Adjuvant Therapy With Anlotinib for HCC

NCT04947371 | Withdrawn Phase 2

• 1 other identifier: HCC-ANO-ADJ
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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).

Conditions

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma; anlotinib; adjuvant; surgery

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Recurrence-free survival

  24 months

• Overall survival

  24 months

Study Arms (1)

Anlotinib Hydrochloride

EXPERIMENTAL

Oral anlotinib 12 mg/d

Drug: Anlotinib Hydrochloride

Interventions

Anlotinib Hydrochloride DRUG

Oral anlotinib hydrochloride 12 mg/d

Also known as: AL3818

Anlotinib Hydrochloride

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Related 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.

  PMID: 30098152 BACKGROUND

• 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.

  PMID: 29133751 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

anlotinib

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

• Jia Fan, MD&PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

• Hui-Chuan Sun, MD&PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Surgery

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: July 1, 2021
• Study Start: December 15, 2018
• Primary Completion: March 30, 2019
• Study Completion: March 30, 2019
• Last Updated: July 1, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)