Clinical trial NCT02748304: Sorafenib Combined With Aspirin to Prevent the Recurrence in High-risk Patients With Hepatocellular Carcinoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Hepatocellular Carcinoma
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2016-04-22
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall survival
timeFrame: 5 years
Secondary outcomes:
measure: Disease free survival
timeFrame: 5 years
measure: Number of patients with treatment-related bleedings who use aspirin
timeFrame: 5 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan hospital
Study officials:
affiliation: Department of general surgery, Huashan hospital, Fudan University
name: Lunxiu Qin, MD
role: PRINCIPAL_INVESTIGATOR
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