Regorafenib and Durvalumab for the Treatment of High-Risk Liver Cancer

NCT05194293 | Active Not Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: ACCRU-GI-1920NCI-2021-12021P30CA015083
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial tests whether regorafenib and durvalumab work to shrink tumors in patients with high-risk liver cancer. Regorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Giving regorafenib and durvalumab may work better in treating patients with high-risk liver cancer.

Conditions

Stage IB Hepatocellular Carcinoma AJCC v8; Stage II Hepatocellular Carcinoma AJCC v8; Stage III Hepatocellular Carcinoma AJCC v8; Stage IIIA Hepatocellular Carcinoma AJCC v8

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) (unconfirmed)

  An objective response is defined as a complete response (CR) or partial response (PR). Disease status will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v).1.1 criteria. ORR is defined as the proportion of evaluable patient who experience a CR or PR divided by the total number of evaluable patients. The final ORR point estimate and corresponding 95% confidence interval will be reported.

  At 16 weeks

Secondary Outcomes (6)

• Rate of surgery during the course of the study

  Up to 10 months

• Incidence of adverse events

  Up to 3 years

• Progression-free survival (PFS)

  3 years

• Overall survival (OS)

  3 years

• Recurrence-free survival (RFS)

  3 years

Other Outcomes (1)

• Immune biomarkers

  Analyze the effect of regorafenib and durvalumab on immune biomarkers in the tumor microenvironment and systemic circulation At baseline, week 8, 12, 20, and at off protocol treatment

Study Arms (1)

Treatment (regorafenib, durvalumab)

EXPERIMENTAL

Patients receive regorafenib PO QD on days 1-21 and durvalumab IV on day 1. Treatment repeats every 28 days for a maximum of 2 years from registration or until decision to proceed to surgery, disease progression, excessive toxicity, or patient withdrawal.

Biological: Durvalumab; Drug: Regorafenib

Interventions

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Treatment (regorafenib, durvalumab)

Regorafenib DRUG

Given PO

Also known as: BAY 73-4506, Regorafenib Anhydrous

Treatment (regorafenib, durvalumab)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years at time of study entry
• Body weight \> 30 kg
• Patients must have hepatocellular carcinoma (HCC) diagnosis confirmed by histology/cytology or clinically by American Association for Study of liver Diseases (AASLD) criteria in cirrhotic patients
• Measurable disease
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Child Pugh class A
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) (obtained =\< 28 days prior to registration)
• Alanine aminotransferase (ALT) =\< 5 x ULN (obtained =\< 28 days prior to registration)
• Aspartate transaminase (AST) =\< 5 x ULN (obtained =\< 28 days prior to registration)
• Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) =\< 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (obtained =\< 28 days prior to registration)
• Creatinine =\< 1.5 x ULN or creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels \> 1.5 x ULN. Creatinine clearance should be calculated per institutional standard (obtained =\< 28 days prior to registration)
• Urinary protein is =\< 1+ on dipstick or routine urinalysis or 24-hour urine demonstrating \< 1 gram of protein (obtained =\< 28 days prior to registration)
• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/Liter (obtained =\< 28 days prior to registration)
• Hemoglobin \>= 9 grams/deciliter (obtained =\< 28 days prior to registration)
• Platelets \>= 75 x 10\^9/Liter (obtained =\< 28 days prior to registration)

You may not qualify if:

• Prior therapy with anti-PD-1, PD L-1 antibody including durvalumab, regorafenib, or other approved systemic therapies for HCC
• Mixed histology HCC or fibrolamellar HCC
• History of upper gastrointestinal bleed =\< 6 months from registration
• Liver directed therapy =\< 28 days prior to registration. Prior liver directed therapy \> 28 days prior to registration is allowed
• Evidence of extrahepatic metastatic disease
• Suitable for liver transplant
• Participation in another clinical study where the patient has received any dose of an investigational product =\< 90 days prior to registration
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Patients with grade \>= 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the study physician
• Any concurrent chemotherapy, investigational product (IP), biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
• Major surgical procedure (as defined by the investigator) =\< 28 days prior to registration
• History of allogenic organ transplantation
• 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

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

durvalumab; Immunoglobulin G; Disulfides; regorafenib

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)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Mehmet Akce

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2021
• First Posted: January 18, 2022
• Study Start: July 1, 2023
• Primary Completion: December 5, 2025
• Study Completion (Estimated): December 5, 2028
• Last Updated: September 4, 2025

Record last verified: 2025-08

Locations

US (3)