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Stage III Hepatocellular Carcinoma AJCC v8Phase 1/2NCT04380545

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

A Phase 1/2 study testing Fluorouracil, Nivolumab and Recombinant Interferon Alpha 2b-like Protein in people with Stage III Hepatocellular Carcinoma AJCC v8 and Stage IIIA Hepatocellular Carcinoma AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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). Read more about this study

Who is it for?
Ages 12 years and older
What is being tested?
Fluorouracil, Nivolumab and Recombinant Interferon Alpha 2b-like Protein
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
13 Jan 2021to 28 Feb 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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)
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  • 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)
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 5 times institutional ULN (within 14 days of the first dose of study drug)
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study drug
  • Women must not be breastfeeding
  • WOCBP must agree to follow instructions for method(s) of contraception from the time of enrollment for the duration of treatment with study drug(s) plus 5 half-lives of study drug(s) plus 30 days (duration of ovulatory cycle) for a total of 5 months post treatment completion
  • Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug(s) plus 90 days (duration of sperm turnover) for a total of 7 months post-treatment completion
  • Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, WOCBP must still undergo pregnancy testing as described in these sections. Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception, which have a failure rate of < 1% per year when used consistently and correctly. At a minimum, subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective as listed below:
  • HIGHLY EFFECTIVE METHODS OF CONTRACEPTION:
  • Male condoms with spermicide
  • Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants, and intrauterine devices such as Mirena by WOCBP subject or male subject's WOCBP partner
  • Nonhormonal intrauterine devices, such as ParaGard
  • Tubal ligation
  • Vasectomy
  • Complete Abstinence
  • Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs. Abstinence is only acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, profession of abstinence for entry into a clinical trial, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Subjects who choose complete abstinence are not required to use a second method of contraception, but female subjects must continue to have pregnancy tests. Acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence
  • LESS EFFECTIVE METHODS OF CONTRACEPTION:
  • Diaphragm with spermicide
  • Cervical cap with spermicide
  • Vaginal sponge
  • Male condom without spermicide
  • Progestin-only pills by WOCBP subject or male subject's WOCBP partner
  • Female condom
  • A male and female condom must not be used together

Who cannot join

  • 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
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  • 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
  • Patients who have received any live or attenuated viral vaccines within a month prior to initiation of study drugs
  • Patients who have active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test at screening
  • Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody (HBcAb) test and negative HBV deoxyribonucleic acid (DNA) test at screening, are eligible for the study
  • Patients who have active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV ribonucleic acid (RNA) test at screening
  • The HCV RNA test will be performed only for patients who have a positive HCV antibody test
  • Patients who have clinical history of coagulopathy, bleeding diathesis, or thrombosis within the past year
  • Patients who have a serious, non-healing wound, ulcer, or bone fracture
  • Patients who are pregnant (positive pregnancy test) or lactating
  • Patients with prior orthotropic liver transplantation
  • Patients with cirrhosis and severe synthetic liver dysfunction (Child Pugh B-C)
  • Patients must not have received prior anticancer therapy with anti-PD-1 for FLHCC treatment. Patients receiving any concomitant systemic therapy for FLHCC are excluded
  • Patients must not be scheduled to receive another experimental drug while on this study
  • Patients who require ongoing anticoagulation will be excluded. Only aspirin will be permitted. Pre and post-surgical prophylactic anti-coagulation treatment is permitted
  • Patients must not require total parenteral nutrition
  • Patients who are on high dose steroid (e.g. > 10 mg prednisone daily or equivalent) or other more potent immune suppression medications (e.g. infliximab). Corticosteroid use will only be allowed during trial participation for grade 3/4 AEs or hypersensitivity reactions
  • Any patients who cannot be compliant with the appointments required in this protocol must not be enrolled in this study

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Sunyoung Lee, 713-792-2828, SSLee1@mdanderson.org

    Sunyoung Lee

    Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Being tested
Fluorouracil, Nivolumab, Recombinant Interferon Alpha 2b-like Protein
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FluorouracilDrug

    Also called 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione

    Given IV

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

  • Recombinant Interferon Alpha 2b-like ProteinBiological

    Also called Novaferon, Recombinant IFN Alfa-2b-like Protein

    Given SC

Study groups in NCT04380545
Study groupRoleWhat they receive
Treatment (fluorouracil, interferon alpha 2b, nivolumab)ExperimentalPatients 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.
Receives: Drug: Fluorouracil; Biological: Nivolumab; Biological: Recombinant Interferon Alpha 2b-like Protein

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events

    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.

    Measured: Up to 30 days after last treatment dose

Secondary outcomes (3)

  1. Overall response rate (ORR)

    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.

    Measured: 12 weeks after initiation of combined treatment

  2. Conversion rate to surgery

    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).

    Measured: Up to 6 years

  3. Progression-free survival (PFS)

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

    Measured: From the start of treatment to date of patient death (PD), to date of last follow-up if patient is alive without PD, or to date of death, whichever occurs first, assessed up to 6 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 May 2020
  2. Study start13 Jan 2021
  3. Primary completion28 Feb 2028 (estimated)
  4. Study completion28 Feb 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04380545
Sponsor's protocol ID
2019-1135
Other IDs
NCI-2020-02614, 2019-1135
Status last verified
Sep 2026
First submitted
5 May 2020
Last updated
14 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • O'Neill AF, Church AJ, Perez-Atayde AR, Shaikh R, Marcus KJ, Vakili K. Fibrolamellar carcinoma: An entity all its own. Curr Probl Cancer. 2021 Aug;45(4):100770. doi: 10.1016/j.currproblcancer.2021.100770. Epub 2021 Jul 1.

    PubMed 34272087

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Fluorouracil, Nivolumab and Recombinant Interferon Alpha 2b-like Protein in people with Stage III Hepatocellular Carcinoma AJCC v8 and Stage IIIA Hepatocellular Carcinoma AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to 30 days after last treatment dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04380545, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.

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