Hepatocellular CarcinomaPhase 4NCT05113290
Effect and Safety of Recombinant Human Adenovirus Type 5 in Advanced HCC With Stable Disease After Sorafenib Treatment
A Phase 4 study testing Recombinant Human Adenovirus Type 5 injection and Sorafenib in people with Hepatocellular Carcinoma, run by First Affiliated Hospital Xi'an Jiaotong University at 4 sites in China.
Trial summary
Sorafenib, as a first-line treatment for patients with advanced HCC, can significantly prolong the overall survival rate of patients. However, about 53-71% of patients showed stable disease (SD) after sorafenib treatment, and further studies to explore optimal therapy for these patients are still needed. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Recombinant Human Adenovirus Type 5 injection and Sorafenib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 4 sitesChina
- Study dates
- 28 Dec 2021to 1 Dec 2023
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥ 18 years and ≤ 70 years of age, male or female
- Histologically/radiologically diagnosed advanced unresectable hepatocellular carcinoma
- Patients had received sorafenib as systemic therapy for advanced HCC with radiographic assessment of Stable Disease (SD) according to mRECIST criteria
- ECOG performance status of 0-2
- Child-Pugh score ≤ 7
- At least one measurable target lesion according to mRECIST and at least one lesion ≥ 10 mm; the lesions previously treated by radiotherapy or local regional therapy must have imaging evidence of disease progression to be considered as target lesions
Show all 10Show fewer
- Life expectancy ≥ 3 months
- A) White blood cell count ≥ 3.0 × 10 ^ 9/L, absolute neutrophil count ≥ 3.0 × 10 ^ 9/L, platelet count ≥ 50 × 10 ^ 9/L, hemoglobin > 100 g/L; B) INR ≤ 1.5 times the upper limit of normal, APTT ≤ 1.5 times the upper limit of normal or PTT ≤ 1.5 times the upper limit of normal; C) Total bilirubin ≤ 2.5 times the upper limit of normal; ALT and AST ≤ 5 times the upper limit of normal; serum creatinine ≤ 1.5 times the upper limit of normal
- Voluntarily participate in this study and sign the informed consent
- Female patients of childbearing age or male patients with sexual partners of childbearing age should take effective contraceptive measures throughout the treatment period and 6 months after treatment
Who cannot join
- Pregnant or lactating women
- Diffuse liver cancer or tumor not amenable to mRECIST criteria
- Prior treatment with oncolytic virus (e.g., T-VEC)
- Patients who are known to be allergic to the study drug or its active ingredients
- Sorafenib administration < 14 days
- History of immunodeficiency or autoimmune disease, or chronic systemic steroid therapy or any form of immunosuppressive therapy within 7 days prior to enrollment
- Patients with any other unstable systemic disease or other malignancy that may reduce life expectancy
- Patients participate in another interventional clinical trial within 30 days
Trial locations and contacts
4 sites in 1 country.
China4 sites
Shaanxi Provincial People's Hospital
Xi'an, Shaanxi
Tangdu Hospital
Xi'an, Shaanxi
The First Affiliated Hospital of Xi 'an Jiaotong University
Xi'an, Shaanxi
The Second Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi
About this study
Official title: Effect and Safety of Recombinant Human Adenovirus Type 5 (H101) in Advanced Hepatocellular Carcinoma Patients With Stable Disease After Sorafenib Treatment: A Randomized, Parallel-Controlled Clinical Trial
Sorafenib, as a first-line treatment for patients with advanced HCC, can significantly prolong the overall survival rate of patients. However, about 53-71% of patients showed stable disease (SD) after sorafenib treatment, and further studies to explore optimal therapy for these patients are still needed.
Oncolytic viruses are a type of virus that can selectively replicate in tumor cells and then destroy tumor cells, of which recombinant human adenovirus type 5 (H101) is the first oncolytic virus drug which was approved in the world. Recent studies indicate that H101 shows anti-tumor effects on liver cancer and there may be a synergistic effect between recombinant human adenovirus type 5 and sorafenib in the inhabitation of hepatoma cells in vitro. This study aims to further verify the effect and safety of recombinant human adenovirus type 5 combined with sorafenib in the treatment of advanced hepatocellular carcinoma.
Read the detailed description
Primary liver cancer is the fourth most common malignant tumor and the second most lethal cause of tumor in China, mainly including Hepatocellular carcinoma (HCC) and Intrahepatic Cholangiocarcinoma. ICC) and HCC-ICC, among which hepatocellular carcinoma accounts for about 75% of all primary liver cancer, bringing a heavy disease burden to China's health system and society. At present, for patients with unresectable advanced liver cancer, the commonly used treatment options include transcatheter chemoembolization (TACE), systemic therapy and radiotherapy. Since the introduction of the molecular-targeted drug Sorafenib in 2007, a number of clinical studies have shown that sorafenib has benefits for patients with advanced liver cancer in different countries and regions and with different liver disease backgrounds. It has become the standard therapy for advanced HCC and has been recommended for first-line treatment of advanced HCC patients by guidelines of many countries. However, although sorafenib can significantly prolong the overall survival rate, about 53-71% of patients still show stable disease (SD) after treatment. For these patients, further exploration is needed to optimize the treatment.
Oncolytic viruses are a class of viruses that can selectively replicate in tumor cells and then lytic tumor cells. Among them, recombinant human adenovirus TYPE 5 H101 is the world's first commercially available oncolytic drug, which has been approved for the treatment of head and neck tumors in 2003. Recombinant human adenovirus type 5 (H101) is a kind of oncolytic adenovirus, which can selectively replicate in tumor cells with deficient tumor suppressor gene p53 by knocking out e1B-55KD gene and partial gene fragment (78.3 ~ 85.8μm) of E3 region of human adenovirus type 5. Based on the data from the head and neck tumor-related clinical trial of recombinant human adenovirus H101, the drug has been approved for the treatment of advanced nasopharyngeal carcinoma in China. Based the study found that in recent years, in addition to the head and neck cancer, human recombinant adenovirus type 5 H101 also displayed antitumor effect on liver cancer, and the selective killing effect of the low concentration H101 on liver cancer cell associated with p53 gene mutation, and the high concentration of H101 on liver cancer cell and immortalized the role of normal liver cells is not restricted by cell p53 status. In vitro studies showed that both H101 and sorafenib alone could significantly inhibit the proliferation and induce apoptosis of human hepatoma cell lines HepG2 and Hep3B, and the combined effect of the two drugs was more significant than that of single drug 16. The synergistic mechanism of recombinant adenovirus H101 and sorafenib may be related to the influence of Raf/MEK/ERK signaling pathway. Sorafenib can block Raf/MEK/ERK signal transduction pathway, thereby inhibiting angiogenesis, while down-regulating the expression level of anti-apoptotic protein McL-1, and further inducing apoptosis of tumor cells. Meanwhile, sorafenib can upregulate the expression of Coxsackie adenovirus receptor (CAR) on the surface of hepatocellular carcinoma cells, increase the sensitivity of tumor cells to adenovirus, and enhance the oncolytic effect of H101. In addition, H101 combined with sorafenib can also effectively inhibit the expression of VEGF, thereby inhibiting the proliferation of tumor cells.
Based on the human recombinant adenovirus type 5 show the joint sorafenib synergy and its potential for the curative effect of hepatocellular carcinoma, this research intends to carry out a prospectie, intrusive, single-arm study, further validation of human recombinant adenovirus type 5 joint sorafenib therapy efficacy and safety of primary liver cancer, provides evidence-based medical evidence to support for clinical medication.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Recombinant Human Adenovirus Type 5 injection, Sorafenib
- Keywords
- oncolytic virus
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Recombinant Human Adenovirus Type 5 injectionDrug
Intratumoral injection of lesions with dose of 3 vials (1.5 × 10^12 vp) if the sum of the maximum lesion diameters was > 10 cm, 2 vials (1.0 × 10^12 vp) if the sum of the maximum lesion diameters was ≤ 10 cm. The cycle is 21 days up to 2-5 cycles.
SorafenibDrug
Sorafenib will be administered as the original dose before enrollment, or be adjusted by the doctor according to the tolerance.
| Study group | Role | What they receive |
|---|---|---|
| H101+Sorafenib | Experimental | H101 combined with Sorafenib Receives: Drug: Recombinant Human Adenovirus Type 5 injection; Drug: Sorafenib |
| Sorafenib | Active comparator | Patients take Sorafenib only Receives: Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR) according to mRECIST criteria
MRECIST criteria are based on traditional RECIST V1.0 and combined with specific assessment of hepatocellular carcinoma (HCC) (active lesions vs. Necrosis/fibrous nodules) to evaluate the efficacy of HCC
Measured: From the first administration of the study drug to disease progression, occurrence of unacceptable toxicity, withdrawal of informed consent or termination of the study (assessed up to 24 months)
Secondary outcomes (5)
Changes from baseline in alpha-fetoprotein (AFP) serum levels
Alpha-fetoprotein (AFP) is a protein produced in the liver and also the most widely accepted serum biomarker used in the management of hepatocellular carcinoma (HCC). Monitoring the serum level of AFP may provide important prognostic value. The serum levels of AFP will be obtained at baseline before treatment and then monitored during treatment and follow-up (every six weeks) to evaluate the effect of investigated drugs.
Measured: 1 year
Disease control rate (DCR)
The disease control rate is the sum of complete response rate, partial response rate and disease stability rate, that is, the ratio of patients with complete response, partial response and disease stability to all assessable patients.
Measured: From the first administration of the study drug to disease progression, occurrence of unacceptable toxicity, withdrawal of informed consent or termination of the study (up to 1 year)
Progression-free survival (PFS)
The total length of time from the onset of treatment and the observation of disease progression or the occurrence of death from any cause
Measured: up to 1 year
1 year survival rate
The proportion of patients who survive 1years or more with each combination of treatments.
Measured: 1 year
Number of participants with adverse events
The number of patients who had a medical event during treatment that was not necessarily causally related to the drug used, according to CTCAE V5.0
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2021
- Study start28 Dec 2021
- Primary completion1 Dec 2023 (estimated)
- Study completion1 Dec 2023 (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.
- More trials run by First Affiliated Hospital Xi'an Jiaotong UniversityThe sponsor's other registered studies.
- 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
- None (open label)
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chang Liu, MD, Principal investigator, First Affiliated Hospital Xi'an Jiaotong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05113290
- Sponsor's protocol ID
- XJTU1AF2021LSK-160
- Status last verified
- Oct 2021
- First submitted
- 24 Oct 2021
- Last updated
- 27 Jan 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect and Safety of Recombinant Human Adenovirus Type 5 (H101) in Advanced Hepatocellular Carcinoma Patients With Stable Disease After Sorafenib Treatment: A Randomized, Parallel-Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT05113290
- Acronym / sponsor ID
- XJTU1AF2021LSK-160
- Conditions
- Hepatocellular Carcinoma
- Keywords
- oncolytic virus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- First Affiliated Hospital Xi'an Jiaotong UniversityUniversity, hospital or other
- Study start
- 28 Dec 2021 (actual)
- Primary completion
- 1 Dec 2023 (estimated)
- Study completion
- 1 Dec 2023 (estimated)
- First posted
- 9 Nov 2021 (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.
Sorafenib, as a first-line treatment for patients with advanced HCC, can significantly prolong the overall survival rate of patients. However, about 53-71% of patients showed stable disease (SD) after sorafenib treatment, and further studies to explore optimal therapy for these patients are still needed.
Oncolytic viruses are a type of virus that can selectively replicate in tumor cells and then destroy tumor cells, of which recombinant human adenovirus type 5 (H101) is the first oncolytic virus drug which was approved in the world. Recent studies indicate that H101 shows anti-tumor effects on liver cancer and there may be a synergistic effect between recombinant human adenovirus type 5 and sorafenib in the inhabitation of hepatoma cells in vitro. This study aims to further verify the effect and safety of recombinant human adenovirus type 5 combined with sorafenib in the treatment of advanced hepatocellular carcinoma.
Detailed description
Primary liver cancer is the fourth most common malignant tumor and the second most lethal cause of tumor in China, mainly including Hepatocellular carcinoma (HCC) and Intrahepatic Cholangiocarcinoma. ICC) and HCC-ICC, among which hepatocellular carcinoma accounts for about 75% of all primary liver cancer, bringing a heavy disease burden to China's health system and society. At present, for patients with unresectable advanced liver cancer, the commonly used treatment options include transcatheter chemoembolization (TACE), systemic therapy and radiotherapy. Since the introduction of the molecular-targeted drug Sorafenib in 2007, a number of clinical studies have shown that sorafenib has benefits for patients with advanced liver cancer in different countries and regions and with different liver disease backgrounds. It has become the standard therapy for advanced HCC and has been recommended for first-line treatment of advanced HCC patients by guidelines of many countries. However, although sorafenib can significantly prolong the overall survival rate, about 53-71% of patients still show stable disease (SD) after treatment. For these patients, further exploration is needed to optimize the treatment.
Oncolytic viruses are a class of viruses that can selectively replicate in tumor cells and then lytic tumor cells. Among them, recombinant human adenovirus TYPE 5 H101 is the world's first commercially available oncolytic drug, which has been approved for the treatment of head and neck tumors in 2003. Recombinant human adenovirus type 5 (H101) is a kind of oncolytic adenovirus, which can selectively replicate in tumor cells with deficient tumor suppressor gene p53 by knocking out e1B-55KD gene and partial gene fragment (78.3 ~ 85.8μm) of E3 region of human adenovirus type 5. Based on the data from the head and neck tumor-related clinical trial of recombinant human adenovirus H101, the drug has been approved for the treatment of advanced nasopharyngeal carcinoma in China. Based the study found that in recent years, in addition to the head and neck cancer, human recombinant adenovirus type 5 H101 also displayed antitumor effect on liver cancer, and the selective killing effect of the low concentration H101 on liver cancer cell associated with p53 gene mutation, and the high concentration of H101 on liver cancer cell and immortalized the role of normal liver cells is not restricted by cell p53 status. In vitro studies showed that both H101 and sorafenib alone could significantly inhibit the proliferation and induce apoptosis of human hepatoma cell lines HepG2 and Hep3B, and the combined effect of the two drugs was more significant than that of single drug 16. The synergistic mechanism of recombinant adenovirus H101 and sorafenib may be related to the influence of Raf/MEK/ERK signaling pathway. Sorafenib can block Raf/MEK/ERK signal transduction pathway, thereby inhibiting angiogenesis, while down-regulating the expression level of anti-apoptotic protein McL-1, and further inducing apoptosis of tumor cells. Meanwhile, sorafenib can upregulate the expression of Coxsackie adenovirus receptor (CAR) on the surface of hepatocellular carcinoma cells, increase the sensitivity of tumor cells to adenovirus, and enhance the oncolytic effect of H101. In addition, H101 combined with sorafenib can also effectively inhibit the expression of VEGF, thereby inhibiting the proliferation of tumor cells.
Based on the human recombinant adenovirus type 5 show the joint sorafenib synergy and its potential for the curative effect of hepatocellular carcinoma, this research intends to carry out a prospectie, intrusive, single-arm study, further validation of human recombinant adenovirus type 5 joint sorafenib therapy efficacy and safety of primary liver cancer, provides evidence-based medical evidence to support for clinical medication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| H101+Sorafenib | Experimental | Drug: Recombinant Human Adenovirus Type 5 injection, Drug: SorafenibH101 combined with Sorafenib |
| Sorafenib | Active comparator | Drug: SorafenibPatients take Sorafenib only |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients ≥ 18 years and ≤ 70 years of age, male or female
- Histologically/radiologically diagnosed advanced unresectable hepatocellular carcinoma
- Patients had received sorafenib as systemic therapy for advanced HCC with radiographic assessment of Stable Disease (SD) according to mRECIST criteria
- ECOG performance status of 0-2
- Child-Pugh score ≤ 7
Key exclusion criteria (8 listed)
- Pregnant or lactating women
- Diffuse liver cancer or tumor not amenable to mRECIST criteria
- Prior treatment with oncolytic virus (e.g., T-VEC)
- Patients who are known to be allergic to the study drug or its active ingredients
- Sorafenib administration < 14 days
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 |
|---|---|---|
| Recombinant Human Adenovirus Type 5 injectionIntratumoral injection of lesions with dose of 3 vials (1.5 × 10^12 vp) if the sum of the maximum lesion diameters was > 10 cm, 2 vials (1.0 × 10^12 vp) if the sum of the maximum lesion diameters was ≤ 10 cm. The cycle is 21 days up to 2-5 cycles. | Drug | H101+Sorafenib |
| SorafenibSorafenib will be administered as the original dose before enrollment, or be adjusted by the doctor according to the tolerance. | Drug | H101+Sorafenib, Sorafenib |
Primary outcome
Objective response rate (ORR) according to mRECIST criteria
Time frame: From the first administration of the study drug to disease progression, occurrence of unacceptable toxicity, withdrawal of informed consent or termination of the study (assessed up to 24 months)
MRECIST criteria are based on traditional RECIST V1.0 and combined with specific assessment of hepatocellular carcinoma (HCC) (active lesions vs. Necrosis/fibrous nodules) to evaluate the efficacy of HCC
5 secondary outcomes
Changes from baseline in alpha-fetoprotein (AFP) serum levels
Time frame: 1 year
Disease control rate (DCR)
Time frame: From the first administration of the study drug to disease progression, occurrence of unacceptable toxicity, withdrawal of informed consent or termination of the study (up to 1 year)
Progression-free survival (PFS)
Time frame: up to 1 year
1 year survival rate
Time frame: 1 year
Number of participants with adverse events
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2022.
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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.
Chang Liu, MD principal investigator
First Affiliated Hospital Xi'an Jiaotong University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Recombinant Human Adenovirus Type 5 injection and Sorafenib in people with Hepatocellular Carcinoma, run by First Affiliated Hospital Xi'an Jiaotong University at 4 sites in China.
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 10 inclusion and 8 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 27 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) according to mRECIST criteria (time frame: From the first administration of the study drug to disease progression, occurrence of unacceptable toxicity, withdrawal of informed consent or termination of the study (assessed up to 24 months)). 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 27 Jan 2022.