Adjuvant Therapy With Anlotinib for HCC

Hepatocellular Carcinoma Clinical Trial

Official title:

Adjuvant Therapy With Anlotinib Hydrochloride for Patients With Hepatocellular Carcinoma Who Underwent Curative Resection: a Single Arm Study

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04947371
• Other study ID #: HCC-ANO-ADJ
• Status: Withdrawn
• Phase: Phase 2
• Start date: December 15, 2018
• Est. completion date: March 30, 2019

Study information

• Verified date: June 2021
• Source: Shanghai Zhongshan Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 30, 2019
• Est. primary completion date: March 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Anlotinib Hydrochloride
Oral anlotinib hydrochloride 12 mg/d

Locations

Country	Name	City	State
China	Zhongshan Hospital, Fudan University	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Zhongshan Hospital

Country where clinical trial is conducted

China, 

References & Publications (2)

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. Erratum in: JAMA Oncol. 2018 Nov 1;4(11):1625. — View Citation

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. Erratum in: Chin Med J (Engl). 2017 Dec 20;130(24):3020. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events rate	The rates of severity and seriousness of the adverse events. Adverse events are graded according to the NCI-CTCAE (Version 5.0)	12 months
Secondary	Recurrence-free survival	From the date of liver surgery to the date of diagnosis of tumor recurrence or death from any cause	24 months
Secondary	Overall survival	From the date of liver surgery to the date of death from any cause	24 months