SIRT With Tremelimumab and Durvalumab for Resectable HCC

NCT05701488 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 22-401
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this research study is to evaluate the safety and tolerability of tremelimumab and durvalumab with or without Selective Internal Yttrium-90 Radioembolization (SIRT) in participants with resectable hepatocellular carcinoma (HCC) who will undergo liver surgery. The names of the interventions involved in this study are:

• Durvalumab (a type of immunotherapy)
• Tremelimumab (a type of immunotherapy)
• Selective Internal Yttrium-90 Radioembolization (SIRT) (a type of radiation microsphere bead)

Conditions

Resectable Hepatocellular Carcinoma; Hepatocellular Carcinoma; Hepatocellular Cancer

Keywords

Resectable Hepatocellular Carcinoma; Hepatocellular Carcinoma; Hepatocellular Cancer; Liver Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events

  Defined as All grade 3-5 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms were counted. Rate is the proportion of treated participants experiencing at least one treatment-related grade 3-5 AE of any type during the time of observation.

  up to 18 months

Secondary Outcomes (8)

• Best Radiologic Response

  up to 15 months

• Best Pathological Response

  up to 65 days

• Median Overall Survival (OS)

  up to 3 years

• Median Progression-Free Survival (PFS)

  up to 3 years

• CD8+/CD4+T Cells Level

  up to 3 years

Study Arms (2)

Durvalumab + Tremelimumab (Arm A)

EXPERIMENTAL

-Participants will be randomized into the treatment group in a 1:1 ratio and will receive interventions as outlined: Neoadjuvant Treatment: * Cycle 1: * Day 1 of 28 Day Cycle: Pre-determined dose of Durvalumab and Tremelimumab * Day 28 of 28 Day cycle: Pre-determined dose of Durvalumab * Participants will undergo surgery on day 49 of Cycle 1. Surgery will be performed per institutional standard of care. Adjuvant Treatment: --Cycles 1 (28 days postoperatively) - 13: ---Day 1 of 28 Day Cycle: Pre-determined dose of Durvalumab

Drug: Durvalumab; Drug: Tremelimumab

Durvalumab + Tremelimumab + SIRT (Arm B)

EXPERIMENTAL

-Participants will be randomized into the treatment group in a 1:1 ratio and will receive interventions as outlined: Neoadjuvant Treatment: * Cycle 1: * Day 3 of 28 Day Cycle: Pre-determined dose of Durvalumab and Tremelimumab * Day 31 of 28 Day Cycle: Pre-determined dose of Durvalumab * Day 1 of 28 Day Cycle: Yttrium-90 * Participants will undergo surgery on Day 52 of Cycle 1. Surgery will be performed per institutional standard of care. Adjuvant Treatment: --Cycles 1 (28 days postoperatively) - 13: ---Day 1 of 28 Day Cycle: Pre-determined dose of Durvalumab

Drug: Durvalumab; Drug: Tremelimumab; Device: SIRT

Interventions

Durvalumab DRUG

Intravenous infusion

Also known as: Imjudo, MEDI4736

Durvalumab + Tremelimumab (Arm A); Durvalumab + Tremelimumab + SIRT (Arm B)

Tremelimumab DRUG

Intravenous infusion

Also known as: Imfinzi

Durvalumab + Tremelimumab (Arm A); Durvalumab + Tremelimumab + SIRT (Arm B)

SIRT DEVICE

SIR (Selective Internal Radiation) Sphere resin microspheres, radioactive particles delivered via injection into an artery.

Also known as: Selective Internal Yttrium-90 Radioembolization

Durvalumab + Tremelimumab + SIRT (Arm B)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed HCC (documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable) or clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic subjects (presence of arterial hypervascularity with venous washout). For subjects without cirrhosis, histological confirmation is mandatory.
• Participants must have resectable disease. Those patients must have preserved liver function (Child A) and with either AJCC stage IA, IB, II, and IIIA or BCLC stage 0 or stage A disease. The determination of resectability will ultimately lie in the clinical judgment of the treating investigator and surgical oncologist involved in the care of the patient.
• Participants must be treatment naïve for HCC.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of tremelimumab, durvalumab, and SIRT in participants \<18 years of age, children are excluded from this study.
• Measurable disease per RECIST 1.1 criteria.
• ECOG performance status ≤ 1 (see Appendix A).
• Body weight \>30 kg.
• Participants must have adequate organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dL
• Absolute Neutrophil Count (ANC) ≥ 1,000 /mcL
• Platelets ≥ 80,000 /mcL
• Total Bilirubin ≤ 2.0 mg/dL
• AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional upper limit of normal (ULN)
• Measured Creatinine Clearance \> 40 mL/min by 24-hour urine collection, or
• Calculated Creatinine Clearance (CL) \> 40 mL/min by the Cockcroft-Gault Formula (Cockcroft Gault 1976):

You may not qualify if:

• Participants who have received any prior treatment for HCC.
• Patients who have had a major surgical procedure, open biopsy, or significant traumatic injury with poorly healed wound within 6 weeks prior to first dose of study drug.
• History of allogenic organ transplantation.
• Participants who are receiving any other investigational agents.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients with celiac disease controlled by diet alone
• Patients without active disease in the last 5 years may be included but only after consultation with the sponsor-investigator
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to durvalumab or tremelimumab.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection (including tuberculosis), uncontrolled hypertension (defined as blood pressure of \> 140/90 mmHg during the screening period despite medical management), interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
• Patients who have a primary brain tumor (excluding meningiomas and other benign lesions), any brain metastases, leptomeningeal disease, seizure disorders not controlled with standard medical therapy, or history of a stroke within the year prior to the first dose of study drug.
• History of active primary immunodeficiency.
• Known active infection of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)

Sponsors & Collaborators

• Jiping Wang, MD, PhD: lead
• AstraZeneca: collaborator
• Sirtex Medical: collaborator

Study Sites (3)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

NOT YET RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

durvalumab; tremelimumab

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

Study Officials

• Jiping Wang, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jiping Wang, MD, PhD

CONTACT

617-732-8910; jwang39@partners.org

Anuj Patel, MD

CONTACT

Anuj_Patel@DFCI.HARVARD.EDU

Study Design

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

Study Record Dates

• First Submitted: January 18, 2023
• First Posted: January 27, 2023
• Study Start: April 21, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: September 2, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: BWH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (3)