Hepatocellular CarcinomaPhase 4NCT03515369
Effect of Babaodan on Tumor Recurrence After Curative Resection of Hepatocellular Carcinoma
A Phase 4 study testing Babaodan oral capsule in people with Hepatocellular Carcinoma and Tumor Recurrence, run by Eastern Hepatobiliary Surgery Hospital.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma, Tumor Recurrence
- What is being tested?
- Babaodan oral capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 459 participants
- Where
- No sites listed yet
- Study dates
- May 2018to Jun 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age ≥18 years and ≤75 years
- male or female patients
- tumor of BCLC A or B stage (≤3 nodules), and was assessed to be curative resected
- hepatocellular carcinoma confirmed by postoperative pathology, received R0 resection
- without tumor thrombus
- without extrahepatic metastasis
Show all 11Show fewer
- KPS score ≥80
- Child-Pugh A liver function
- the expected postoperative survival time ≥12 weeks
- 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
- agree to sign the informed consent
Who cannot join
- >3 tumor nodules
- history of HCC
- 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
- with serious diseases of heart, brain, lung, kidney and blood system
- received preoperative anti-cancer treatment
- received radiotherapy or chemotherapy during the operation
Show all 14Show fewer
- pregnant or lactating women
- receiving other clinical trials
- history of allogeneic organ transplantation
- patients known or suspected to be allergic to Babaodan, have allergy history of biological agents, have allergic constitution or being allergic
- patients with hemorrhagic tendency or history of gastrointestinal bleeding within 30 days; severe esophageal varices or have history of esophageal variceal hemorrhage
- cannot take medicine orally
- have HIV infection or AIDS related diseases
- have a history of mental illness or behavioral abnormality, which is assessed not suitable for clinical trials.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Effect of Babaodan in Preventing Tumor Recurrence After Hepatectomy for Hepatocellular Carcinoma: a Multicenter, Randomized, Placebo-controlled, Double-blind Trial
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
Read the 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.
- Conditions
- Hepatocellular Carcinoma, Tumor Recurrence
- Being tested
- Babaodan oral capsule, Placebo oral capsule
- Keywords
- hepatocellular carcinoma, tumor recurrence, adjuvant therapy, traditional Chinese medicine
- Medical subject headings
- Carcinoma, Hepatocellular, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Babaodan oral capsuleDrug
Also called Conventional liver protecting treatment
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.
Placebo oral capsuleDrug
Also called Conventional liver protecting treatment
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.
| Study group | Role | What they receive |
|---|---|---|
| Hepatectomy plus Babaodan | Experimental | Surgical removal of all lesions and take Babaodan oral capsule after operation Receives: Drug: Babaodan oral capsule |
| Hepatectomy plus Placebo | Placebo comparator | Surgical removal of all lesions and take Placebo oral capsule after operation Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
3-year disease free survival
the proportion of individuals who didn't have tumor recurrence and still alive 3 years after hepatectomy
Measured: 3-year
Secondary outcomes (3)
disease free survival
the time from hepatectomy until tumor recurrence, death or the last follow-up time
Measured: assessed up to 5 years
overall survival
the time from hepatectomy until death or the last follow-up time
Measured: assessed up to 5 years
EORTC QLQ-C30
a questionnaire developed to assess the quality of life of cancer patients
Measured: through study completion, an average of 3 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2018
- Study startMay 2018 (estimated)
- Primary completionJan 2022 (estimated)
- Study completionJun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 459 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eastern Hepatobiliary Surgery Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Zhongshan Hospital, Meng Chao Hepatobiliary Hospital of Fujian Medical University, 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.
- Responsible party
- Principal investigator, Shen Feng, Eastern Hepatobiliary Surgery Hospital
- Investigators
- Feng Shen, MD, PhD, Study chair, Eastern Hepatobiliary Surgery Hospital, Shanghai, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03515369
- Sponsor's protocol ID
- EHBHKY2017-01-016
- Status last verified
- May 2018
- First submitted
- 11 Apr 2018
- Last updated
- 3 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Babaodan in Preventing Tumor Recurrence After Hepatectomy for Hepatocellular Carcinoma: a Multicenter, Randomized, Placebo-controlled, Double-blind Trial
- ClinicalTrials.gov ID
- NCT03515369
- Acronym / sponsor ID
- EHBHKY2017-01-016
- Conditions
- Hepatocellular Carcinoma, Tumor Recurrence
- Keywords
- hepatocellular carcinoma, tumor recurrence, adjuvant therapy, traditional Chinese medicine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 459 participants (estimated)
- Lead sponsor
- Eastern Hepatobiliary Surgery HospitalUniversity, hospital or other
- Collaborators
- Shanghai Zhongshan Hospital, Meng Chao Hepatobiliary Hospital of Fujian Medical University, 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.
- Study start
- May 2018 (estimated)
- Primary completion
- Jan 2022 (estimated)
- Study completion
- Jun 2022 (estimated)
- First posted
- 3 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hepatectomy plus Babaodan | Experimental | Drug: Babaodan oral capsuleSurgical removal of all lesions and take Babaodan oral capsule after operation |
| Hepatectomy plus Placebo | Placebo comparator | Drug: Placebo oral capsuleSurgical removal of all lesions and take Placebo oral capsule after operation |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- age ≥18 years and ≤75 years
- male or female patients
- tumor of BCLC A or B stage (≤3 nodules), and was assessed to be curative resected
- hepatocellular carcinoma confirmed by postoperative pathology, received R0 resection
- without tumor thrombus
Key exclusion criteria (14 listed)
- >3 tumor nodules
- history of HCC
- 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
- with serious diseases of heart, brain, lung, kidney and blood system
- received preoperative anti-cancer treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Babaodan oral capsuleAlso: Conventional liver protecting treatmentOn 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. | Drug | Hepatectomy plus Babaodan |
| Placebo oral capsuleAlso: Conventional liver protecting treatmentOn 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. | Drug | Hepatectomy plus Placebo |
Primary outcome
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
3 secondary outcomes
disease free survival
Time frame: assessed up to 5 years
overall survival
Time frame: assessed up to 5 years
EORTC QLQ-C30
Time frame: through study completion, an average of 3 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2018.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Feng Shen, MD, PhD study chair
Eastern Hepatobiliary Surgery Hospital, Shanghai, China
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Babaodan oral capsule in people with Hepatocellular Carcinoma and Tumor Recurrence, run by Eastern Hepatobiliary Surgery Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 May 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Feng Shen, MD, PhD (0086-21-81875005, shenfengehbh@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
3-year disease free survival (time frame: 3-year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2018.