Using Radiotherapy and Immunotherapy to Treat Advanced Liver Cancer Before Transplant

NCT06725121 | Recruiting Phase 1

• 1 other identifier: 24-5402
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to learn if locoregional therapy and immunotherapy can be used together to help patients with hepatocellular carcinoma (HCC) and macrovascular invasion achieve liver transplantation. The main questions it aims to answer are:

• How many patients will achieve transplant with this treatment strategy?
• What will the 5-year survival and recurrence-free survival rates be for these patients? Participants will:
• Undergo a biopsy of the tumor.
• Receive locoregional therapy (SBRT or Y90) followed by immunotherapy (atezolizumab and bevacizumab) 2 to 6 weeks later, for a maximum of 9 months.
• Be referred for a liver transplant and undergo the procedure if deemed eligible and safe.
• If applicable, be followed for five years post-transplant with regular data collection.

Conditions

Hepatocellular Carcinoma (HCC); Macrovascular Invasion; Liver Transplant Surgery; Downstaging

Keywords

SBRT; Y-90; Yittrium-90; Atezolizumab; Bevacizumab; Advanced liver cancer; Radiotherapy; Immunotherapy; Liver cancer; Stereotactic body radiotherapy; Transplant; Liver Transplantation

Outcome Measures

Primary Outcomes (1)

• Evaluate Downstaging Efficacy

  The number of patients who achieve a liver transplant.

  From enrollment to liver transplantation.

Secondary Outcomes (1)

• Long-term Oncological Results

  Form enrollment to 5 years post-transplant.

Study Arms (1)

Treatment

OTHER

This is a pilot, single-arm study enrolling 48 patients to evaluate the feasibility of locoregional therapy followed by immunotherapy in patients with advanced liver cancer. Patients will receive stereotactic body radiotherapy or Yttrium-90 radioembolization as per the standard-of-care (SOC) protocol, determined during Multidisciplinary Rounds. Starting two to six weeks after radiotherapy, patients will begin treatment with Atezolizumab and Bevacizumab administered in approximately 21-day intervals, following SOC procedures, for a maximum of 9 months. Clinical follow-up will align with SOC protocols, and imaging will be performed every 2-3 months during immunotherapy. If a patient is sufficiently responding to treatment at any follow-up, patients will be referred for transplant evaluation and added to the waitlist if no contraindications are found. Patients with disease progression or who become ineligible for LT due to other factors will be transitioned off the study.

Biological: Atezolizumab & Bevacizumab; Drug: Yttrium-90 (Y-90); Radiation: Stereotactic body radiotherapy (SBRT)

Interventions

Atezolizumab & Bevacizumab BIOLOGICAL

Atezolizumab \& Bevacizumab will be initiated as part of the study, as per standard treatment protocol. Administration of Atezolizumab and Bevacizumab will be performed according to SOC in approx. 21-days intervals. Clinical follow up during treatment will be done as per SOC in medical and surgical oncology clinics at UHN.

Also known as: AtezoBev, AVASTIN, TECENTRIQ

Treatment

Yttrium-90 (Y-90) DRUG

Storage, administration and treatment of Y90-RE will be done according to established treatment protocols and standard of care at UHN.

Also known as: YTTRIGA

Treatment

Stereotactic body radiotherapy (SBRT) RADIATION

Dose and administration frequency of SBRT will be done as per current standards for treating HCC at UHN.

Treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-70
• Weight \> 30 kg
• Child Pugh Turcotte score A5 to B7
• Macrovascular invasion (Vp1-3)
• Total tumour volume \< 350 cm3
• Alpha Fetoprotein \< 5000 ng/mL
• No extrahepatic disease
• No other contraindications to undergo a LT
• Eastern Cooperative Oncology Group (ECOG) score 0-1
• Capable to provide inform consent
• Radiological and histological confirmation of hepatocellular carcinoma

You may not qualify if:

• Poorly differentiated HCC
• Prior therapy for hepatocellular carcinoma other than liver resection or ablation
• Portal vein tumor thrombus extending beyond main portal vein
• Obesity class III (BMI ≥ 40 kg/m2)
• Contraindications for radiotherapy (Y90 or SBRT) or AtezoBev

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (2)

London Health Sciences Centre

London, Ontario, N6A 5A5, Canada

NOT YET RECRUITING

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

atezolizumab; Bevacizumab; Yttrium-90; yttrium chloride; Radiosurgery

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Gonzalo Sapisochin, MD, PhD, MSc

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Research Manager

CONTACT

437-772-4354; roxana.bucur@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: LeGresley Chair in Transplant Oncology at UHN, Associate Professor of Surgery Abdominal Transplant & HPB Surgical Oncology

Study Record Dates

• First Submitted: December 5, 2024
• First Posted: December 10, 2024
• Study Start: December 1, 2024
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2034
• Last Updated: December 16, 2024

Record last verified: 2024-12

Locations

CA (2)