Sorafenib Combined With Aspirin to Prevent the Recurrence in High-risk Patients With Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

A Prospective Randomized Control Trial of the Effect of Sorafenib Combined With Aspirin in Preventing the Recurrence in High-risk Patients With Hepatocellular Carcinoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02748304
• Other study ID #: Huashan 003
• Status: Terminated
• Phase: N/A
• Start date: April 2016
• Est. completion date: February 11, 2019

Study information

• Verified date: February 2019
• Source: Fudan University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to observe the effect of sorafenib combined with aspirin in preventing the recurrence in high-risk patients with hepatocellular carcinoma.

Description:

The recurrence of hepatocellular carcinoma(HCC）is the main problem during the treatment. Although some methods such as interferon may be effective in preventing the recurrence, there is still no clear effective approach widely accepted for everyone.

Sorafenib, a kind of tyrosine kinase inhibitor, which inhibiting proliferation and inducing apoptosis of tumor cell by inhibiting the raf/MEK/ERK pathway, and anti-angiogenesis by targeting Vascular Endothelial Growth Factor Receptor(VEGFR), has now become the standard treatment of advanced HCC patients. Although the STORM studies have shown that adjuvant sorafenib for such patients did not significantly affect recurrence-free survival, time to recurrence, or overall survival. The patients recruiting in the study were mostly early stage, for middle and late stage patients, whether sorafenib can reduce tumor recurrence after surgical resection and prolong survival remains to be further study.

Aspirin is a kind of nonsteroidal anti-inflammatory drugs. It is the first hint of aspirin's potential role in tumor prevention and treatment when Gasic found that tumor metastasis is reduced in thrombocytopenia mice, and then the research confirmed that aspirin treatment can significantly reduce the tumor metastasis. In recent years, a lot of epidemiological evidence and clinical trials found that aspirin played an important role in cancer prevention, at the same time, more experimental study has found that it can also play a role in tumor treatment. Our previous animal experiments found that a combination of sorafenib and aspirin can reverse the negative effect of sorafenib which promoted tumor metastasis, and obviously prolong survival of a tumor-burdened nude mice.

So, the study is to observe the effect of sorafenib combined with aspirin in preventing the recurrence in high-risk patients with hepatocellular carcinoma.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 52
• Est. completion date: February 11, 2019
• Est. primary completion date: February 11, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• The characteristics of the treatment history:

1. No sorafenib treatment history, no sorafenib allergies.

2. No chemotherapy, radiotherapy and transcatheter arterial chemoembolization(TACE) treatment history before surgery.

• The characteristics of the tumor:

1. The pathological results is hepatocellular carcinoma.

2. Meet any of the following articles:

• Pathological prompt microvascular invasion(MVI) class II, and incorporate any of the following:Tumor number>3,Tumor size>8cm,Tumor margin is not clear and no complete capsule.

• With the embolus in Portal vein, hepatic vein or bile duct.

• Preoperative rupture or invasion the adjacent organs.

• The positive cut edge.

• Residual lesions showed by Postoperative digital subtraction angiography(DSA).

• Alpha fetoprotein(AFP) did not drop to normal range two months after surgery.

• The characteristics of the patients:

1. The patient age was between 18-75.

2. The American Society of Anesthesiologists(ASA)score was I-III.

3. No history of esophageal varices and gastrointestinal bleeding.

4. The Child-pugh score was A.

5. Routine blood test: the leukocyte>2.5*10^9, platelet> 60*10^9.

6. The Prothrombin time was prolonged less than 2 second.

7. The Eastern Cooperative Oncology Group(ECOG) score was less than 2 points

Exclusion Criteria:

• Sorafenib treatment before surgery.

• Pregnant or lactating women.

• The Child-pugh score was B-C.

• Patients with other malignant tumor.

• Patients with mental illness.

• Patients participated in other clinical trials in last three months.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Recurrence

Intervention

Other:
• control
just follow up

Drug:
• sorafenib
sorafenib 400mg bid po
• aspirin
aspirin 100mg qd po

Locations

Country	Name	City	State
China	Huashan hospital	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

References & Publications (16)

Abiru S, Nakao K, Ichikawa T, Migita K, Shigeno M, Sakamoto M, Ishikawa H, Hamasaki K, Nakata K, Eguchi K. Aspirin and NS-398 inhibit hepatocyte growth factor-induced invasiveness of human hepatoma cells. Hepatology. 2002 May;35(5):1117-24. — View Citation

Bruix J, Takayama T, Mazzaferro V, Chau GY, Yang J, Kudo M, Cai J, Poon RT, Han KH, Tak WY, Lee HC, Song T, Roayaie S, Bolondi L, Lee KS, Makuuchi M, Souza F, Berre MA, Meinhardt G, Llovet JM; STORM investigators. Adjuvant sorafenib for hepatocellular car — View Citation

Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced — View Citation

De Simone P, Crocetti L, Pezzati D, Bargellini I, Ghinolfi D, Carrai P, Leonardi G, Della Pina C, Cioni D, Pollina L, Campani D, Bartolozzi C, Lencioni R, Filipponi F. Efficacy and safety of combination therapy with everolimus and sorafenib for recurrence — View Citation

Gasic GJ, Gasic TB, Murphy S. Anti-metastatic effect of aspirin. Lancet. 1972 Oct 28;2(7783):932-3. — View Citation

Gasic GJ, Gasic TB, Stewart CC. Antimetastatic effects associated with platelet reduction. Proc Natl Acad Sci U S A. 1968 Sep;61(1):46-52. — View Citation

Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003 Dec 6;362(9399):1907-17. Review. — View Citation

Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J, Gores GJ; Panel of Experts in HCC-Design Clinical Trials. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer I — View Citation

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, B — View Citation

Lu L, Sun HC, Zhang W, Chai ZT, Zhu XD, Kong LQ, Wang WQ, Zhang KZ, Zhang YY, Zhang QB, Ao JY, Li JQ, Wang L, Wu WZ, Tang ZY. Aspirin minimized the pro-metastasis effect of sorafenib and improved survival by up-regulating HTATIP2 in hepatocellular carcino — View Citation

Mahdi JG, Alkarrawi MA, Mahdi AJ, Bowen ID, Humam D. Calcium salicylate-mediated apoptosis in human HT-1080 fibrosarcoma cells. Cell Prolif. 2006 Aug;39(4):249-60. — View Citation

Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011 Jan 1;377(9759):31-41. doi: 10.1016/S0140-6736(10)62 — View Citation

Rothwell PM, Wilson M, Elwin CE, Norrving B, Algra A, Warlow CP, Meade TW. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet. 2010 Nov 20;376(9754):1741-50. doi: 10.1016/S0140-673 — View Citation

Saad-Hossne R, Prado RG, Hossne WS. Effects of acetylsalicylic acid and acetic acid solutions on VX2 liver carcinoma in rabbits. In vivo analysis. Acta Cir Bras. 2007 Jul-Aug;22(4):299-308. — View Citation

Sun HC, Tang ZY, Wang L, Qin LX, Ma ZC, Ye QH, Zhang BH, Qian YB, Wu ZQ, Fan J, Zhou XD, Zhou J, Qiu SJ, Shen YF. Postoperative interferon alpha treatment postponed recurrence and improved overall survival in patients after curative resection of HBV-relat — View Citation

Zhang W, Sun HC, Wang WQ, Zhang QB, Zhuang PY, Xiong YQ, Zhu XD, Xu HX, Kong LQ, Wu WZ, Wang L, Song TQ, Li Q, Tang ZY. Sorafenib down-regulates expression of HTATIP2 to promote invasiveness and metastasis of orthotopic hepatocellular carcinoma tumors in — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		5 years
Secondary	Disease free survival		5 years
Secondary	Number of patients with treatment-related bleedings who use aspirin		5 years