Liver CancerPhase 3NCT03949231
Infusion of PD1/PDL1/CTLA4 Inhibitors Via Hepatic Arterial for Immunotherapy of Hepatocellular Carcinoma
A Phase 3 study testing PD1/PDL1 inhibitor in people with Liver Cancer, run by Second Affiliated Hospital of Guangzhou Medical University at 1 site in China.
Trial summary
This trial was designed to investigate the survival outcomes, response rates, and safety of patients with Barcelona-Clinical Hepatocellular Carcinoma (BCLC)-C-stage liver cancer by hepatic artery versus vein infusion of PD1/PDL1/CTLA4 inhibitor or their combinations. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Liver Cancer
- What is being tested?
- PD1/PDL1 inhibitor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2019to 2 Jan 2038
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cytohistological confirmation is required for diagnosis of HCC.、
- Signed informed consent before recruiting
- Age between 18 to 80 years with estimated survival over 3 months.
- Child-Pugh class A or B/Child score > 7; ECOG score < 2
- Tolerable coagulation function or reversible coagulation disorders
- Laboratory examination test within 7 days prior to procedure: WBC≥3.0×10E9/L; Hb≥90g/L； PLT ≥50×10E9/L；INR < 2.3 or PT < 6 seconds above control；Cr ≤ 145.5 umul/L；Albumin > 28 g/L；Total bilirubin < 51 μmol/L
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- At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1.
- Patients with advanced (unresectable and/or metastatic, stage C based on Barcelona-Clinic Liver Cancer [BCLC] staging classification) hepatocellular carcinoma which would not be suitable for treatment with loco-regional therapies or have progressed following locoregional therapy such as surgical resection, percutaneous hepatic arterial embolization, radiofrequency ablation, and percutaneous interventional therapy.
- Birth control.
- Willing and able to comply with scheduled visits, treatment plan and laboratory tests.
Who cannot join
- Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks;
- Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding;
- Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;
- Patients accompanied with other tumors or past medical history of malignancy;
- Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during treatment;
- Patients have poor compliance.
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- Any contraindications for hepatic arterial infusion procedure:
- A.Impaired clotting test (platelet count < 60000/mm3, prothrombin activity < 50%).
- B.Renal failure / insufficiency requiring hemo-or peritoneal dialysis. C.Known severe atheromatosis. D.Known uncontrolled blood hypertension (> 160/100 mm/Hg).
- Patients have the past history of liver cancer treatment, such as transplantation, resection, radiotherapy, chemotherapy and so on;
- Allergic to adriamycin chemotherapy drugs，contrast agent and lipiodol;
- Any agents which could affect the absorption or pharmacokinetics of the study drugs
- Subjects unable to suffer the discomfort of the HAI procedure
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The Second Affiliated Hospital of Guangzhou Medical University
Guanzhou, Guangdong, 51260
Hui Lian, MD, 02034153532, lian-hui-2008@163.com
Zhenfeng Zhang, MD, PhD, +862039195966, zhangzhf@gzhmu.edu.cn
About this study
Official title: A Phase II/III Randomized Trial of Comparison of Survival Benefit of Administration of PD1/PDL1/CTLA4 Inhibitor or Their Combinations Via Hepatic Arterial Infusion Versus Vein for Immunotherapy of Advanced Liver Cancer
This trial was designed to investigate the survival outcomes, response rates, and safety of patients with Barcelona-Clinical Hepatocellular Carcinoma (BCLC)-C-stage liver cancer by hepatic artery versus vein infusion of PD1/PDL1/CTLA4 inhibitor or their combinations.
Read the detailed description
Liver cancer is the fifth most common malignancy worldwide, but the mortality rate ranks third. China has a large population base, with more than 400,000 new cases each year, and more than half of the world's new liver cancer and deaths. More than 70% of liver cancer patients in China are diagnosed at mid-to-late stage and have lost the chance of surgery. Only 10%-15% of newly diagnosed patients can undergo radical resection, and the recurrence rate after 5 years is as high as 50%-80%. So far, sorafenib is still the only standard treatment that can prolong the overall survival of advanced hepatocellular carcinoma. SHARP's latest research shows that sorafenib can only extend patients with advanced liver cancer for 2.8 months, and many adverse reactions; regofenib can be used in patients with advanced liver cancer after taking sorafenib resistance, but the overall efficiency is still low. It is difficult to be widely used in patients with advanced liver cancer, and more alternative therapies are urgently needed.
PD1/PDL1 inhibitor is widely used in treatment of various cancers in China now. The hepatic arterial chemotherapy infusion for advanced liver cancer, through the "first pass effect" of drug treatment, can significantly increase the local drug concentration of the tumor, improve the efficacy, reduce systemic adverse reactions, meanwhile Folfox regimen has been confirmed by the hepatic arterial chemotherapy infusion program. To the investigator's knowledge, no studies have been developed on the survival benefit of hepatic arterial infusion of immunotherapeutic agents in patients with advanced liver cancer. This phase III clinical trial was designed to compare the effects of PD1/PDL1/CTLA4 inhibitor or their combinations via IA and IV on the survival benefit of patients with advanced liver cancer, including ORR, DCR, median survival time, and safety.
- Conditions
- Liver Cancer
- Being tested
- PD1/PDL1 inhibitor
- Keywords
- Liver Cancer, PD1 antibody, Artery infusion, PDL1 antibody, CTLA4 antibody
- Medical subject headings
- Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD1/PDL1 inhibitorDrug
Also called Administration of PD1/PDL1 inhibitor through vein or interventional technique.
Infusion of PD1/PDL1 inhibitor through peripheral vein or hepatic artery.
| Study group | Role | What they receive |
|---|---|---|
| PD1/PDL1/CTLA4 inhibitor or their combinations hepatic artery infusion | Experimental | Interventional technique to place microcatheter in hepatic artery to infuse PD1/PDL1/CTLA4 inhibitor or their combinations in 30 minutes. Receives: Drug: PD1/PDL1 inhibitor |
| PD1/PDL1/CTLA4 inhibitor or their combinations vein infusion | Experimental | Regular IV infusion of PD1/PDL1/CTLA4 inhibitor or their combinations in 30 minutes. Receives: Drug: PD1/PDL1 inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Overall survival (OS) will be defined as the elapsed time from the enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact (or last date known to be alive). Follow-up for OS will occur every 12 weeks (±1 month) until death or withdrawal of consent from the study.
Measured: 2 years
Secondary outcomes (2)
Progression-free survival
Progression-free survival (PFS) will be defined as the elapsed time from the first date of study treatment until documented disease progression (as per mRECIST) or death from any cause, whichever is earlier. For patients who remain alive without progression, follow-up time will be censored at the date of last disease assessment.
Measured: 2 years
Adverse event rate
Adverse event rate will be defined as the rate of patients who developed adverse event.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2019
- Study start1 Jan 2019
- Primary completion1 Jan 2029 (estimated)
- Study completion2 Jan 2038 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CancerStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital of Guangzhou Medical 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hui Lian, MD, Principal investigator, Second Affiliated Hospital of Guangzhou Medical UniversityZhenfeng Zhang, MD, PhD, Principal investigator, Second Affiliated Hospital of Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03949231
- Sponsor's protocol ID
- ZZIAICI-008
- Status last verified
- Jun 2024
- First submitted
- 13 May 2019
- Last updated
- 26 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II/III Randomized Trial of Comparison of Survival Benefit of Administration of PD1/PDL1/CTLA4 Inhibitor or Their Combinations Via Hepatic Arterial Infusion Versus Vein for Immunotherapy of Advanced Liver Cancer
- ClinicalTrials.gov ID
- NCT03949231
- Acronym / sponsor ID
- ZZIAICI-008
- Conditions
- Liver Cancer
- Keywords
- Liver Cancer, PD1 antibody, Artery infusion, PDL1 antibody, CTLA4 antibody
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital of Guangzhou Medical UniversityUniversity, hospital or other
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 1 Jan 2029 (estimated)
- Study completion
- 2 Jan 2038 (estimated)
- First posted
- 14 May 2019 (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.
This trial was designed to investigate the survival outcomes, response rates, and safety of patients with Barcelona-Clinical Hepatocellular Carcinoma (BCLC)-C-stage liver cancer by hepatic artery versus vein infusion of PD1/PDL1/CTLA4 inhibitor or their combinations.
Detailed description
Liver cancer is the fifth most common malignancy worldwide, but the mortality rate ranks third. China has a large population base, with more than 400,000 new cases each year, and more than half of the world's new liver cancer and deaths. More than 70% of liver cancer patients in China are diagnosed at mid-to-late stage and have lost the chance of surgery. Only 10%-15% of newly diagnosed patients can undergo radical resection, and the recurrence rate after 5 years is as high as 50%-80%. So far, sorafenib is still the only standard treatment that can prolong the overall survival of advanced hepatocellular carcinoma. SHARP's latest research shows that sorafenib can only extend patients with advanced liver cancer for 2.8 months, and many adverse reactions; regofenib can be used in patients with advanced liver cancer after taking sorafenib resistance, but the overall efficiency is still low. It is difficult to be widely used in patients with advanced liver cancer, and more alternative therapies are urgently needed.
PD1/PDL1 inhibitor is widely used in treatment of various cancers in China now. The hepatic arterial chemotherapy infusion for advanced liver cancer, through the "first pass effect" of drug treatment, can significantly increase the local drug concentration of the tumor, improve the efficacy, reduce systemic adverse reactions, meanwhile Folfox regimen has been confirmed by the hepatic arterial chemotherapy infusion program. To the investigator's knowledge, no studies have been developed on the survival benefit of hepatic arterial infusion of immunotherapeutic agents in patients with advanced liver cancer. This phase III clinical trial was designed to compare the effects of PD1/PDL1/CTLA4 inhibitor or their combinations via IA and IV on the survival benefit of patients with advanced liver cancer, including ORR, DCR, median survival time, and safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PD1/PDL1/CTLA4 inhibitor or their combinations hepatic artery infusion | Experimental | Drug: PD1/PDL1 inhibitorInterventional technique to place microcatheter in hepatic artery to infuse PD1/PDL1/CTLA4 inhibitor or their combinations in 30 minutes. |
| PD1/PDL1/CTLA4 inhibitor or their combinations vein infusion | Experimental | Drug: PD1/PDL1 inhibitorRegular IV infusion of PD1/PDL1/CTLA4 inhibitor or their combinations in 30 minutes. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Cytohistological confirmation is required for diagnosis of HCC.、
- Signed informed consent before recruiting
- Age between 18 to 80 years with estimated survival over 3 months.
- Child-Pugh class A or B/Child score > 7; ECOG score < 2
- Tolerable coagulation function or reversible coagulation disorders
Key exclusion criteria (13 listed)
- Patients participated in clinical trials of equipment or drugs (signed informed consent) within 4 weeks;
- Patients accompany by ascites, hepatic encephalopathy and esophageal and gastric varices bleeding;
- Any serious accompanying disease, which is expected to have an unknown, impact on the prognosis, include heart disease, inadequately controlled diabetes and psychiatric disorders;
- Patients accompanied with other tumors or past medical history of malignancy;
- Pregnant or lactating patients, all patients participating in this trial must adopt appropriate birth control measures during 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 |
|---|---|---|
| PD1/PDL1 inhibitorAlso: Administration of PD1/PDL1 inhibitor through vein or interventional technique.Infusion of PD1/PDL1 inhibitor through peripheral vein or hepatic artery. | Drug | PD1/PDL1/CTLA4 inhibitor or their combinations hepatic artery infusion, PD1/PDL1/CTLA4 inhibitor or their combinations vein infusion |
Primary outcome
Overall survival
Time frame: 2 years
Overall survival (OS) will be defined as the elapsed time from the enrollment to death from any cause. For surviving patients, follow-up will be censored at the date of last contact (or last date known to be alive). Follow-up for OS will occur every 12 weeks (±1 month) until death or withdrawal of consent from the study.
2 secondary outcomes
Progression-free survival
Time frame: 2 years
Adverse event rate
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2024.
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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.
Hui Lian, MD principal investigator
Second Affiliated Hospital of Guangzhou Medical University
Zhenfeng Zhang, MD, PhD principal investigator
Second Affiliated Hospital of Guangzhou Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PD1/PDL1 inhibitor in people with Liver Cancer, run by Second Affiliated Hospital of Guangzhou Medical University at 1 site 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 13 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: looking for participants now, as of the sponsor's last update on 26 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hui Lian, MD (02034153532, lian-hui-2008@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: 2 years). 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 26 Jun 2024.