Carcinoma, HepatocellularPhase 2NCT03939975
Anti-PD-1therapy Combined With Thermal Ablation for Advanced HCC
A Phase 2 study testing pembrolizumab or nivolumab or JS001 in people with Carcinoma, Hepatocellular, run by Sun Yat-sen University at 1 site in China.
Trial summary
The inhibition of programmed cell death protein 1 (PD-1) has shown promising antitumor activity in advanced hepatocellular carcinoma (HCC). Unfortunately, less than 20% of HCC have response. The effect of PD-1 blockade and incomplete thermal ablation in patients with advanced HCC is not yet clearly understood. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- pembrolizumab or nivolumab or JS001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2019to 31 Jul 2019
- Phase
- Phase 2
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eligible patients had pathological diagnosis of HCC by either surgical resection tissue or core needle biopsy; and had advanced stage of disease that is refractory to or is with unacceptable toxicity of sorafenib. Other eligibility criteria included: Child-Pugh A or B7 classification; Eastern Cooperative Oncology Group-performance status score 0-2; adequate bone marrow (leukocyte count >3.0 ×109/L, hemoglobin >8.0 g/L, and platelet count >60 ×109/L), liver (alanine aminotransferase and aspartate aminotransferase <200 IU/mL), renal (creatinine <1.5 times the upper limit of the normal range) and coagulation (international normalized ratio <2.3) function.
Who cannot join
- Exclusion criteria included a history of treatment with immune checkpoint inhibitors, allergies to immunetherapeutics, systemic immunosuppressive therapy, and ongoing or active infection, or an active autoimmune disease.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective Study of Anti-PD-1 Inhibitors Therapy in Combination With Incomplete Thermal Ablation in Patients With Advanced Hepatocellular Carcinoma
The inhibition of programmed cell death protein 1 (PD-1) has shown promising antitumor activity in advanced hepatocellular carcinoma (HCC). Unfortunately, less than 20% of HCC have response. The effect of PD-1 blockade and incomplete thermal ablation in patients with advanced HCC is not yet clearly understood. This study aimed to analyze outcomes of advanced HCC treated with anti PD-1 inhibitors in combination with incomplete thermal ablation.
Read the detailed description
Hepatocellular carcinoma (HCC) is ranked as the third leading cause of cancer death both worldwide and in the China. In the past decade, survivals of patients with advanced HCC or those who have progressed diseases following locoregional treatments can be increased with the multi-kinase inhibitor sorafenib, the first evidence identified drug for HCC. Recent clinical trials further verified some novel tyrosine kinase inhibitors such as regorafenib and cabozantinib, and two programmed cell death protein-1 (PD-1) immune checkpoint inhibitors (ICIs), nivolumab and pembrolizumab, as useful therapies in second line setting following sorafenib.
Advances in programmed cell death protein 1 (PD-1) blockade have shown an ORR of 15-17% and median survival time of 12.9-15.0 months among patients with advanced HCC. Of these, nivolumab and pembrolizumab have been accelerated approved as second-line treatment of advanced HCC. Notably, patients who have tumor responses maintain long-lasting disease control for 9.9-17months and still a large proportion of patients (81-83%) do not respond to mono PD-1 blockade, which emphasizing the need to explore strategies to increase the efficacy of immunotherapy.
An approach to expanding the benefit of ICIs may involve combinations with locoregional therapy like radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), such treatments have been shown to boost tumor-specific T-cell response through release of TAAs from HCC cells. The intent-to-treat population of this study was a subset of patients receiving ongoing ICIs therapy for advanced HCC and is with stable disease or atypical responses in different lesions of the same individuals.
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- pembrolizumab or nivolumab or JS001
- Keywords
- Hepatocellular carcinoma, Immunotherapy, Nivolumab, Pembrolizumab, Radiofrequency Ablation, Microwave ablation
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pembrolizumab or nivolumab or JS001Drug
Also called computed tomography guided radiofrequency ablation, or computed tomography guided microwave ablation
ICIs therapy of nivolumab (3 mg/kg, per 2 weeks) or pembrolizumab (2 mg/kg, per 3 weeks) or JS001 (240mg, per 3 weeks) was performed until the off-treatment criteria were met. For participants with stable disease or atypical progression to ICIs therapy, thermal ablation of radiofrequency ablation or microwave ablation was performed addtionally.
| Study group | Role | What they receive |
|---|---|---|
| Study arm | Experimental | Patients with stable diseases or atypical progression to ICIs monotherapy would be additionally treated with incomplete thermal ablation along with ICIs therapy; and for those who with no lesions eligible for Incomplete ablation, ICIs would be given solely.
Others with complete or partial responses would keep on going with mono-ICIs therapy. Receives: Drug: pembrolizumab or nivolumab or JS001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Safety evaluation was done continuously during ICIs treatment and up to 30 days after the last dose by using the Common Terminology Criteria for Adverse Events (CTCAE; version 4.03). Complications related to ablation procedure were assessed peri-operation period and reported according to the standardized Society of Interventional Radiology grading system.
Measured: 6-8 weeks
Response
Efficacy included objective response (includes complete and partial response), duration of response, and disease control (Includes complete and partial response, stable disease and atypical progression for at least 3 months).
Measured: 6-8 weeks
Secondary outcomes (3)
Time to tumor progression
time from first dose of ICIs drug until the first typical progression of disease
Measured: 3-4 months
Progression-free survival
time from first day of ICIs treatment to first typical disease progression, or death, which occurred earlier
Measured: 3-4 months
Overall survival
time from first study treatment to death of any cause
Measured: 3-4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2019
- Study start1 Jun 2019
- Primary completion31 Jul 2019
- Study completion31 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen 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
- Not applicable
- Intervention model
- Single group
- Model description
- The study subjects were those who with advanced HCC that progressed on first-line sorafenib and treated with anti-PD-1 therapy in combination with incomplete thermal ablation.
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ming Zhao, Sun Yat-sen University
- Investigators
- Ming Zhao, MD, Ph.D, Principal investigator, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03939975
- Sponsor's protocol ID
- B2018-151-01
- Status last verified
- Aug 2019
- First submitted
- 7 Apr 2019
- Last updated
- 19 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lyu N, Kong Y, Li X, Mu L, Deng H, Chen H, He M, Lai J, Li J, Tang H, Lin Y, Zhao M. Ablation Reboots the Response in Advanced Hepatocellular Carcinoma With Stable or Atypical Response During PD-1 Therapy: A Proof-of-Concept Study. Front Oncol. 2020 Oct 9;10:580241. doi: 10.3389/fonc.2020.580241. eCollection 2020.
PubMed 33163408
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Study of Anti-PD-1 Inhibitors Therapy in Combination With Incomplete Thermal Ablation in Patients With Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT03939975
- Acronym / sponsor ID
- B2018-151-01
- Conditions
- Carcinoma, Hepatocellular
- Keywords
- Hepatocellular carcinoma, Immunotherapy, Nivolumab, Pembrolizumab, Radiofrequency Ablation, Microwave ablation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Jun 2019 (actual)
- Primary completion
- 31 Jul 2019 (actual)
- Study completion
- 31 Jul 2019 (actual)
- First posted
- 7 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.
The inhibition of programmed cell death protein 1 (PD-1) has shown promising antitumor activity in advanced hepatocellular carcinoma (HCC). Unfortunately, less than 20% of HCC have response. The effect of PD-1 blockade and incomplete thermal ablation in patients with advanced HCC is not yet clearly understood. This study aimed to analyze outcomes of advanced HCC treated with anti PD-1 inhibitors in combination with incomplete thermal ablation.
Detailed description
Hepatocellular carcinoma (HCC) is ranked as the third leading cause of cancer death both worldwide and in the China. In the past decade, survivals of patients with advanced HCC or those who have progressed diseases following locoregional treatments can be increased with the multi-kinase inhibitor sorafenib, the first evidence identified drug for HCC. Recent clinical trials further verified some novel tyrosine kinase inhibitors such as regorafenib and cabozantinib, and two programmed cell death protein-1 (PD-1) immune checkpoint inhibitors (ICIs), nivolumab and pembrolizumab, as useful therapies in second line setting following sorafenib.
Advances in programmed cell death protein 1 (PD-1) blockade have shown an ORR of 15-17% and median survival time of 12.9-15.0 months among patients with advanced HCC. Of these, nivolumab and pembrolizumab have been accelerated approved as second-line treatment of advanced HCC. Notably, patients who have tumor responses maintain long-lasting disease control for 9.9-17months and still a large proportion of patients (81-83%) do not respond to mono PD-1 blockade, which emphasizing the need to explore strategies to increase the efficacy of immunotherapy.
An approach to expanding the benefit of ICIs may involve combinations with locoregional therapy like radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), such treatments have been shown to boost tumor-specific T-cell response through release of TAAs from HCC cells. The intent-to-treat population of this study was a subset of patients receiving ongoing ICIs therapy for advanced HCC and is with stable disease or atypical responses in different lesions of the same individuals.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study subjects were those who with advanced HCC that progressed on first-line sorafenib and treated with anti-PD-1 therapy in combination with incomplete thermal ablation.
| Arm | Type | Receives |
|---|---|---|
| Study arm | Experimental | Drug: pembrolizumab or nivolumab or JS001Patients with stable diseases or atypical progression to ICIs monotherapy would be additionally treated with incomplete thermal ablation along with ICIs therapy; and for those who with no lesions eligible for Incomplete ablation, ICIs would be given solely. Others with complete or partial responses would keep on going with mono-ICIs therapy. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Eligible patients had pathological diagnosis of HCC by either surgical resection tissue or core needle biopsy; and had advanced stage of disease that is refractory to or is with unacceptable toxicity of sorafenib. Other eligibility criteria included: Child-Pugh A or B7 classification; Eastern Cooperative Oncology Group-performance status score 0-2; adequate bone marrow (leukocyte count >3.0 ×109/L, hemoglobin >8.0 g/L, and platelet count >60 ×109/L), liver (alanine aminotransferase and aspartate aminotransferase <200 IU/mL), renal (creatinine <1.5 times the upper limit of the normal range) and coagulation (international normalized ratio <2.3) function.
Key exclusion criteria (1 listed)
- Exclusion criteria included a history of treatment with immune checkpoint inhibitors, allergies to immunetherapeutics, systemic immunosuppressive therapy, and ongoing or active infection, or an active autoimmune disease.
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 |
|---|---|---|
| pembrolizumab or nivolumab or JS001Also: computed tomography guided radiofrequency ablation, or computed tomography guided microwave ablationICIs therapy of nivolumab (3 mg/kg, per 2 weeks) or pembrolizumab (2 mg/kg, per 3 weeks) or JS001 (240mg, per 3 weeks) was performed until the off-treatment criteria were met. For participants with stable disease or atypical progression to ICIs therapy, thermal ablation of radiofrequency ablation or microwave ablation was performed addtionally. | Drug | Study arm |
Primary outcome
Adverse events
Time frame: 6-8 weeks
Safety evaluation was done continuously during ICIs treatment and up to 30 days after the last dose by using the Common Terminology Criteria for Adverse Events (CTCAE; version 4.03). Complications related to ablation procedure were assessed peri-operation period and reported according to the standardized Society of Interventional Radiology grading system.
Response
Time frame: 6-8 weeks
Efficacy included objective response (includes complete and partial response), duration of response, and disease control (Includes complete and partial response, stable disease and atypical progression for at least 3 months).
3 secondary outcomes
Time to tumor progression
Time frame: 3-4 months
Progression-free survival
Time frame: 3-4 months
Overall survival
Time frame: 3-4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2019.
- Derived from this study: PubMed 33163408Lyu N, Kong Y, Li X, Mu L, Deng H, Chen H, He M, Lai J, Li J, Tang H, Lin Y, Zhao M. Ablation Reboots the Response in Advanced Hepatocellular Carcinoma With Stable or Atypical Response During PD-1 Therapy: A Proof-of-Concept Study. Front Oncol. 2020 Oct 9;10:580241. doi: 10.3389/fonc.2020.580241. eCollection 2020.
- 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. This study is not recruiting at the moment.
Ming Zhao, MD, Ph.D principal investigator
Sun Yat-sen 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 pembrolizumab or nivolumab or JS001 in people with Carcinoma, Hepatocellular, run by Sun Yat-sen 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 1 inclusion and 1 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: finished, as of the sponsor's last update on 19 Aug 2019. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Adverse events (time frame: 6-8 weeks). 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 NCT03939975, which also lists 1 linked publication.
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 19 Aug 2019.