HepatocarcinomaPhase 2/3NCT03755739
Trans-Artery/Intra-Tumor Infusion of Checkpoint Inhibitors Plus Chemodrug for Immunotherapy of Advanced Solid Tumors
A Phase 2/3 study testing Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapy in people with Hepatocarcinoma and Lung Cancer, run by Second Affiliated Hospital of Guangzhou Medical University at 1 site in China.
Trial summary
This trial was designed to investigate the safety, response rates and survival outcomes of patients with advanced solid tumors by trans-artery/intra-tumor infusion of PD1/PDL1 antibody and/or CTLA4 antibody ipilimumab plus chemotherapeutic drug and to compare their differences. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocarcinoma, Lung Cancer, Melanoma
- What is being tested?
- Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapy
- 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 Nov 2018to 1 Nov 2036
- Phase
- Phase 2/3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cytohistological confirmation is required for diagnosis of cancer.
- Signed informed consent before recruiting.
- Age above 18 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.
- 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).
- Allergic to contrast agent;
- Any agents which could affect the absorption or pharmacokinetics of the study drugs
- Other conditions that investigator decides not suitable for the trial.
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
Zhenfeng Zhang, MD,PhD, 02034153532, zhangzhf@gzhmu.edu.cn
About this study
Official title: A Phase II/III Trial of Comparison of Benefit of Administration of Checkpoint Inhibitors Plus Chemodrug Via Artery or Fine Needle to Tumor Versus Vein for Immunotherapy of Advanced Solid Tumors
This trial was designed to investigate the safety, response rates and survival outcomes of patients with advanced solid tumors by trans-artery/intra-tumor infusion of PD1/PDL1 antibody and/or CTLA4 antibody ipilimumab plus chemotherapeutic drug and to compare their differences.
Read the detailed description
Malignant solid tumors including lung and liver cancers are the most common malignancy worldwide, and their mortality rates are very high. China has a huge population base, with about 4,000,000 new cases each year. More than 60% of the solid tumors in China are diagnosed at mid-to-late stage and have lost the chance of surgery. Recently a lot of therapeutic strategies have been developed and applied to clinic including targeted therapy and immunotherapy, but the overall efficiency is still low. It is difficult to be widely used in patients with advanced solid cancers, and more alternative therapies are urgently needed.
Antibodies against PD1, PDL1 and CTLA4 are representative drugs for the check-points inhibitory agents, and their clinical indications have been approved in various types of tumors, including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin's lymphoma and late recurrent head and neck squamous cell carcinoma patients, et al. Those drugs are regularly systemically administrated by vein infusion, however, local delivery of those drugs via interventional radiology technique including trans-artery or intra-tumor injection may increase the local drug concentration in the tumor, improve the efficacy, and reduce systemic adverse reactions, through so called "first pass effect" of drug on target organs. To the investigator's knowledge, no studies have been developed on the efficacy and survival benefit of localized delivery of checkpoint inhibitors for treatment of cancer patients. This phase II-III clinical trial was designed to compare the effects of Pembrolizumab, Tecentriq, et al and/or ipilimumab plus chemotherapeutic drug such as doxorubicin on the survival benefit of patients with advanced solid cancers, including ORR, DCR, median survival time, and safety.
- Conditions
- Hepatocarcinoma, Lung Cancer, Melanoma, Renal Cancer, Head and Neck Cancer, Pancreas Cancer
- Being tested
- Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapy
- Keywords
- Solid cancers, Check-point inhibitors, Interventional Radiology, Trans-artery infusion, Intra-tumor injection
- Medical subject headings
- Carcinoma, Hepatocellular, Lung Neoplasms, Melanoma, Kidney Neoplasms, Head and Neck Neoplasms, Pancreatic Neoplasms, Ovarian Neoplasms, Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapyDrug
Also called Checkpoint inhibitor (CPI) such as Keytruda plus chemotherapy
vein, artery, or intra-tumor infusion of checkpoint inhibitor (CPI) such as Pembrolizumab and/or Ipilimumab, plus chemotherapy to destroy cancer cells and release tumor antigen for improving CPI therapeutic efficacy.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab via localized infusion | Experimental | This group dividied into two subgroups:
1. Checkpoint inhibitor (CPI) such as Pembrolizumab ± Ipilimumab is administrated with a dose of 1-2mg/kg via sustained (10min) micro-pump infusion via artery, plus chemotherapy, every 3 weeks.
2. Checkpoint inhibitor (CPI) such as Pembrolizumab ± Ipilimumab is administrated with a total dose of 150mg via intra-tumor fine needle injection in 5 min, plus doxorubicin, every 3 weeks. Receives: Drug: Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapy |
| Checkpoint inhibitor (CPI) Pembrolizumab plus chemotherapy via vein infusion | Active comparator | Checkpoint inhibitor (CPI) such as Pembrolizumab is administrated with a total dose of 2mg/kg via vein infusion (30 min), plus chemotherpy every 3 weeks. Receives: Drug: Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapy |
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: 5 years
Complete response (CR) rate before or at Month 6
Percentage of patients achieving complete response (CR) before or at Month 6
Measured: 4
Secondary outcomes (4)
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: 5 years
Duration of remission (DOR)
DOR will be defined as the duration of the cancer remission
Measured: 5 years
Disease control rate
Disease control rate will be defined as objective response rate + steady disease rate.
Measured: 5 years
Cause of death (COD) when appropriate
Cause of death (COD) when appropriate
Measured: 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2018
- Study start1 Nov 2018
- Primary completion1 Nov 2033 (estimated)
- Study completion1 Nov 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HepatocarcinomaStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Non-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
- Zhenfeng Zhang, MD,PhD, Principal investigator, Second Affiliated Hospital of Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03755739
- Sponsor's protocol ID
- ZZITICI-004
- Status last verified
- Jun 2024
- First submitted
- 3 Nov 2018
- Last updated
- 25 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ou Y, Zhang J, Tan H, He B, Li T, Liu M, Zhi C, Huang J, Li M, Zuo S, Shah NUH, Chen Y, Huang J, Chen D, Qin R, Li X, Lian H, Wu Q, Yang H, Zhang Z. CT-guided intratumoral immunotherapy for advanced solid tumors: a prospective clinical study of safety and systemic antitumor effects. Front Immunol. 2026 Jul 24;17:1869154. doi: 10.3389/fimmu.2026.1869154. eCollection 2026.
PubMed 42568612Tan H, Shah NUH, He B, Liu T, Li T, Liu M, Gu Y, Zhi C, Ou Y, Huang J, Li M, Zuo S, Chen D, Qin R, Yang H, Li X, Lian H, Wu Q, Leidner R, Chen R, Yang A, Yang L, Zhang Z. Intratumoral delivery of PD-1/PD-L1 and CTLA-4 inhibitors for recurrent/refractory solid tumors: a proof-of-concept treatment strategy. Front Immunol. 2025 Dec 12;16:1669924. doi: 10.3389/fimmu.2025.1669924. eCollection 2025.
PubMed 41459523
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II/III Trial of Comparison of Benefit of Administration of Checkpoint Inhibitors Plus Chemodrug Via Artery or Fine Needle to Tumor Versus Vein for Immunotherapy of Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03755739
- Acronym / sponsor ID
- ZZITICI-004
- Conditions
- Hepatocarcinoma, Lung Cancer, Melanoma, Renal Cancer, Head and Neck Cancer, Pancreas Cancer
- Keywords
- Solid cancers, Check-point inhibitors, Interventional Radiology, Trans-artery infusion, Intra-tumor injection
- Phase
- Phase 2/3
- 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 Nov 2018 (actual)
- Primary completion
- 1 Nov 2033 (estimated)
- Study completion
- 1 Nov 2036 (estimated)
- First posted
- 28 Nov 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.
This trial was designed to investigate the safety, response rates and survival outcomes of patients with advanced solid tumors by trans-artery/intra-tumor infusion of PD1/PDL1 antibody and/or CTLA4 antibody ipilimumab plus chemotherapeutic drug and to compare their differences.
Detailed description
Malignant solid tumors including lung and liver cancers are the most common malignancy worldwide, and their mortality rates are very high. China has a huge population base, with about 4,000,000 new cases each year. More than 60% of the solid tumors in China are diagnosed at mid-to-late stage and have lost the chance of surgery. Recently a lot of therapeutic strategies have been developed and applied to clinic including targeted therapy and immunotherapy, but the overall efficiency is still low. It is difficult to be widely used in patients with advanced solid cancers, and more alternative therapies are urgently needed.
Antibodies against PD1, PDL1 and CTLA4 are representative drugs for the check-points inhibitory agents, and their clinical indications have been approved in various types of tumors, including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, and classical Hodgkin's lymphoma and late recurrent head and neck squamous cell carcinoma patients, et al. Those drugs are regularly systemically administrated by vein infusion, however, local delivery of those drugs via interventional radiology technique including trans-artery or intra-tumor injection may increase the local drug concentration in the tumor, improve the efficacy, and reduce systemic adverse reactions, through so called "first pass effect" of drug on target organs. To the investigator's knowledge, no studies have been developed on the efficacy and survival benefit of localized delivery of checkpoint inhibitors for treatment of cancer patients. This phase II-III clinical trial was designed to compare the effects of Pembrolizumab, Tecentriq, et al and/or ipilimumab plus chemotherapeutic drug such as doxorubicin on the survival benefit of patients with advanced solid cancers, including ORR, DCR, median survival time, and safety.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab via localized infusion | Experimental | Drug: Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapyThis group dividied into two subgroups: 1. Checkpoint inhibitor (CPI) such as Pembrolizumab ± Ipilimumab is administrated with a dose of 1-2mg/kg via sustained (10min) micro-pump infusion via artery, plus chemotherapy, every 3 weeks. 2. Checkpoint inhibitor (CPI) such as Pembrolizumab ± Ipilimumab is administrated with a total dose of 150mg via intra-tumor fine needle injection in 5 min, plus doxorubicin, every 3 weeks. |
| Checkpoint inhibitor (CPI) Pembrolizumab plus chemotherapy via vein infusion | Active comparator | Drug: Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapyCheckpoint inhibitor (CPI) such as Pembrolizumab is administrated with a total dose of 2mg/kg via vein infusion (30 min), plus chemotherpy every 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Cytohistological confirmation is required for diagnosis of cancer.
- Signed informed consent before recruiting.
- Age above 18 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 (12 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 |
|---|---|---|
| Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapyAlso: Checkpoint inhibitor (CPI) such as Keytruda plus chemotherapyvein, artery, or intra-tumor infusion of checkpoint inhibitor (CPI) such as Pembrolizumab and/or Ipilimumab, plus chemotherapy to destroy cancer cells and release tumor antigen for improving CPI therapeutic efficacy. | Drug | Checkpoint inhibitor (CPI) Pembrolizumab plus chemotherapy via vein infusion, Pembrolizumab via localized infusion |
Primary outcome
Overall survival
Time frame: 5 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.
Complete response (CR) rate before or at Month 6
Time frame: 4
Percentage of patients achieving complete response (CR) before or at Month 6
4 secondary outcomes
Progression-free survival
Time frame: 5 years
Duration of remission (DOR)
Time frame: 5 years
Disease control rate
Time frame: 5 years
Cause of death (COD) when appropriate
Time frame: 5
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 25 Jun 2024.
- Derived from this study: PubMed 42568612Ou Y, Zhang J, Tan H, He B, Li T, Liu M, Zhi C, Huang J, Li M, Zuo S, Shah NUH, Chen Y, Huang J, Chen D, Qin R, Li X, Lian H, Wu Q, Yang H, Zhang Z. CT-guided intratumoral immunotherapy for advanced solid tumors: a prospective clinical study of safety and systemic antitumor effects. Front Immunol. 2026 Jul 24;17:1869154. doi: 10.3389/fimmu.2026.1869154. eCollection 2026.
- Derived from this study: PubMed 41459523Tan H, Shah NUH, He B, Liu T, Li T, Liu M, Gu Y, Zhi C, Ou Y, Huang J, Li M, Zuo S, Chen D, Qin R, Yang H, Li X, Lian H, Wu Q, Leidner R, Chen R, Yang A, Yang L, Zhang Z. Intratumoral delivery of PD-1/PD-L1 and CTLA-4 inhibitors for recurrent/refractory solid tumors: a proof-of-concept treatment strategy. Front Immunol. 2025 Dec 12;16:1669924. doi: 10.3389/fimmu.2025.1669924. eCollection 2025.
- Individual participant dataSharing planned: No
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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.
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 2/3 study testing Checkpoint inhibitor (CPI) such as Pembrolizumab plus chemotherapy in people with Hepatocarcinoma and Lung 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 9 inclusion and 12 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 25 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Zhenfeng Zhang, MD,PhD (02034153532, zhangzhf@gzhmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03755739, which also lists 2 linked publications.
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 25 Jun 2024.