Neoplasms

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Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Fibrolamellar Carcinoma

Antineoplastic Agents

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Anti-Infective Agents

Nivolumab

Fluorouracil

Interferons

Interferon-alpha

Interferon alpha-2

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Antiviral Agents

Patients receive fluorouracil IV continuously on days 1-7 and 15-21 and recombinant interferon alpha 2b-like protein 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.

Recombinant Interferon Alpha 2b-like Protein

Sunyoung Lee

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.

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.

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

Each tumor will be immuno-profiled using flow cytometry (CyTOF) and immunohistochemistry (IHC). Immune responses, such as infiltration of CD8+/CD4+ T cells and dendritic cells, and cytokine levels in blood, will be compared between pre-treatment and post-treatment via paired t-test and Wilcoxon signed rank test.

Safety will be monitored by addressing and recording all adverse events (AEs), serious adverse events (SAEs) and specific laboratory abnormalities (worst grade). Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.

Overall response rate (ORR) is defined as the number of subjects with the best response of complete response (CR) or partial response (PR) (by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria) divided by the number of subjects who started treatment.

Conversion rate to surgery is defined as the proportion of patients that will be able to receive surgery after the initiation of the study treatment divided by the number of subjects who started treatment. The conversion rate to surgery will be estimated along with the 95% confidence interval (CI).

The Kaplan-Meier method will be used to estimate probability of PFS.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for unresectable fibrolamellar carcinoma