Hepatic CancerPhase 2NCT06492408
Neoadjuvant Intra-tumor Double Immunotherapy for Hepatocellular Carcinoma.
A Phase 2 study testing ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab in people with Hepatic Cancer and Surgery, run by Second Affiliated Hospital of Guangzhou Medical University at 1 site in China.
Trial summary
This trial is designed to investigate the safety, response rates and survival outcomes of patients with hepatocellular carcinoma by delivery of CTLA4 and PD1 or PDL1 antibodies combination through CT-guided intra-tumor (IT) injection. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatic Cancer, Surgery
- What is being tested?
- ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteChina
- Study dates
- 1 Jul 2024to 30 Dec 2033
- Phase
- Phase 2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed previously untreated hepatocellular carcinoma (HCC). If a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected HCC are eligible, but pathology must be confirmed prior to initiating treatment on study.
- The patient must be a suitable candidate for surgery, in the opinion of the treating physician.
- Signed and dated written informed consent must be provided by the patient prior to admission to the study in accordance with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation.
- Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L; Hemoglobin >= 8.0 g/dL; Platelets >= 100 x 10^9/L; Total bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert syndrome who can have total bilirubin < 3.0 mg/dL); Creatinine =< 1.5 x ULN or calculated creatinine clearance >= 50 mL/min using Cockcroft-Gault formula for creatinine clearance calculation OR 24-hour urine creatinine clearance >= 50 mL/min.
- 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. A.Impaired clotting test (platelet count < 60000/mm3, prothrombin activity < 50%).
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- 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: Phase II Study of Neoadjuvant CT-Guided Intra-tumor Double Checkpoint Blockades for Untreated Hepatocellular Carcinoma (HCC) Amenable for Surgical Resection
This trial is designed to investigate the safety, response rates and survival outcomes of patients with hepatocellular carcinoma by delivery of CTLA4 and PD1 or PDL1 antibodies combination through CT-guided intra-tumor (IT) injection.
Read the detailed description
Antibodies against CTLA4, PD1 or PDL1 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 of the tumor, improve the efficacy, and reduce systemic adverse reactions. CTLA4 antibody ipilimumab has been widely effectively using to combine with PD1 or PDL1 antibody and this study is to combine ipilimumab and PD1 antibody or PDL1 antibody, so called double checkpoint inhibitors combination therapy, as neoadjuvant therapy for hepatocellular carcinoma (HCC) via intra-tumor admistration. To the investigator's knowledge, no studies have been developed on the safety, efficacy and survival benefit of the double checkpoint inhibitors combination therapy for cancer patients as neoadjuvant treatment via intra-tumor delivery. This phase II clinical trial is designed to assess the safety and survival benefit of ipilimumab and pembrolizumab or durvalumab combination with or without chemodrug or bevacizumab as neoaduvant therapy on patients with HCC, including safety, pCR, mPR, PFS, ORR, DCR, and median survival time.
- Conditions
- Hepatic Cancer, Surgery
- Being tested
- ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab
- Keywords
- Hepatocellular Carcinoma;, Intra-tumor injection, Neoadjuvant therapy, Surgery, Immunotherapy, CTLA4 antibody, PD1 antibody, PDL1 antibody
- Medical subject headings
- Liver Neoplasms, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumabDrug
Also called Other ICIs
This study has 3 subgroups:
Arm 1. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab is administrated with a total dose of 1-2mg/kg via intra-tumor fine needle injection in 10 min, every 3 weeks, total 3-4 times.
Arm 2. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin is administrated via intra-tumor fine needle injection in 15 min, every 3 weeks, total 3-4 times.
Arm 3. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin plus bevacizumab is administrated via intra-tumor fine needle injection in 20 min, every 3 weeks, total 3-4 times.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: IT injection of double ICIs | Experimental | Neoadjuvant therapy: intra-tumor injection of double ICIs only. Receives: Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab |
| Group 2: IT injection of double ICIs and chemodrug | Experimental | Neoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug. Receives: Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab |
| Group 3: IT injection of double ICIs and chemodrug plus bevacizumab | Experimental | Neoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug plus bevacizumab. Receives: Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
pCR rate for the study groups
Pathologic complete response (pCR) is defined as after neoadjuvant therapy, the surgical specimen can not find any residual cancer cells.
Measured: Six months
mPR rate for the study groups
Major pathologic response (MPR) is defined as pathological less than 10% survival cancer cells after tumor resection.
Measured: Six months
Secondary outcomes (4)
Toxicity of the study groups
Toxicity is assessed by the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 4.
Measured: Six months
Response rates to neoadjuvant treatment
Response rates are assessed by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1.
Measured: Six years
Recurrence-free survival
Recurrence-free survival is measured as routine.
Measured: Six years
Overall survival
To correlate major pathologic response with recurrence-free and overall survival.
Measured: Six years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2024
- Study start1 Jul 2024
- Primary completion30 Dec 2028 (estimated)
- Study completion30 Dec 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 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
- NCT06492408
- Sponsor's protocol ID
- ZZ-IT-ICIs-HCC-Neoadjuvant-027
- Status last verified
- Jul 2024
- First submitted
- 2 Jul 2024
- Last updated
- 9 Jul 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Neoadjuvant CT-Guided Intra-tumor Double Checkpoint Blockades for Untreated Hepatocellular Carcinoma (HCC) Amenable for Surgical Resection
- ClinicalTrials.gov ID
- NCT06492408
- Acronym / sponsor ID
- ZZ-IT-ICIs-HCC-Neoadjuvant-027
- Conditions
- Hepatic Cancer, Surgery
- Keywords
- Hepatocellular Carcinoma;, Intra-tumor injection, Neoadjuvant therapy, Surgery, Immunotherapy, CTLA4 antibody, PD1 antibody, PDL1 antibody
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital of Guangzhou Medical UniversityUniversity, hospital or other
- Study start
- 1 Jul 2024 (actual)
- Primary completion
- 30 Dec 2028 (estimated)
- Study completion
- 30 Dec 2033 (estimated)
- First posted
- 9 Jul 2024 (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 is designed to investigate the safety, response rates and survival outcomes of patients with hepatocellular carcinoma by delivery of CTLA4 and PD1 or PDL1 antibodies combination through CT-guided intra-tumor (IT) injection.
Detailed description
Antibodies against CTLA4, PD1 or PDL1 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 of the tumor, improve the efficacy, and reduce systemic adverse reactions. CTLA4 antibody ipilimumab has been widely effectively using to combine with PD1 or PDL1 antibody and this study is to combine ipilimumab and PD1 antibody or PDL1 antibody, so called double checkpoint inhibitors combination therapy, as neoadjuvant therapy for hepatocellular carcinoma (HCC) via intra-tumor admistration. To the investigator's knowledge, no studies have been developed on the safety, efficacy and survival benefit of the double checkpoint inhibitors combination therapy for cancer patients as neoadjuvant treatment via intra-tumor delivery. This phase II clinical trial is designed to assess the safety and survival benefit of ipilimumab and pembrolizumab or durvalumab combination with or without chemodrug or bevacizumab as neoaduvant therapy on patients with HCC, including safety, pCR, mPR, PFS, ORR, DCR, and median survival time.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1: IT injection of double ICIs | Experimental | Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumabNeoadjuvant therapy: intra-tumor injection of double ICIs only. |
| Group 2: IT injection of double ICIs and chemodrug | Experimental | Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumabNeoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug. |
| Group 3: IT injection of double ICIs and chemodrug plus bevacizumab | Experimental | Drug: ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumabNeoadjuvant therapy: intra-tumor injection of double ICIs and chemodrug plus bevacizumab. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Histologically or cytologically confirmed previously untreated hepatocellular carcinoma (HCC). If a diagnostic biopsy is available, a pre-treatment biopsy is not required. Patients with a suspected HCC are eligible, but pathology must be confirmed prior to initiating treatment on study.
- The patient must be a suitable candidate for surgery, in the opinion of the treating physician.
- Signed and dated written informed consent must be provided by the patient prior to admission to the study in accordance with International Conference on Harmonization-Good Clinical Practice (ICH-GCP) guidelines and to the local legislation.
- Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L; Hemoglobin >= 8.0 g/dL; Platelets >= 100 x 10^9/L; Total bilirubin =< 1.5 x upper limit of normal (ULN) (except subjects with Gilbert syndrome who can have total bilirubin < 3.0 mg/dL); Creatinine =< 1.5 x ULN or calculated creatinine clearance >= 50 mL/min using Cockcroft-Gault formula for creatinine clearance calculation OR 24-hour urine creatinine clearance >= 50 mL/min.
Key exclusion criteria (10 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 |
|---|---|---|
| ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumabAlso: Other ICIsThis study has 3 subgroups: Arm 1. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab is administrated with a total dose of 1-2mg/kg via intra-tumor fine needle injection in 10 min, every 3 weeks, total 3-4 times. Arm 2. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin is administrated via intra-tumor fine needle injection in 15 min, every 3 weeks, total 3-4 times. Arm 3. Ipilimumab +pembrolizumab or Ipilimumab +durvalumab combined with idarubicin plus bevacizumab is administrated via intra-tumor fine needle injection in 20 min, every 3 weeks, total 3-4 times. | Drug | Group 1: IT injection of double ICIs, Group 2: IT injection of double ICIs and chemodrug, Group 3: IT injection of double ICIs and chemodrug plus bevacizumab |
Primary outcome
pCR rate for the study groups
Time frame: Six months
Pathologic complete response (pCR) is defined as after neoadjuvant therapy, the surgical specimen can not find any residual cancer cells.
mPR rate for the study groups
Time frame: Six months
Major pathologic response (MPR) is defined as pathological less than 10% survival cancer cells after tumor resection.
4 secondary outcomes
Toxicity of the study groups
Time frame: Six months
Response rates to neoadjuvant treatment
Time frame: Six years
Recurrence-free survival
Time frame: Six years
Overall survival
Time frame: Six 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 9 Jul 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.
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 study testing ipilimumab, pembrolizumab, durvalumab, idarubicin, bevacizumab in people with Hepatic Cancer and Surgery, 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 7 inclusion and 10 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 9 Jul 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 (+862039195966, zhangzhf@gzhmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pCR rate for the study groups (time frame: Six months). 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?
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 9 Jul 2024.