Below are descriptions of the current and completed clinical trials that have been funded by FCF.
Project summaries: Clinical trials
Timeframe: 2021 - 2022
Goal: Assess the potential of the combination of nivolumab, fluorouracil, and interferon alpha-2b as a treatment option for unresectable disease
Principal Investigators: Sunyoung Lee, MD and Ahmed Kaseb, MD, University of Texas M.D. Anderson Cancer Center
This 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.
Timeframe: 2020 - 2022
Goal: Assess potential to induce immune response with a FLC therapeutic vaccine
Principal Investigator: Mark Yarchoan, MD, Associate Professor, Oncology/Division of GI Malignancies, Sidney Kimmel Comprehensive Cancer Center
This clinical trial of an immune therapy for fibrolamellar carcinoma (FLC) is recruiting subjects at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, MD. The study investigates whether 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 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. Details and contact information can be found at: https://www.clinicaltrials.gov/ct2/show/NCT-04248569
Timeframe: 2019-2022
Goal: Assess potential to induce immune response with a FLC therapeutic vaccine
Principal Investigator: Mark Yarchoan, MD, Associate Professor, Oncology/Division of GI Malignancies, Sidney Kimmel Comprehensive Cancer Center
FLC is a rare and often lethal form of liver cancer for which there is no standard treatment option beyond surgery. Immune checkpoint inhibitors are a revolutionary new form of cancer therapy. These drugs “take the brakes off” the immune system, enhancing its ability to fight cancer. Examples of these new medicines include the PD1 inhibitor nivolumab (Opdivo), and the CTLA-4 inhibitor ipilimumab (Yervoy). Many patients with FLC currently receive an immune checkpoint inhibitor off-label. However,clinical experience suggests that they generally do not achieve strong anti-tumor responses from single checkpoint inhibitors. This study seeks to develop immunotherapy approaches to FLC that offer greater clinical benefit.
This project entails the first test in patients of a combination of two checkpoint inhibitors (nivolumab and ipilimumab) plus a new vaccine designed to direct the immune response against FLC by targeting the DNAJ-PKAc fusion protein found in almost every case of this cancer. The fusion protein serves as a neoantigen, an abnormal protein found in the cancer but absent from normal cells. The selective component of the vaccine is a peptide (short segment of a protein) overlapping the junction between the DNAJ and PKAc segments of the fusion protein, which is precise and consistent among FLC tumors. Thus, the vaccine could be harnessed by the immune system to recognize and eliminate cancer cells in any FLC patient with the characteristic gene fusion, in contrast to cancers for which a neoantigen vaccine must be personalized for each individual patient.
The primary goal of the study is to begin assessment of the safety and clinical activity of the FLC-vaccine in combination with nivolumab and ipilimumab in patients for whom complete surgical resection of the cancer is not possible. We also seek to determine if the combination of peptide vaccine and checkpoint inhibitors will promote induction and/or expansion of T cells that specifically recognize the DNAJ-PKAc fusion protein.
Timeframe: 2012 - 2014
Goal: Assess potential of treatment options for FLC
Principal Investigator: Ghassan Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center
FCF funded the first clinical trial of drugs aimed specifically at fibrolamellar liver cancer. The trial was also conducted at other consortium members, including the University of California San Francisco, Johns Hopkins, and Dana Farber. Two major pharmaceutical companies donated the drugs.
Key findings: Estrogen deprivation therapy with letrozole and leuprolide, alone or in combination with the mTOR inhibitor, everolimus, did not demonstrate clinical activity in advanced fibrolamellar carcinoma.
Click here to read the published results of the study.