Adjuvant Therapy With Apatinib for HCC Patients With PVTT Who Underwent Radical Resection

Phase 2

• Conditions: Carcinoma, Hepatocellular
• Interventions: Drug: Apatinib

• Registration Number: NCT03261791
• Lead Sponsor: Shanghai Zhongshan Hospital

Brief Summary

In this phase 2 study, we aim to evaluate the effects and safety of adjuvant apatinib therapy for the patients who underwent R0 resection for hepatocellular carcinoma with portal vein tumor thrombus.

Detailed Description

Portal vein tumor thrombus (PVTT) is one of the characteristics of advanced stage for patients with hepatocellular carcinoma (HCC). There's limited treatment choice for these patients. Even for those who underwent curative resection (R0 resection), the recurrence rate was extremely high. Apatinib is a highly selective VEGFR2 inhibitor and reduces the angiogenesis of tumor efficiently, which had been proven effective in many solid tumors, is a Chinese domestic TKI targeting vascular endothelial growth factor receptor. Phase 2 study of apatinib for patients with advanced HCC had shown signals of clinical efficacy and modest safety. In this study, we aim to evaluate the effects and safety of adjuvant apatinib therapy for the patients who underwent R0 resection for HCC with PVTT.

Study Timeline

• Study Start: 2017-07-20
• Status Verified: 2017-08
• Study First Submitted: 2017-08-23
• Study First Submitted QC: 2017-08-24
• Last Update Submitted: 2017-08-24
• Study First Posted: 2017-08-25
• Last Update Posted: 2017-08-25
• Primary Completion: 2020-01-20
• Study Completion: 2020-04-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Aged from 18-70 years.

2. HCC diagnosis confirmed by pathological examination 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, etc.)

3. Underwent radical resection for hepatocellular carcinoma with portal vein tumor thrombus, as assessed by preoperative imaging or intraoperative findings, within 4 weeks

4. Child-Pugh class: A or B7

5. The ECOG: 0-1 points

6. The expected survival time ≥ 6 months.

7. Main organs function is normal including:

   • blood routine examination

     • HB ≥ 90 g/L
     • ANC ≥ 1.5×109 /L
     • PLT ≥ 80×109/L

   • biochemical test

     • ALB ≥ 29 g/L
     • ALT<3 ULN and AST< 3 ULN
     • TBIL ≤ 1.5 ULN
     • Serum creatinine ≤ 1.5 ULN；

8. Women of childbearing age must have pregnancy tests (serum or urine) 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 test. For men, surgical sterilization should be applied, or consent to the appropriate method of contraception 8 weeks after the trial and at the end of the trial;

9. subjects voluntarily joined the study, signed informed consent, good compliance, and followed up.

Exclusion Criteria

1. Hepatic duct carcinoma、mixed cell carcinoma and fiberboard layer cell carcinoma which have confirmed; Past (5 years) or current with other malignant tumor, except skin basal cell carcinoma and cervical carcinoma in situ.
2. Patients with hypertension who are unable to fall within normal range by antihypertensive medications (systolic pressure > 140 mmHg, diastolic pressure > 90 mmHg).
3. With the second level of myocardial ischemia or myocardial infarction, poor control of the arrhythmia (including QTc interval = 450 ms, male female = 470 ms).
4. Factors that affect oral medication, such as inability to swallow, chronic diarrhea and intestinal obstruction, which significantly affect the use and absorption of drugs.
5. Ascites with clinical symptoms requires therapeutic peritoneal paracentesis or drainage.
6. In the past 6 months, with the history of alimentary tract hemorrhage or definite gastrointestinal bleeding tendency, such as: the risk of bleeding esophageal varices, local active ulcerative lesions, fecal occult blood; For those with fecal occult blood (+), gastroscopy is required.
7. Abdominal fistula, gastrointestinal perforation, or abdominal abscess occurred within 28 days before entry;
8. Postoperative complications were not relieved.
9. Abnormal coagulation function (INR > 1.5 or prothrombin time (PT) > ULN+4 seconds), with bleeding tendency or undergoing thrombolysis or anticoagulant therapy;
10. Past and present pulmonary fibrosis history, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug associated pneumonia, and severe lung function impairment;
11. Urine routine showed that urinary protein is more than + + or confirmed 24 hours urine protein is more than 1.0 g;
12. Symptomatic metastasis of the central nervous system;
13. Pregnant or lactating women; fertile patients who are unwilling or unable to adopt effective contraceptives;
14. Patient with mental illness or a history of psychotropic substance abuse;
15. HIV infection;
16. Before operation, AFP or PIVKA-2 increased, but not decreased to normal range;
17. HBV-DNA>10^3 copys/ml；
18. Other conditions that the investigators considered that not unsuitable for inclusion.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Apatinib	Apatinib	Apatinib mesylate tablets 500 mg po qd.

Primary Outcome Measures

Name	Time	Method
recurrence-free survival	24 months	From the date of liver surgery to the date of diagnosis of tumor recurrence

Secondary Outcome Measures

Name	Time	Method
overall survival	24 months	From the date of liver surgery to the date of death
safety: the potential side effects	24 months	The potential side effects

Trial Locations

Locations (1)

Zhongshan Hospital; 🇨🇳 Shanghai, Shanghai, China