Thermal Ablation Followed by Immunotherapy for HCC

NCT03864211 | Unknown Phase 1 DMC

• 1 other identifier: RI11330
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Hepatocellular Carcinoma Non-resectable

Keywords

Hepatocellular Carcinoma; Immunotherapy; Thermal ablation

Outcome Measures

Primary Outcomes (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.

  Up to approximately 3 years

Secondary Outcomes (8)

• Overall response rate

  Up to approximately 2 years

• Overall survival

  Up to approximately 3 years

• Disease Control Rate

  Up to approximately 3 years

• Number of participants with adverse events

  Up to approximately 3 years

• Tumour marker response

  Up to approximately 3 years

Study Arms (2)

Toripalimab monotherapy

ACTIVE COMPARATOR

Toripalimab is administrated intravenously (240mg, Q3W) continuously until documented disease progression, discontinuation due to toxicity withdrawal of consent or the study ends.

Drug: Toripalimab

Thermal ablation plus toripalimab

EXPERIMENTAL

One 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.

Procedure: Thermal ablation; Drug: Toripalimab

Interventions

Thermal ablation PROCEDURE

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

Thermal ablation plus toripalimab

Toripalimab DRUG

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.

Also known as: Immunotherapy

Thermal ablation plus toripalimab; Toripalimab monotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Xiangya Hospital of Central South University: lead

Study Sites (1)

Xiangya Hospital, Central South University

Changsha, Hunan, 410005, China

Location

Related Publications (6)

• 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.

  PMID: 26933175 BACKGROUND

• 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.

  PMID: 24561446 BACKGROUND

• 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.

  PMID: 30191038 BACKGROUND

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

  PMID: 30805896 BACKGROUND

• 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.

  PMID: 29872177 BACKGROUND

• 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.

  PMID: 24714771 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Transurethral Resection of Prostate; toripalimab; Immunotherapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Prostatectomy; Urologic Surgical Procedures, Male; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative; Immunomodulation; Biological Therapy; Therapeutics

Study Officials

• Liangrong Shi, M.D.

  Xiangya Hospital of Central South University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2019
• First Posted: March 6, 2019
• Study Start: June 15, 2019
• Primary Completion: May 30, 2023
• Study Completion: May 30, 2023
• Last Updated: September 29, 2022

Record last verified: 2022-02

Locations

CN (1)