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Hepatocellular Carcinoma Non-resectablePhase 1/2NCT03864211

Thermal Ablation Followed by Immunotherapy for HCC

A Phase 1/2 study testing Thermal ablation and Toripalimab in people with Hepatocellular Carcinoma Non-resectable, run by Xiangya Hospital of Central South University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of this study is to determine the safety and efficacy of immunotherapy toripalimab (anti-PD-1 mAb) combined with thermal ablation in patients with Hepatocellular Carcinoma (HCC). Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Hepatocellular Carcinoma Non-resectable
What is being tested?
Thermal ablation and Toripalimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
145 participants
Where
1 siteChina
Study dates
15 Jun 2019to 30 May 2023
Phase
Phase 1/2
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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • With hepatocellular carcinoma, who meet the clinical diagnostic criteria of Primary HCC confirmed by histopathology, cannot undergo radical resection or radical ablation, and fail or intolerable to first-line systemic therapy
  • Be willing and able to provide written informed consent for the trial.
  • Be ≥ 18 years of age on day of signing informed consent.
  • Have ECOG performance status 0-1.
  • Pretreatment CT chest /abdomen /pelvis within 14 days of protocol enrollment.
  • Pathologic diagnosis of hepatocellular carcinoma (including fibrolamellar variants and biphenotypic tumors with a HCC component).
Show all 16Show fewer
  • Child Pugh Class A or B (score =7)
  • Deemed ineligible for curative intent therapy with surgical resection or locoregional treatment or that had progression with at least 3 lesions thereafter.
  • At least one lesion can be completely ablated by radiofrequency/microwave ablation.
  • The the maximum diameter of a single lesion is less than 10 cm. Tumors account for less than 50% of the liver volume.
  • Patients with extrahepatic disease are eligible.
  • Progress or intolerance following at least one systemic treatment regimen.
  • Have measurable disease based on RECIST 1.1.
  • Demonstrate adequate organ function. Adequate Organ Function Laboratory Values System Laboratory Value Hematological Platelets ≥ 50,000 /mL Hepatic Serum total bilirubin ≤ 3 mg/dL AST (SGOT) and ALT (SGPT) ≤ 5 X ULN.
  • Subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 150 days after the last dose of study therapy (for women of child-bearing potential) or 210 days after the last dose of study therapy (for men who have partners of child-bearing potential).
  • Have a life expectancy of greater than 3 months (in the opinion of the treating physician).

Who cannot join

  • Received local ablation or external beam radiation within 3 months .
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a dose of >10 mg prednisone daily or equivalent at time of first dose of trial treatment.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Has a known additional malignancy that is progressing or requires active treatment.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patients with allografts (including liver transplants) are not eligible for this protocol.
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  • Has known history of, or any evidence of active, non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
  • Has received a live vaccine within 30 days of planned start of study therapy.
  • Prior anti-PD-1, anti-PD-L1, anti-PD-L2 or anti-CTLA4 immunotherapy.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Xiangya Hospital, Central South University

    Changsha, Hunan, 410005

Other trials in China

About this study

Official title: Phase I/II Study of Thermal Ablation Followed by Toripalimab in Unresectable Hepatocellular Carcinoma

The purpose of this study is to determine the safety and efficacy of immunotherapy toripalimab (anti-PD-1 mAb) combined with thermal ablation in patients with Hepatocellular Carcinoma (HCC).

Read the detailed description

1.1 Primary Objective \& Hypothesis Determine the safety and efficacy of radiofrequency ablation (RFA)/microwave ablation (MWA) followed by toripalimab for advanced HCC by establishing the rates of toxicity that occur within 6 months after ablation. Hypothesis: Thermal ablation followed by toripalimab will have similar toxicity to toripalimab monotherapy. Thermal ablation enhances antitumor immune response and improves the best overall response rate compared to historical controls with toripalimab alone.

1.2 Secondary Objectives and Hypotheses Estimate the progression-free survival, and overall survival. Hypothesis: Disease control and survival will be better than that observed with toripalimab monotherapy.

1.3 Exploratory Objectives Explore changes in inflammatory biomarkers (including, but not limited to CD8+/Treg ratio, total CD4+ counts, total lymphocyte count) in pretreatment and on-treatment serially collected peripheral blood samples. Hypothesis: Changes in inflammatory biomarkers after thermal ablation may correlate with a more favorable response to immunotherapy.

Being tested
Thermal ablation, Toripalimab
Keywords
Hepatocellular Carcinoma, Immunotherapy, Thermal 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.

  • Thermal ablationProcedure or surgery

    Radiofrequency ablation or microwave ablation is performed under CT or ultrasound guidance for one to five target lesions.

  • ToripalimabDrug

    Also called Immunotherapy

    Protocol 1. Patients received toripalimab (240mg, Q3W) as monotherapy.

    Protocol 2. Patients received toripalimab (240mg, Q3W) on day 3 after ablation.

    Protocol 3. Patients received toripalimab (240mg, Q3W) on day 14 after ablation.

Study groups in NCT03864211
Study groupRoleWhat they receive
Toripalimab monotherapyActive comparatorToripalimab is administrated intravenously (240mg, Q3W) continuously until documented disease progression, discontinuation due to toxicity withdrawal of consent or the study ends.
Receives: Drug: Toripalimab
Thermal ablation plus toripalimabExperimentalOne to five target lesions will be ablated completely. Toripalimab therapy will be initiated on day 3 or day 14 after ablation ((240mg, Q3W) ). Toripalimab is administrated continuously until documented disease progression, discontinuation due to toxicity withdrawal of consent or the study ends.
Receives: Procedure: Thermal ablation; Drug: Toripalimab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival

    From date of randomization until the date of first documented progression or date of death from any cause, whichever comes first.

    Measured: Up to approximately 3 years

Secondary outcomes (8)

  1. Overall response rate

    Treatment evaluation will be done using mRECIST

    Measured: Up to approximately 2 years

  2. Overall survival

    From random date to death for any reason.

    Measured: Up to approximately 3 years

  3. Disease Control Rate

    Defined as the percentage of patients who have achieved complete response, partial response and stable disease

    Measured: Up to approximately 3 years

  4. Number of participants with adverse events

    Evaluation will be done using NCI-CTCAE (version 4.03).

    Measured: Up to approximately 3 years

  5. Tumour marker response

    Percentage of AFP variation

    Measured: Up to approximately 3 years

  6. The time to deterioration of quality of life

    Repetitive decreases of 10 points or more from the baseline of the EORTC QLQ-C30 for two consecutive assessments or a decrease of 10 points or more in a single assessment followed by death from any cause within three weeks.

    Measured: Up to approximately 3 years

  7. Duration of response

    the time from first documented complete or partial response to disease progression or death) according to investigator-assessed and independently-assessed mRECIST criteria

    Measured: Up to approximately 2 years

  8. The general health status

    The Eastern Cooperative Oncology Group (ECOG) was applied to assess the general health status of the patients.

    Measured: Up to approximately3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Mar 2019
  2. Study start15 Jun 2019
  3. Primary completion30 May 2023 (estimated)
  4. Study completion30 May 2023 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
145 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03864211
Sponsor's protocol ID
RI11330
Status last verified
Feb 2022
First submitted
3 Mar 2019
Last updated
29 Sep 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Shi L, Chen L, Wu C, Zhu Y, Xu B, Zheng X, Sun M, Wen W, Dai X, Yang M, Lv Q, Lu B, Jiang J. PD-1 Blockade Boosts Radiofrequency Ablation-Elicited Adaptive Immune Responses against Tumor. Clin Cancer Res. 2016 Mar 1;22(5):1173-1184. doi: 10.1158/1078-0432.CCR-15-1352.

    PubMed 26933175

  • Chu KF, Dupuy DE. Thermal ablation of tumours: biological mechanisms and advances in therapy. Nat Rev Cancer. 2014 Mar;14(3):199-208. doi: 10.1038/nrc3672.

    PubMed 24561446

  • Ulahannan SV, Duffy AG. Hepatocellular carcinoma and immune therapy, from a clinical perspective; where are we? Hepat Oncol. 2016 Aug;3(3):183-185. doi: 10.2217/hep-2016-0008. Epub 2016 Aug 19. No abstract available.

    PubMed 30191038

  • Keam SJ. Toripalimab: First Global Approval. Drugs. 2019 Apr;79(5):573-578. doi: 10.1007/s40265-019-01076-2.

    PubMed 30805896

  • Hwang WL, Pike LRG, Royce TJ, Mahal BA, Loeffler JS. Safety of combining radiotherapy with immune-checkpoint inhibition. Nat Rev Clin Oncol. 2018 Aug;15(8):477-494. doi: 10.1038/s41571-018-0046-7.

    PubMed 29872177

  • Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, Chen L, Pardoll DM, Topalian SL, Anders RA. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014 Oct 1;20(19):5064-74. doi: 10.1158/1078-0432.CCR-13-3271. Epub 2014 Apr 8.

    PubMed 24714771

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Thermal ablation and Toripalimab in people with Hepatocellular Carcinoma Non-resectable, run by Xiangya Hospital of Central South 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 16 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: status not confirmed, as of the sponsor's last update on 29 Sep 2022. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

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?

Progression free survival (time frame: Up to approximately 3 years). 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 NCT03864211, which also lists 6 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 29 Sep 2022.

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