Adjuvant Therapy With Anlotinib for HCC

NCT ID: NCT04947371

Last Updated: 2021-07-01

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-15
• Study Completion Date: 2019-03-30

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.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Anlotinib Hydrochloride

Oral anlotinib 12 mg/d

Group Type: EXPERIMENTAL

Anlotinib Hydrochloride

Intervention Type: DRUG

Oral anlotinib hydrochloride 12 mg/d

Interventions

Anlotinib Hydrochloride

Oral anlotinib hydrochloride 12 mg/d

Intervention Type: DRUG

Other Intervention Names

AL3818

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hui-Chuan Sun

Professor of Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jia Fan, MD&PhD

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Hui-Chuan Sun, MD&PhD

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Countries

China

References

Han B, Li K, Wang Q, Zhang L, Shi J, Wang Z, Cheng Y, He J, Shi Y, Zhao Y, Yu H, Zhao Y, Chen W, Luo Y, Wu L, Wang X, Pirker R, Nan K, Jin F, Dong J, Li B, Sun Y. Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non-Small Cell Lung Cancer: The ALTER 0303 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2018 Nov 1;4(11):1569-1575. doi: 10.1001/jamaoncol.2018.3039.

Reference Type: BACKGROUND

PMID: 30098152 (View on PubMed)

Sun HC, Xie L, Yang XR, Li W, Yu J, Zhu XD, Xia Y, Zhang T, Xu Y, Hu B, Du LP, Zeng LY, Ouyang J, Zhang W, Song TQ, Li Q, Shi YH, Zhou J, Qiu SJ, Liu Q, Li YX, Tang ZY, Shyr Y, Shen F, Fan J. Shanghai Score: A Prognostic and Adjuvant Treatment-evaluating System Constructed for Chinese Patients with Hepatocellular Carcinoma after Curative Resection. Chin Med J (Engl). 2017 Nov 20;130(22):2650-2660. doi: 10.4103/0366-6999.218019.

Reference Type: BACKGROUND

PMID: 29133751 (View on PubMed)

Other Identifiers

HCC-ANO-ADJ

Identifier Type: -

Identifier Source: org_study_id