIL ≤ 2×ULN Serum creatinine ≤ 1×ULN
  • Women of childbearing age must have pregnancy tests within 7 days prior to admission, and the results are negative and are willing to use appropriate methods of contraception at 8 weeks after the trial and at the end of the trial. For men, surgical sterilization should be applied, or consent to use appropriate methods of contraception 8 weeks after the trial and at the end of the trial.
  • Subjects voluntarily participated in the study, signed informed consent, good compliance in drug therapy and followed up.
Exclusion Criteria
  • Cholangiocarcinoma, the combination of cholangiocarcinoma of HCC, or fibrolamellar HCC diagnosed by pathology examination.

  • Past or current diagnosed with other malignancy, except skin basal cell carcinoma and cervical carcinoma in situ.

  • Those treated with liver or other organ transplantation or willing to undergo liver transplantation.

  • The conditions not suitable for oral medications, including difficulty swallowing, chronic diarrhoea, or bowel obstruction.

  • Vascular events within 6 months, including stroke and transient ischemic attack

    , deep venous thrombosis or pulmonary artery embolism.

  • Alimentary tract hemorrhage or high risk of alimentary tract hemorrhage due to esophageal varices, active ulcerative lesions or ulcerative colitis; or fecal occult blood test ≥ ++, or for those with fecal occult blood test (+), gastroscopy is required.

  • Abnormal coagulation function (international normalized ratio > 2, prothrombin time > 16 s, thrombin time >21s, activated partial thromboplastin time > 21 s, or fibrinogen < 2 g/L); or other conditions with bleeding tendency or undergoing thrombolysis or anticoagulant therapy.

  • Other severe or uncontrolled comorbidities:

  • hypertension and the blood pressure was not well managed by medications (systolic pressure ≥ 150 mmHg or diastolic pressure ≥ 90 mmHg); level 2 or higher myocardial ischemia or myocardial infarction, uncontrolled arrhythmia (including QTc interval ≥ 480 ms); level 1 heart dysfunction; or LVEF < 50%.

  • active or uncontrolled infection.

  • uncontrolled diabetes (fasting blood glucose > 10 mmol/L).

  • Urinary protein ≥ ++ or 24 hours urine protein > 1 g.

  • Unhealed wounds, ulcer, or bone fracture.

  • Those with mental illness or a history of psychotropic substance abuse; HIV infection.

  • Other conditions that the investigators considered that not suitable for trial inclusion.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Anlotinib HydrochlorideAnlotinib HydrochlorideOral anlotinib 12 mg/d
Primary Outcome Measures
NameTimeMethod
Adverse events rate12 months

The rates of severity and seriousness of the adverse events. Adverse events are graded according to the NCI-CTCAE (Version 5.0)

Secondary Outcome Measures
NameTimeMethod
Recurrence-free survival24 months

From the date of liver surgery to the date of diagnosis of tumor recurrence or death from any cause

Overall survival24 months

From the date of liver surgery to the date of death from any cause

Trial Locations

Locations (1)

Zhongshan Hospital, Fudan University

🇨🇳

Shanghai, Shanghai, China

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