Ablation Plus Tislelizumab Versus Ablation Alone for Intrahepatic Recurrent Early Stage HCC

NCT04663035 | Unknown Phase 2 DMC

• 1 other identifier: B2020-195-01
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, controlled, phase 2 study to assess the efficacy and safety of ablation followed by tislelizumab versus ablation alone in patients with early recurrent hepatocellular carcinoma.

Conditions

Recurrent Hepatocellular Carcinoma

Keywords

Recurrent Hepatocellular Carcinoma; Ablation; Tislelizumab

Outcome Measures

Primary Outcomes (1)

• 1-year recurrence-free survival (RFS) rate

  It is defined as the percentage of patients who achieve a time interval of 1 year of no disease recurrence (i.e., intrahepatic recurrence or extrahepatic metastasis) or death (by any cause) from date of enrollment, whichever occurs first.

  1 year

Secondary Outcomes (7)

• 2-year recurrence-free survival (RFS) rate

  2 years

• 3-year recurrence-free survival (RFS) rate

  3 years

• Overall survival (OS)

  3 years

• Time to Recurrence (TTR)

  From date of randomization up to 5 years, approximately

• Safety of ablation and ablation plus Tislelizumab

  From date of randomization up to 5 years, approximately

Study Arms (2)

Ablation Plus Tislelizumab

EXPERIMENTAL

Patients in this arm will receive ablation followed by tislelizumab, which will be started within 3-7 days after ablation until disease progression or intolerable toxicity, for 12 months.

Drug: Tislelizumab; Procedure: Ablation

Ablation Alone

ACTIVE COMPARATOR

Patients in this group will receive ablation therapy and then enter the follow-up phase.

Procedure: Ablation

Interventions

Tislelizumab DRUG

200mg, iv. drip, Q3W. Tislelizumab will start within 3-7 days after ablation treatment. The longest course of treatment is 12 months.

Also known as: Tislelizumab Injection

Ablation Plus Tislelizumab

Ablation PROCEDURE

After local anesthesia and intravenous sedative injection, the unipolar needle would be gradually inserted into the lesion and placed on the deepest edge of the lesion. The ablation electrode is a unipolar needle with a bare end of 2 or 3 cm (adjusted to tumor size). The ablation power is 150 watts (range from 100 to 200 watts). In general, the average ablation time for each lesion is about 12 minutes (ranging from 10 to 15 minutes).

Ablation Alone; Ablation Plus Tislelizumab

Eligibility Criteria

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

You may qualify if:

• Pathological diagnosed HCC.
• The recurrent lesions should meet the diagnostic and staging criteria of the Barcelona liver cancer clinical system (BCLC) recommended by the American Association of liver Diseases and the European Association of liver Diseases (AASLD/EASL). The specific diagnostic criteria for HCC are as follows:
• I. Intrahepatic lesions ≥ 1cm, with typical HCC findings in dynamic contrast-enhanced CT or MRI, that is, enhancement in arterial phase or decreased enhancement in portal phase.
• II. Intrahepatic lesions ≥ 1cm without typical imaging findings, the biopsy can be performed.
• III. Intrahepatic lesions \< 1cm, ultrasound follow-up every 4 months, if the enlargement exceeds 1cm, then refer to standard I or II.
• If the intrahepatic recurrent lesions are diagnosed by the above criteria, BCLC-0/A stage can be performed as follows:
• I. BCLC-0: single lesion \< 2cm, Child-Pugh A (without ascites), and ECOG-PS 0. II.BCLC-A: single lesion ≥ 2cm, Child-Pugh A (without ascites), and ECOG-PS 0. III.BCLC-A stage: 2-3 lesions but all are less than 3cm. Child-Pugh A (without ascites), and ECOG-PS 0.
• The recurrence time of HCC should be between 3 and 12 months.
• Patients with recurrent HCC lesions should meet the indications of ablation treatment, as follows:
• I. Single lesion ≤ 5 cm; or. II. 2-3 lesions, all are less than 3cm; and. III. The location of the above lesions should be far away from the dangerous sites.
• \. Life expectancy ≥ 12 months. 7. The laboratory test shall be completed within 7 days before the screening and the following criteria shall be met: I. Adequate hematologic function：
• WBC ≥ 2.0 x 109/L (stable, off any growth factor within 4 weeks of study drug administration)
• Neutrophils ≥ 1.5 x 109/L (stable, off any growth factor within 4 weeks of study drug administration)
• Platelets ≥ 60 x 109/L (transfusion to achieve this level is not permitted)
• Hemoglobin ≥ 80 g/L (may be transfused to meet this requirement)

You may not qualify if:

• Target lesion
• \. Known fibrolamellar HCC, sarcomatous HCC, or mixed cholangiocarcinoma and HCC.
• \. Patients who have undergone a liver transplant or those who are in the waiting list for liver transplantation.
• \. With vascular invasion and extrahepatic metastases.
• General condition
• \. Patients with cardiac pacemaker implantation. 2. Any history of hepatic encephalopathy. 3. Any prior (within 1 year) or current clinically significant ascites as measured by physical examination and that requires active paracentesis for control.
• \. Any history of clinically meaningful variceal bleeding within the last 3 months 5. Hepatitis B virus DNA copy number \> 500 IU/mL. 6. Hepatitis D infection in subjects with hepatitis B. 7. Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, prostate cancer without evidence of PSA progression or carcinoma in situ such as the following: gastric, prostate, cervix, colon, melanoma, or breast for example.
• \. Subjects with any active autoimmune disease or history of known or suspected autoimmune disease except for subjects with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• \. Uncontrolled or clinically significant cardiac disease. 10. Positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Previous / concomitant therapy
• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti- CD137, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
• Prior organ allograft or allogeneic bone marrow transplantation
• All toxicities attributed to prior anti-cancer therapy other than neuropathy, alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 5.0) or baseline before administration of study drug. Subjects with toxicities attributed to prior anti-cancer therapy which are not expected to resolve and result in long lasting sequelae are permitted to enroll. Neuropathy must have resolved to Grade 2 (NCI CTCAE version 5.0).
• Active bacterial or fungal infections requiring systemic treatment within 7 days
• Use of other investigational drugs (drugs not marketed for any indication) within 28 days or at least 5 half-lives (whichever is longer) before study drug administration

Sponsors & Collaborators

• Ming Zhao: lead

Study Sites (1)

Department of Minimally Invasive and Interventional Radiology, Liver Cancer Study and Service Group, Sun Yat-sen University Cancer Center,

Guangzhou, Guangdong, 500060, China

RECRUITING

Related Publications (5)

• 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.

  PMID: 33163408 BACKGROUND

• Pan T, Xie QK, Lv N, Li XS, Mu LW, Wu PH, Zhao M. Percutaneous CT-guided Radiofrequency Ablation for Lymph Node Oligometastases from Hepatocellular Carcinoma: A Propensity Score-matching Analysis. Radiology. 2017 Jan;282(1):259-270. doi: 10.1148/radiol.2016151807. Epub 2016 Jul 11.

  PMID: 27399327 BACKGROUND

• Deng H, Kan A, Lyu N, Mu L, Han Y, Liu L, Zhang Y, Duan Y, Liao S, Li S, Xie Q, Gao T, Li Y, Zhang Z, Zhao M. Dual Vascular Endothelial Growth Factor Receptor and Fibroblast Growth Factor Receptor Inhibition Elicits Antitumor Immunity and Enhances Programmed Cell Death-1 Checkpoint Blockade in Hepatocellular Carcinoma. Liver Cancer. 2020 Jun;9(3):338-357. doi: 10.1159/000505695. Epub 2020 Feb 25.

  PMID: 32647635 BACKGROUND

• Lyu N, Kong Y, Pan T, Mu L, Sun X, Li S, Deng H, Lai J, Zhao M. Survival benefits of computed tomography-guided thermal ablation for adrenal metastases from hepatocellular carcinoma. Int J Hyperthermia. 2019;36(1):1003-1011. doi: 10.1080/02656736.2019.1663279.

  PMID: 31544545 BACKGROUND

• Mu L, Pan T, Lyu N, Sun L, Li S, Xie Q, Deng H, Wu P, Liu H, Zhao M. CT-guided percutaneous radiofrequency ablation for lung neoplasms adjacent to the pericardium. Lung Cancer. 2018 Aug;122:25-31. doi: 10.1016/j.lungcan.2018.05.004. Epub 2018 May 12.

  PMID: 30032841 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

tislelizumab

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

Study Officials

• Ming Zhao, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ming Zhao, MD

CONTACT

86-20-87343272; zhaoming@sysucc.org.cn

Ning Lyu, MD

CONTACT

86-020-87343272; lvning@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 9, 2020
• First Posted: December 10, 2020
• Study Start: December 21, 2020
• Primary Completion: December 18, 2023
• Study Completion: December 18, 2025
• Last Updated: March 22, 2023

Record last verified: 2023-03

Locations

CN (1)