Clinical Trials

Dr. Allison O’Neill and Dr. Mark Yarchoan at FCF’s 2019 Scientific Conference


New medical tests and treatments aren’t offered to the public as soon as they’re discovered. They need to be appropriately studied to determine their safety and effectiveness. Clinical trials are formal research studies to evaluate a medical treatment. Clinical trials can study many things, including:

  • New drugs not yet approved by the U.S. Food and Drug Administration (FDA)
  • New uses of drugs already approved by the FDA
  • New ways to administer drugs, such as in pill form
  • New tests to find and track disease.

According to the National Institutes of Health (NIH), a clinical trial is “a research study in which one or more human subjects are prospectively assigned to one or more interventions to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes.”

If the answers to the following four questions are all yes, a study meets the NIH’s definition of a clinical trial:

  1. Does the study involve human participants?
  2. Are the participants prospectively assigned to an intervention?
  3. Is the study designed to evaluate the effect of the intervention on the participants?
  4. Is the effect being evaluated a health-related biomedical or behavioral outcome?

Types of clinical trials

Clinical trials typically advance through several phases when testing a new treatment:

  • Phase I trials test an experimental treatment on a very small group of people to assess its safety and side effects and to determine appropriate drug dosages.
  • Phase II trials enroll a larger group and focus on determining effectiveness of the treatment for individuals with a certain disease or condition. They also continue to study safety, including short-term side effects.
  • Phase III trials obtain additional information about safety and effectiveness, studying different populations and dosages, often using the drug in combination with other drugs. If the FDA decides that the Phase III results are positive, it will approve the treatment for clinical use.

Participating in a clinical trial

In the United States, over 10,000 clinical trials are held each year. Clinical trials can offer patients access to investigational therapies intended to provide better ways to treat their disease, as well as the opportunity to contribute to medical research. However, they also have associated risks and uncertainties. It’s important to thoroughly understand the purpose, the potential side effects, and possible outcomes of a clinical trial when considering enrollment. If you are interested in participating in a clinical trial, speak with your your doctor who can help you determine which clinical trials may be a good match for you.

Clinician perspectives

In this video segment, Allison O’Neill, M.D., a pediatric medical oncologist, discusses how clinical trials can guide the development of a standard of care for FLC.

In this video, Ghassan Abou-Alfa, M.D., a medical oncologist, discusses the importance of clinical trials for fibrolamellar patients.

Current clinical trials

Study name and description
specifically targeting fibrolamellar
Active, recruiting

DNAJB1-PRKACA Fusion Kinase Peptide Vaccine Combined With Nivolumab and Ipilimumab for Patients With Fibrolamellar Hepatocellular Carcinoma (Baltimore, MD)

This phase I clinical trial of an immune therapy for fibrolamellar carcinoma (FLC) is now recruiting subjects at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, MD. The study asks if individuals can mount an effective immune response against FLC by specifically targeting the unique chimeric protein (resulting from a DNAJB1-PRKACA gene fusion) believed to drive the growth of almost all such tumors. Trial subjects will be given an experimental vaccine (the first patient in the trial received this vaccine on April 21, 2020) containing a peptide (small segment of a protein) that corresponds to the junction region linking the two parts of the chimeric protein. They will simultaneously receive two FDA-approved drugs, Opdivo (nivolumab) and Yervoy (ipilimumab), that may enhance the immune response against FLC by overcoming “checkpoint” systems that can limit the immune system’s ability to fight a cancer.

Enrollment in this trial is open to FLC patients 12 years old and older. The study’s principal investigator is Dr. Mark Yarchoan. More detail can be found at:

Dr. Mark Yarchoan, the principal investigator of this trial, discusses the rationale for the FLC fusion peptide vaccine, the accompanying drug regimen and the eligibility criteria for this first-in-human study in the video below:

Trial contact information:

Anna Ferguson,
Marina Baretti,
Active, not yet recruiting

FusionVAC22_01: Fusion Transcript-based Peptide Vaccine Combined With Immune Checkpoint Inhibition (FusionVAC22) (Tuebingen, Germany)

The aim of this phase I clinical trial is to evaluate the immunogenicity, safety, as well as first efficacy of a DNAJB1-PRKACA fusion transcript-based peptide vaccine (Fusion-VAC-XS15) in combination with the immune checkpoint inhibition Atezolizumab (TecentriqTM). Once opened, the study is expected to enroll 20 patients with fibrolamellar carcinoma or other cancers carrying the DNAJB1-PRKACA fusion transcript.

Enrollment in this trial is open to FLC patients 18 years old and older whose disease has the confirmed presence of the DNAJB1-PRKACA fusion transcript, assessed by RNA-based next-generation sequencing (NGS) or realtime-polymerase chain reaction amplification (RT-PCR).

The study’s principal investigator is Prof. Dr. Helmut Salih at the Clinical Cooperation Unit Translational Immunology, German Cancer Consortium (DKTK). Additional details can be found at:

Trial contact information:

Juliane Walz, Prof.  
Active, recruiting

Nivolumab, Fluorouracil, and Interferon Alpha-2B for the Treatment of Unresectable Fibrolamellar Cancer (Houston, TX)

This new phase I/II trial studies the side effects and how well the combination of nivolumab, fluorouracil, and interferon alpha-2b work for the treatment of fibrolamellar carcinoma (FLC) that cannot be removed by surgery. Immunotherapy with checkpoint inhibitors, 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. Treatment with a combination of nivolumab, fluorouracil, and interferon alpha-2b may work better in treating unresectable fibrolamellar cancer compared to treatment with fluorouracil and interferon alpha-2b alone. This clinical trial stages the drug administration and includes the analysis of “before and after” patient biopsies (samples of tumor tissue) to better understand how the drug combination may affect patients’ immune responses to FLC.

Enrollment in this trial is open to FLC patients 12 years old and older. The study’s principal investigator is Dr. Sunyoung Lee at University of Texas M.D. Anderson Cancer Center. Dr. Ahmed Kaseb at M.D. Anderson Cancer Center is the co-investigator. Additional details can be found at:

Dr. Ahmed Kaseb, an investigator for this study, discusses the design, eligibility criteria and rationale for this trial in the video below:

Trial contact information:

Sunyoung Lee, MD,   
targeting HCC, that include fibrolamellar
Active, recruiting

Cisplatin and Combination Chemotherapy in Treating Children and Young Adults With Hepatoblastoma or Liver Cancer After Surgery (181 study locations)

This phase II/III clinical trial studies how well, in combination with surgery, cisplatin and combination chemotherapy works in treating children and young adults with hepatoblastoma or hepatocellular carcinoma. It is also enrolling patients with fibrolamellar. Because giving combination chemotherapy may kill more tumor cells than one type of chemotherapy alone, this partially randomized study is investigating combinations of drugs that work in different ways to kill tumor cells, including cisplatin, doxorubicin, fluorouracil, vincristine sulfate, carboplatin, etoposide, irinotecan, sorafenib, gemcitabine and oxaliplatin.

The study is also commonly referred to as the “Pediatric Hepatic Malignancy International Therapeutic Trial (PHITT)”. It is sponsored by the Children’s Oncology Group. Enrollment in this study is open to patients up to age 30. The study’s principal investigator is Dr. Gregory M. Tiao of the Cincinnati Children’s Hospital Medical Center. More details and contact information can be found at:

Dr. Allison O’Neill, an investigator involved with the study, discusses the Children’s Oncology Group and the rationale behind this trial in the video below:

Active, recruiting

Checkpoint Inhibition In Pediatric Hepatocellular Carcinoma (Boston, MA)

This phase II clinical trial is studying an immunotherapy drug (pembrolizumab or KEYTRUDA) as a possible treatment for pediatric hepatocellular carcinoma. It is enrolling patients with all types of hepatocellular carcinoma, including fibrolamellar. In this research study, the investigators plan to investigate whether pediatric patients with hepatocellular carcinoma experience stable disease or other response to pembrolizumab.

Enrollment in this study is open to patients up to age 30. The study’s principal investigator is Dr. Allison O’Neill of the Dana-Farber Cancer Institute. More details and contact information can be found at:

Dr. Allison O’Neill, the principal investigator of the trial, discusses key aspects of this study and the role of immunotherapy in FLC treatment in the video segment below:

Trials including a fibrolamellar cohort
Active, recruiting

A Phase 1 Study of AGEN1181, an Fc-Engineered Anti-CTLA-4 Monoclonal Antibody as Monotherapy and in Combination with AGEN2034 (balstilimab), an Anti-PD-1 Monoclonal Antibody, in Subjects with Advanced Cancer (14 study locations)

This is a Phase 1, multicenter study open to patients with metastatic or locally advanced solid tumors to evaluate the safety, tolerability, and pharmacokinetics of an investigational checkpoint inhibitor botensilimab (anti-CTLA-4) alone and in combination with the immune checkpoint inhibitor balstilimab (anti-PD-1). The study is sponsored by Agenus Inc., an immuno-oncology company. Both tested drugs work by blocking proteins that cancer cells use to avoid being seen by the immune system. As a result, the checkpoint inhibitors strive to boost the ability of the immune system to unleash immune responses against the cancer cells.  The study is available at 14 locations throughout the country, including the Memorial Sloan Kettering Cancer Center (MSKCC).

Within the overall study, a new fibrolamellar cohort has been established, focused on providing the anti-CTLA-4 checkpoint inhibitor AGEN1181 in combination with the anti-PD-1 checkpoint inhibitor balstilimab.

For more information and the details on the 14 study locations, visit:

Dr. Ghassan Abou-Alfa, the principal investigator for the study at MSKCC, provides an overview of the clinical trial in the video segment below:

Trials potentially open to fibrolamellar patients
Active, recruiting

NCI MATCH Clinical Trial (multiple locations)

The National Cancer Institute has launched a Molecular Analyses for Therapy Choice (MATCH) Clinical Trial, exploring the effectiveness of targeted cancer therapy based on genetic mutation rather than type of cancer. While the study is not testing any drugs known to target the principal genetic mutation involved in fibrolamellar carcinoma, patients may be able to participate if their genetic profile includes a mutation targeted in the study. Please click the link below for details and talk to your doctor to see if this is right for you. Learn More

Please visit for a comprehensive list of active trials. 

The Fibrolamellar Cancer Foundation does not provide medical advice.  We provide website users with information to help them better understand their health conditions and current approaches towards diagnosis, treatment and supportive care. Always seek the advice of your physician or other qualified healthcare provider.