Combining ablation with Tislelizumab for treating recurrent liver cancer

CT-guided Thermal Ablation Plus Tislelizumab Versus Ablation Alone for Intrahepatic Recurrent Early Stage Hepatocellular Carcinoma: a Randomized Controlled Phase II Clinical Trial

This study is testing if combining a treatment that destroys tumors with an immune-boosting drug can help people with early recurrent liver cancer live longer and have fewer recurrences compared to just the tumor treatment alone.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: prednisone, tislelizumab, immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT04663035 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial investigates the effectiveness and safety of combining ablation therapy with Tislelizumab, an immunotherapy agent, compared to ablation alone in patients with early recurrent hepatocellular carcinoma (HCC). The study aims to include patients diagnosed with recurrent HCC who are at high risk of recurrence and randomly assign them to receive either the combination treatment or ablation alone. The primary outcomes will focus on tumor recurrence rates, overall survival, and safety profiles of the treatments. By enhancing immune response through Tislelizumab, the study seeks to improve treatment outcomes for these patients.

Who should consider this trial

Good fit: Ideal candidates are patients with early-stage recurrent hepatocellular carcinoma who meet specific diagnostic criteria and are at high risk of recurrence.

Not a fit: Patients with advanced HCC or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the recurrence rates of hepatocellular carcinoma and improve overall survival for patients.

How similar studies have performed: While the combination of ablation and immunotherapy is a novel approach, similar studies have shown promise in enhancing treatment outcomes for cancer patients.

Eligibility criteria

Inclusion Criteria:

1. Pathological diagnosed HCC.
2. 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.
3. 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.
4. The recurrence time of HCC should be between 3 and 12 months.
5. 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.

6. 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：

1. WBC ≥ 2.0 x 109/L (stable, off any growth factor within 4 weeks of study drug administration)
2. Neutrophils ≥ 1.5 x 109/L (stable, off any growth factor within 4 weeks of study drug administration)
3. Platelets ≥ 60 x 109/L (transfusion to achieve this level is not permitted)
4. Hemoglobin ≥ 80 g/L (may be transfused to meet this requirement)

II. Adequate hepatic function:

1. Serum Aspartate Aminotransferase (AST) \< 8 X ULN
2. Serum Alanine Aminotransferase (ALT) \< 8 X ULN
3. Serum total bilirubin \< 3 mg/dL
4. Serum albumin ≥ 2.8 g/dL

III. Adequate coagulation function:

a)Prothrombin time (PT)-international normalized ratio (INR)≤ 2.3 or PT \< 6 seconds above control

IV. Adequate renal function:

1. Creatinine Crack \>40 mL/min (Cockcroft-Gault formula) a serum creatinine of \< 1.5 × ULN

   Exclusion Criteria:

   -Target lesion

   1. Known fibrolamellar HCC, sarcomatous HCC, or mixed cholangiocarcinoma and HCC.

   2. Patients who have undergone a liver transplant or those who are in the waiting list for liver transplantation.

   3. With vascular invasion and extrahepatic metastases.
   * General condition

     1. 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.

     4. 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.

     8. 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.

     9. Uncontrolled or clinically significant cardiac disease. 10. Positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
   * Previous / concomitant therapy

     1. 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)
     2. Prior organ allograft or allogeneic bone marrow transplantation
     3. 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).
     4. Active bacterial or fungal infections requiring systemic treatment within 7 days
     5. 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
     6. Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

Where this trial is running

Guangzhou, Guangdong

• Department of Minimally Invasive and Interventional Radiology, Liver Cancer Study and Service Group, Sun Yat-sen University Cancer Center, — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Principal investigator: Ming Zhao, MD — Sun Yat-sen University
• Study coordinator: Ming Zhao, MD

Conditions Recurrent Hepatocellular Carcinoma; Ablation; Tislelizumab