Clinical Trials

Overview

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 specifically designed for FLC

Study status: Active, recruiting

This phase I clinical trial is now recruiting subjects at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, MD. The study will test the safety and effectiveness the experimental prodrug DRP-104 in combination with an immune checkpoint inhibitor for patients with advanced stage FLC. DRP-104 is an inactive compound that is converted into a broad-acting glutamine antagonist within tumors, while mostly remaining inactivated in other healthy tissues. This study will test the hypothesis that blocking FLC’s glutamine metabolism can directly cause the death of FLC cancer cells, and also enhance a patient’s own anti-cancer immune response. (Click here to learn more about exploiting FLC’s potential metabolic weaknesses.)

While enrollment in this trial is currently open only to FLC patients 18 years old or older, enrollment should soon be open to FLC patients 12 years old and older. For more information about this study, please visit clinicaltrials.gov (NCT06027086) or contact the clinical trials team at Johns Hopkins at GIClinicalTrials@jhmi.edu.

In the video below, Dr. Marina Baretti and Dr. Mark Yarchoan of Johns Hopkins discuss the  pre-clinical work that provided the scientific rationale for the effort, as well as the design and enrollment criteria for the study:


Trial contact information:

Study status: Active, recruiting

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: https://www.clinicaltrials.gov/study/NCT04248569.

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:

Study status: Active, recruiting

This phase I clinical trial will evaluate the immunogenicity, safety, and first efficacy of a DNAJB1-PRKACA fusion transcript-based peptide vaccine (Fusion-VAC-XS15) delivered in combination with the immune checkpoint inhibitor Atezolizumab (TecentriqTM). The study is expected to enroll 20 patients with fibrolamellar carcinoma or other cancers carrying the DNAJB1-PRKACA fusion transcript. It is being conducted by the network of Centers for Personalized Medicine (ZPM) at the University Hospitals of Freiburg, Heidelberg, Tübingen and Ulm in Baden-Württemberg, Germany. The initial Tübingen site is now open.

These researchers are looking into the viability of using a peptide immunization to give a patient’s immune system the ability to identify and destroy “foreign” FLC cells. The peptide vaccine, made from a fragment of the fusion region of FLC’s DNAJB1-PRKACA fusion protein, is being manufactured at the University Hospital Tübingen.

Enrollment in this trial is open to patients 18 years old and older whose disease has the confirmed presence of the DNAJB1-PRKACA fusion transcript.

Participants will be required to visit the Tübingen study center once prior to beginning treatment. Blood will be drawn at the preliminary examination, and research participation eligibility will be determined. The Fusion-VAC-XS15 peptide vaccine will be administered to research participants at least twice during the course of the investigation. In addition, atezolizumab will be given intravenously as an infusion every four weeks. The course of treatment is set over one year.

Details about the study can be found on the University Hospital Tübingen web site (click here for a summary of the study in English) and at https://clinicaltrials.gov/study/NCT05937295. In addition, this linked article, published in Frontiers in Oncology in March 2024 provides more information about the study protocol.

Dr. Juliane Walz, an investigator for this trial, discusses the goals, rationale, design, and eligibility criteria for this clinical study in the video below:


Trial contact information:

Study status: Pending, opening soon

This phase I/II clinical trial will evaluate the safety, side effects, and optimal dosage of DT2216 combined with irinotecan, as well as its effectiveness in treating children, adolescents, and young adults with relapsed (returned after improvement) or refractory (non-responsive to prior treatment) FLC. DT2216 is a targeted protein degrader that inhibits BCL-XL, an anti-apoptotic protein essential for tumor cell survival, potentially stopping tumor growth. Irinotecan, a topoisomerase I inhibitor, disrupts cell division and DNA repair, which may lead to tumor cell death.

The clinical trial is based on research led by Sandy Simon, PhD of Rockefeller University that showed that FLC cells are sensitive to irinotecan, but that sensitivity is inversely correlated with the cells’ expression of BCL-XL.

DT2216 is an investigational drug developed by Dialectic Therapeutics that avoids a complication found with conventional BCL-XL inhibitors – impaired blood clotting caused by a drop in the number of platelets, which are rich in BCL-XL. Dialectic Therapeutics has previously completed a Phase 1 first-in-human study of DT2216 in patients with various cancers. This trial established DT2216’s safety and tolerability, and it confirmed that the drug does not cause thrombocytopenia (low platelet count). The initial trial also established a phase 2 dose for the single agent, and it laid solid groundwork for this study of DT2216 in combination with irinotecan.

The initial Phase 1 portion of this study will be carried out in patients between ages 1 and 21 years with recurrent and/or treatment-refractory solid tumors. This phase will include FLC patients; however, many subjects may have other cancers. Its main goal will be to determine a recommended Phase 2 dose of DT2216, administered in combination with a standard dose of irinotecan. The study also will assess the pharmacokinetics of DT2216 (how the drug is absorbed, distributed, chemically altered, and excreted by the body), and its toxicities. Finally, this component of the study will assess, to the extent possible, the anti-tumor activity of DT2216 in combination with irinotecan in patients with solid tumors, including any patients with FLC. Between 6 and 24 evaluable patients will be required to complete the dose escalation portion of the study.

The Phase 2 portion of the study will be carried out exclusively in FLC patients up to 39 years old. DT2216 will be administered at the recommended dose established in Phase 1, together with irinotecan at its standard dose. Its main goal will be to define anti-tumor activity of the DT2216/irinotecan combination in FLC patients. Between 8 and 15 patients will be enrolled in this phase.

Trial contact information:


Other clinical trials open to fibrolamellar patients

Study status: Active, recruiting

This phase 1, multicenter study is open to patients with metastatic or locally advanced solid tumors and will 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: https://clinicaltrials.gov/study/NCT03860272

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

Study status: Active, recruiting

This phase I/II study is designed to learn more about personalized cancer therapy, the practice of making decisions about what kind of treatment patients should receive based on the specific characteristics of their tumor. The study will evaluate the feasibility of using molecular profile-based evidence to determine individualized cancer therapy for patients with aggressive malignancies. This is a non-randomized trial.

If not already performed, enrolled patients will have the molecular profiles of their tumor tissues/blood assessed. Based on “multi-omic” profiling, a matched therapy, if available, will be recommended by the study’s Molecular Tumor Board.

The principal Investigators for the effort are Ben George, MD and Razelle Kurzrock, MD of the Medical College of Wisconsin.

For more information and the details, visit: https://clinicaltrials.gov/study/NCT05674825

Trial contact information:

  • MCW Clinical Trials Office – 414-805-8900

Study status: Active, not recruiting

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:  https://clinicaltrials.gov/study/NCT03533582

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:

Study status: Active, recruiting

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:  https://clinicaltrials.gov/study/NCT04134559

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:

Please visit clinicaltrials.gov 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.