Effect of Babaodan on Tumor Recurrence After Curative Resection of Hepatocellular Carcinoma
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|ClinicalTrials.gov Identifier: NCT03515369|
Recruitment Status : Not yet recruiting
First Posted : May 3, 2018
Last Update Posted : May 3, 2018
|Condition or disease||Intervention/treatment||Phase|
|Hepatocellular Carcinoma Tumor Recurrence||Drug: Babaodan oral capsule Drug: Placebo oral capsule||Phase 4|
Hepatocellular carcinoma (HCC) is the sixth most common malignancy and third leading cause of cancer-related mortality worldwide. Partial hepatectomy and liver transplantation are potential curative treatments for selected patients with HCC. Unfortunately, long-term surgical outcomes remain unsatisfactory due to high tumor recurrence rates, which has been reported to 40%-70%.
There are few methods for the prevention of HCC recurrence following curative-intent therapy, and no standard treatment has been established so far for recurrent tumor. The effective prevention of recurrence is the key to improve the management of this fatal malignancy. The protective role of transarterial chemoembolization (TACE) has been confirmed in advanced HCC, but the value of it as an adjuvant therapy is still controversial, which is mainly reflected in the inconsistent conclusions of the randomized controlled trials and the retrospective studies. Most prospective studies demonstrated that TACE was not effective or even harmful to postoperative tumor recurrence. Lai et al used combination therapy (lipiodol, cisplatin and epirubicin) as an adjuvant method for HCC patients after hepatectomy, and showed that the 3-year overall survival rate did not improve (66% vs. 65%), and the 3-year disease-free survival rate even decreased (18% vs. 48%) for the treatment group compared with the control group. However, retrospective studies indicate that postoperative adjuvant TACE is effective in preventing recurrence.
Immunotherapy shows its potential anti-tumor value, but its exact effect still needs further confirmation and the treatment standards is still uncertain. Compared with other solid tumors, liver cancer often has a background of hepatitis B virus (HBV) infection, so immunotherapy (such as thymosin, interferon) theoretically can simultaneously enhance the anti-tumor and anti HBV immunity, and even reduce tumor recurrence. Studies have reported that interferon treatment can improve the disease-free survival and overall survival of selected patients. Oral nucleoside antiviral drugs can improve the disease-free survival of HCC, because the hepatitis activity affects prognosis. But, the above results still need to be verified by large sample clinical trials.
Babaodan, a mixed powder of traditional Chinese medicine containing eight constituents, including natural calculus bovis, snake gall, antelope horn, pearl, musk, radix notoginseng and so on. The formula of Babaodan was protected by Chinese Food and Drug Administration. It has been widely used as a complementary and alternative medicine to treat chronic liver diseases, mitigate the side effects and enhance the efficacy of chemotherapeutic drugs, and promote cellular immunity. Lei et al reported that Babaodan can ameliorate liver injury and fibrosis in rat hepatic fibrosis model induced by diethylnitrosamine, and have no obvious side effect in normal rat livers. They also found that Babaodan did not influence the absorption of lipopolysaccharide (LPS) in liver by analysing serum from portal vein. Meanwhile, the results illustrated Babaodan can inhibit LPS-induced HSCs activation and proliferation in vitro through TLR4/NF-κB and TLR4/ERK signaling pathway, respectively. Upon these results, Babaodan may be a novel therapeutic choice for hepatic fibrosis. It also has been reported to have an effect of inhibiting the occurrence and development of HCC. However, the effect of Babaodan in preventing tumor recurrence is unclear.
In view of this, the investigators aim to implement a randomized controlled trial to assess whether oral Babaodan adjuvant therapy can effectively prevent tumor recurrence after curative resection for HCC patients, improve the quality of life, and evaluate the short-term and long-term safety of this drug.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||459 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Effect of Babaodan in Preventing Tumor Recurrence After Hepatectomy for Hepatocellular Carcinoma: a Multicenter, Randomized, Placebo-controlled, Double-blind Trial|
|Estimated Study Start Date :||May 2018|
|Estimated Primary Completion Date :||January 2022|
|Estimated Study Completion Date :||June 2022|
Experimental: Hepatectomy plus Babaodan
Surgical removal of all lesions and take Babaodan oral capsule after operation
Drug: Babaodan oral capsule
On the basis of conventional liver protecting treatment, take Babaodan oral capsule within 4 weeks after curative resection. Take two capsules three times daily, two months as a course of treatment and the maximum of eighteen courses, until the recurrence of tumor or death of patients (non tumor related death), or the termination of research.
Other Name: Conventional liver protecting treatment
Placebo Comparator: Hepatectomy plus Placebo
Surgical removal of all lesions and take Placebo oral capsule after operation
Drug: Placebo oral capsule
On the basis of conventional liver protecting treatment, take Placebo oral capsule began within 4 weeks after curative resection. Take two capsules three times daily, two months as a course of treatment and the maximum of eighteen courses, until the recurrence of tumor or death of patients (non tumor related death), or the termination of research.
Other Name: Conventional liver protecting treatment
- 3-year disease free survival [ Time Frame: 3-year ]the proportion of individuals who didn't have tumor recurrence and still alive 3 years after hepatectomy
- disease free survival [ Time Frame: assessed up to 5 years ]the time from hepatectomy until tumor recurrence, death or the last follow-up time
- overall survival [ Time Frame: assessed up to 5 years ]the time from hepatectomy until death or the last follow-up time
- EORTC QLQ-C30 [ Time Frame: through study completion, an average of 3 year ]a questionnaire developed to assess the quality of life of cancer patients
- safety and tolerability [ Time Frame: through study completion, an average of 3 year ]incidence of treatment-emergent adverse events
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03515369
|Contact: Feng Shen, MD, PhDfirstname.lastname@example.org|
|Contact: Kui Wang, MDemail@example.com|
|Study Chair:||Feng Shen, MD, PhD||Eastern Hepatobiliary Surgery Hospital, Shanghai, China|