Regorafenib and Durvalumab for the Treatment of High-Risk Liver Cancer
Liver Cancer / Hepatoblastoma
Unknown Primary
18 Years and older, Male and Female
ACCRU-GI-1920 (primary)
NCI-2021-12021
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.
Objectives
PRIMARY OBJECTIVE:
I. To assess the overall response rate (ORR) at 16 weeks post registration.
SECONDARY OBJECTIVES:
I. To assess the rate of patients who undergo surgery during the course of the study.
II. To assess the safety and tolerability of the combination therapy of regorafenib plus durvalumab.
III. To assess the effect of combination therapy on overall survival.
IV. To assess the effect of combination therapy on progression-free survival (PFS) in patients that do not undergo resection.
V. To assess the effect of combination therapy on recurrent-free survival (RFS) in patients that have resection.
VI. To assess the rate of pathologic complete response.
CORRELATIVE RESEARCH OBJECTIVE:
I. Analyze the effect of regorafenib and durvalumab on immune biomarkers in the tumor microenvironment and systemic circulation.
OUTLINE:
Patients receive regorafenib orally (PO) once daily (QD) on days 1-21 and durvalumab intravenously (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.
After completion of study treatment, patients are followed every 90 days for 3 years.
Eligibility
- 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)
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
- Life expectancy of >= 12 weeks
- Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
* NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Provide informed written consent =< 28 days prior to registration
- Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
* Note: During the active monitoring phase of a study (i.e., active treatment and clinical follow-up), participants must be willing to return to the consenting institution for follow-up
- Willing to provide mandatory tissue specimens and/or blood specimens for correlative research purposes
- Clinical staging T1b/T2 or T3 hepatocellular cancer TNM staging American Joint Committee on Cancer (AJCC) International Union Against Cancer (UICC) 8th edition
* Solitary tumor > 5 cm without vascular invasion
* T2: Solitary tumor > 2 cm with vascular invasion, or multiple tumors, none > 5 cm
* T3: Multiple tumors, at least one of which is > 5 cm
- Able to swallow oral medication
Treatment Sites in Georgia
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