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Nivolumab, Fluorouracil, and Interferon Alpha 2B for the Treatment of Unresectable Fibrolamellar Cancer | Clinical Trials | Clareo Health

RECRUITINGPHASE1/PHASE2

Nivolumab, Fluorouracil, and Interferon Alpha 2B for the Treatment of Unresectable Fibrolamellar Cancer

A Phase I/II Study of Nivolumab Plus 5-Fluorouracil Plus Interferon-α2b for Unresectable Fibrolamellar Hepatocellular Carcinoma

NCT04380545•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

Summary

This phase I/II trial studies the side effects and how well nivolumab, fluorouracil, and interferon alpha 2b work for the treatment of fibrolamellar cancer (liver cell cancer) that cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Interferon alpha 2b may help stimulate the immune system to fight cancer. Giving nivolumab, fluorouracil, and interferon alpha 2b may work better in treating unresectable fibrolamellar cancer compared to fluorouracil and interferon alpha 2b alone.

Detailed Description

PRIMARY OBJECTIVE: I. To evaluate the safety and tolerability of therapy with nivolumab + fluorouracil (5-FU) + recombinant interferon alpha 2b-like protein (IFN-alpha2b) in patients with unresectable fibrolamellar hepatocellular carcinoma (FLHCC) in the context of palliative systemic and prebiopsy therapy. SECONDARY OBJECTIVE: I. To assess the efficacy of nivolumab + 5-FU + IFN-alpha2b therapy in patients with unresectable FLHCC by estimating the overall response rate (ORR) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, and comparing those rates to those from historical controls in our published data. EXPLORATORY OBJECTIVES: I. To assess the immunological/biomarker changes in tumor tissues and peripheral blood in response to nivolumab + 5-FU + IFN-aplha2b therapy (pre- versus \[vs\] post-treatment). II. To explore any potential association between these biomarker measures and both antitumor response and immune-related response criteria (irRC) assessed by the University of Texas MD Anderson Cancer Center (MD Anderson) Department of Diagnostic Imaging. OUTLINE: Patients receive fluorouracil intravenously (IV) continuously on days 1-7 and 15-21 and recombinant interferon alpha 2b-like protein subcutaneously (SC) on days 1, 3, 5, 15, 17, and 19. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 3, patients receive nivolumab IV over 30 minutes on day 1, fluorouracil IV continuously on days 1-7 and 15-21, and recombinant interferon alpha 2b-like protein interferon alpha 2b SC on days 1, 3, 5, 15, 17, and 19. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 12 weeks for 6 years.

Eligibility

Age

12 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Patients, or their legal guardian, must give written informed consent prior to initiation of therapy, and patients under age 18 must give assent in keeping with the policies of the institution. Patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy
•Patients with histologically confirmed FLHCC (or with documentation of original biopsy for diagnosis is acceptable if tumor tissue is unavailable). The determination of resectability status will ultimately lie in the clinical judgment of the surgical oncologist and medical oncologist involved in the care of the patient. The definition of resectability is as follows: hepatectomy can achieve a negative margin while preserving more than 30% of the total estimated liver volume, sparing two contiguous hepatic segments, and maintaining vascular inflow, vascular outflow, and biliary drainage. Patients with extrahepatic disease are defined as having unresectable disease
•Patient must have measurable disease defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures \>= 15 mm with conventional techniques or \>= 10 mm with more sensitive techniques such as magnetic resonance imaging (MRI) or spiral computed tomography (CT) scan
•Eastern Cooperative Oncology Group performance status (ECOG PS =\< 1), or for patients under age 18 Karnofsky performance status of \>= 70
•No advanced cirrhosis, with Child-Pugh A
•Absolute neutrophil count (ANC) \>= 1,000 /mm\^3 (within 14 days of the first dose of study drug)
•Platelets \>= 100,000 /mm\^3 (within 14 days of the first dose of study drug)
•Hemoglobin \> 9.0 g/dL (may be transfused or receive epoetin alfa \[e.g., Epogen\] to maintain or exceed this level) (within 14 days of the first dose of study drug)
•Total bilirubin =\< 1.5 mg/dL (within 14 days of the first dose of study drug)
•Serum creatinine =\< 1.5 times the upper limit of normal (ULN) or estimated creatinine clearance (CrCL) \> 40 mL/min (within 14 days of the first dose of study drug)
+22 more criteria

Exclusion Criteria

•Any other malignancy from which the patient has been disease-free for less than 2 years, except for non-melanoma skin cancer, or in situ carcinoma of any site
•Patients who have organ allografts
•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; or have an anticipated need for major surgical procedure during the course of the study (other than defined by protocol). NOTE: Patients will be allowed to start cycle 1 day 1 therapy after 24 hours from pre-treatment biopsy
•Autoimmune disease: patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) are excluded from this study as are patients with a history of autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis \[e.g., Wegener's granulomatosis\])
•Known history of testing positive for human immunodeficiency virus or known acquired immunodeficiency syndrome
•Any underlying medical condition, which in the opinion of the investigator will make the administration of study drug hazardous or will obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea
•Patients who have had a history of acute diverticulitis, abdominal fistula, gastrointestinal perforation, intra-abdominal abscess, gastrointestinal obstruction, or abdominal carcinomatosis which are known risks factors for bowel perforation
•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 stroke within the past year
•History of serious systemic disease, including myocardial infarction or unstable angina within the last 12 months, history of hypertensive crisis or hypertensive encephalopathy, uncontrolled hypertension (blood pressure of \> 140/90 mmHg) at the time of enrollment, New York Heart Association grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (patients with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or significant vascular disease or symptomatic peripheral vascular disease
•Patients who have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications
+16 more criteria

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

January 13, 2021

Primary Completion Date

February 28, 2028

Completion Date

February 28, 2028

Last Updated

March 6, 2026

Enrollment

ESTIMATED participants

Conditions

Stage III Hepatocellular Carcinoma AJCC v8Stage IIIA Hepatocellular Carcinoma AJCC v8Stage IIIB Hepatocellular Carcinoma AJCC v8Stage IV Hepatocellular Carcinoma AJCC v8Stage IVA Hepatocellular Carcinoma AJCC v8Stage IVB Hepatocellular Carcinoma AJCC v8Unresectable Fibrolamellar Carcinoma

Interventions

Fluorouracil

DRUG

Nivolumab

BIOLOGICAL

Recombinant Interferon Alpha 2b-like Protein

BIOLOGICAL

Testing the Addition of an Anti-cancer Drug, Sapanisertib, to the Usual Chemotherapy Treatment (Cabozantinib) in Metastatic Liver Cell Cancer With a Change in Genes for the Protein β-Catenin, The SAPHIRE Trial

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Advanced Hepatocellular CarcinomaMetastatic Hepatocellular Carcinoma+2 more

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ACTIVE_NOT_RECRUITINGPHASE2

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

NCT05194293

Stage IB Hepatocellular Carcinoma AJCC v8Stage II Hepatocellular Carcinoma AJCC v8+2 more

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 6, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Nivolumab, Fluorouracil, and Interferon Alpha 2B for the Treatment of Unresectable Fibrolamellar Cancer

Inclusion Criteria

Exclusion Criteria

Testing the Addition of an Anti-cancer Drug, Sapanisertib, to the Usual Chemotherapy Treatment (Cabozantinib) in Metastatic Liver Cell Cancer With a Change in Genes for the Protein β-Catenin, The SAPHIRE Trial

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

Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study

Zanzalintinib in Second Line and Beyond for the Treatment of Advanced Liver Cancer