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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
Sponsor:
Collaborators:
Shanghai Zhongshan Hospital
Fujian Mengchao Hepatobiliary Hospital
Sun Yat-sen University
First Affiliated Hospital, Sun Yat-Sen University
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Second Military Medical University
Xiamen Traditional Chinese Medicine Co., Ltd.
Information provided by (Responsible Party):
Shen Feng, Eastern Hepatobiliary Surgery Hospital

Brief Summary:
The aim of this study is to evaluate the effect of traditional Chinese medicine Babaodan on tumor recurrence of hepatocellular carcinoma after curative resection, as well as the safety of this treatment

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Tumor Recurrence Drug: Babaodan oral capsule Drug: Placebo oral capsule Phase 4

Detailed Description:

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Arm Intervention/treatment
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. disease free survival [ Time Frame: assessed up to 5 years ]
    the time from hepatectomy until tumor recurrence, death or the last follow-up time

  2. overall survival [ Time Frame: assessed up to 5 years ]
    the time from hepatectomy until death or the last follow-up time

  3. 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


Other Outcome Measures:
  1. safety and tolerability [ Time Frame: through study completion, an average of 3 year ]
    incidence of treatment-emergent adverse events



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. age ≥18 years and ≤75 years
  2. male or female patients
  3. tumor of BCLC A or B stage (≤3 nodules), and was assessed to be curative resected
  4. hepatocellular carcinoma confirmed by postoperative pathology, received R0 resection
  5. without tumor thrombus
  6. without extrahepatic metastasis
  7. KPS score ≥80
  8. Child-Pugh A liver function
  9. the expected postoperative survival time ≥12 weeks
  10. the latest laboratory tests met the following requirements before entering the group: 1) hemoglobin ≥8.5g/dl; 2) neutrophils count ≥1,000/mm3; 3) platelet count ≥50,000/ul; 4) total bilirubin ≤2 upper limit of normal; 5) ALT and AST ≤3 upper limit of normal; 6) serum urea nitrogen and creatinine ≤1.5 upper limit of normal
  11. agree to sign the informed consent

Exclusion criteria:

  1. >3 tumor nodules
  2. history of HCC
  3. history of other tumors, except: 1) in situ carcinoma of cervix; 2) treated basal cell carcinoma; 3) superficial bladder cancer (Ta、Tis and T1); 4) any cancer that received radical treatment more than 3 years
  4. with serious diseases of heart, brain, lung, kidney and blood system
  5. received preoperative anti-cancer treatment
  6. received radiotherapy or chemotherapy during the operation
  7. pregnant or lactating women
  8. receiving other clinical trials
  9. history of allogeneic organ transplantation
  10. patients known or suspected to be allergic to Babaodan, have allergy history of biological agents, have allergic constitution or being allergic
  11. patients with hemorrhagic tendency or history of gastrointestinal bleeding within 30 days; severe esophageal varices or have history of esophageal variceal hemorrhage
  12. cannot take medicine orally
  13. have HIV infection or AIDS related diseases
  14. have a history of mental illness or behavioral abnormality, which is assessed not suitable for clinical trials.

Information from the National Library of Medicine

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


Contacts
Contact: Feng Shen, MD, PhD 0086-21-81875005 shenfengehbh@sina.com
Contact: Kui Wang, MD 13636330827 wangkuiykl@163.com

Sponsors and Collaborators
Eastern Hepatobiliary Surgery Hospital
Shanghai Zhongshan Hospital
Fujian Mengchao Hepatobiliary Hospital
Sun Yat-sen University
First Affiliated Hospital, Sun Yat-Sen University
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Second Military Medical University
Xiamen Traditional Chinese Medicine Co., Ltd.
Investigators
Study Chair: Feng Shen, MD, PhD Eastern Hepatobiliary Surgery Hospital, Shanghai, China

Responsible Party: Shen Feng, Vice President, Professor and Chief Surgeon; Member-at-large of International Hepato-Pancreato-Biliary Association (IHPBA); Secretary of Asia-Pacific Hepato-Pancreato-Biliary Association (A-PHPBA), Eastern Hepatobiliary Surgery Hospital
ClinicalTrials.gov Identifier: NCT03515369     History of Changes
Other Study ID Numbers: EHBHKY2017-01-016
First Posted: May 3, 2018    Key Record Dates
Last Update Posted: May 3, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shen Feng, Eastern Hepatobiliary Surgery Hospital:
hepatocellular carcinoma
tumor recurrence
adjuvant therapy
traditional Chinese medicine

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Recurrence
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Disease Attributes
Pathologic Processes
Liver Extracts
Hematinics