Brief Title
National Translational Science Network of Precision-based Immunotherapy for Primary Liver Cancer
Official Title
A National Translational Science Network of Precision-based Immunotherapy for Primary Liver Cancer (PLC)
Brief Summary
Background:
Primary Liver Cancer is the second most common cause of cancer-related death worldwide. It is
the cancer with the fastest rising incidence and mortality in the United States. Researchers
want to learn more about liver cancer to help them design better treatments.
Objective:
To better understand liver cancer.
Eligibility:
People ages 18 and older who have liver cancer and had or are planning to have immune therapy
Design:
Participants will be screened with a review of their medical records. They will be asked
about their medical history and test results.
Participants will come to the NIH Clinical Center. During this visit, their medical records,
test results, imaging studies, and tissue samples (if available) will be gathered.
Participants will learn the results of a test to see if they have any mutations known to be
connected to cancer. They will learn if there are treatment options for them. Participants
will give blood, urine, and stool samples or rectal swabs.
Participants will not have follow-up visits just for this study. If they join another NIH
research study and have visits for this other study, their medical records; test results; and
blood, urine, and stool samples may be collected. This will occur about every 3 months. If
they have a biopsy or surgery on another study or as part of treatment and there is leftover
tissue, researchers would like to collect some of that tissue.
Participants will be contacted every 6 months by phone or e-mail. They will be asked about
their health. They will provide any medical records, test results, and imaging studies.
Participants will be followed on this study for life.
Detailed Description
Background:
Primary liver cancer (PLC) is the 2nd most common cause of cancer-related death worldwide and
the one cancer with the fastest rising incidence and mortality in the U.S. PLC consists of
two main histological subtypes, i.e., hepatocellular carcinoma (HCC) and cholangiocarcinoma
(CCA), in which diagnoses and treatment decisions are solely based on their baseline clinical
features. However, whether these subtypes are truly distinct or share some fundamental
features which can be pursued to improve clinical management is currently unclear. In
addition, chronic liver diseases, due to complex etiologies such as viral hepatitis, alcohol
consumption, chemicals, parasites or dietary factors, underlie and contribute to liver
damage, increasing the risk of HCC and CCA development and progression. Consequently, PLC is
clinically and biologically heterogeneous which has impeded biological assessment and
clinical treatment.
Despite considerable efforts towards improving diagnosis and development of new treatment
modalities, the improvement of PLC patient survival is minimal. For certain patients at early
or intermediate disease stages, resection and percutaneous local ablation or Transarterial
chemoembolization are available. However, the majority of patients present at advanced stages
of disease, where the current gold standard of treatment is sorafenib, providing only a
minimal improvement in survival time. PLC therefore remains among the most difficult-to-treat
malignancies, with a 5-year survival rate of less than 15% in the United States. Thus, it is
imperative that new treatment modalities are developed to limit cancer development and treat
advanced PLC.
Immunotherapy (IO) is a promising new approach in PLC treatment. Alterations of the immune
system, a component of the revised hallmarks of cancer, is recognized as a central player in
carcinogenesis and cancer progression. Thus, strategies to inhibit or re-direct the immune
response to the presence of tumors are currently being employed or developed.
Immune-checkpoint inhibitors have shown promise in clinical trials of several solid tumors.
Of particular note are monoclonal antibody-based therapy to block immune-inhibitory
molecules, including programmed cell death protein-1 (PD-1), programmed cell death 1 ligand 1
(PDL-1) and cytotoxic T lymphocyte antigen 4 (CTLA4), which block anti-tumor T cell activity.
However, the capacity of these therapies to reduce incidence and progression of PLC are still
relatively unknown. Currently, several trials are underway to study the impact of immune
checkpoint inhibitors as single agents or in combination with targeted therapy, on PLC
development and outcome. Initial findings from Phase I/II clinical trials of PLC are
promising but suggest that only certain patients respond to such treatment regimens while
others do not or suffer from resistance/relapse. At the moment, it is difficult to determine
which patient may benefit from immune therapy, due in large part to the lack of large
comprehensive studies, biobank resources of specimens and biospecimen collection in clinical
trial protocols, which deter our ability to understand and define critical genomic or genetic
factors that contribute to patient response. Hence, we plan to collect PLC patient specimens
and clinical data from those undergoing immunotherapies at NIH Clinical Center and a few
extramural clinical sites to develop predictors for (a) response or resistance to
immunotherapy and (b) acquired resistance to immunotherapy.
Objective:
To establish a biospecimen repository for genomic, genetic and epigenetic analysis to study
the biology of PLC development and progression.
Eligibility:
Patients with histologically/ultrasound/imaging confirmed or suspicious lesions of HCC or
CCA.
Patients with planned or a history of at least 1 dose of immunotherapy for HCC or CCA.
Age >= 18 years old at date of study consent
Design:
This will be a long-term multi-center study to comprehensively study patients with primary
liver cancer (PLC).
Participants will provide clinical information (including medical history, clinical tests,
imaging studies and reports, surgical pathology reports, genetic test results).
Tissue samples, blood, urine and fecal samples will be obtained from participants during this
study.
Broad spectrum of scientific experiments, including genomics, metabolome, microbiome and
immune monitoring will be performed.
Local physicians will be provided with test results of genomics panel evaluation (TruSight
Oncology 500 (TSO-500).
Since long-term follow-up of individuals with PLC is a major feature of the study, local
sites intend to maintain active contact with study subjects for as long as possible. Patients
will be followed throughout the course of their illnesses, with particular attention to
patterns of disease recurrence and progression, response to therapies and duration of
responses. National death index data can also be utilized to obtain patient outcome
information.
Study Type
Observational
Primary Outcome
To establish a biospecimen repository for genomic, genetic and epigenetic analysis to study the biology of PLC development and progression
Secondary Outcome
To estimate overall survival following immunotherapy for PLC
Condition
Hepatocellular Carcinoma
Study Arms / Comparison Groups
1/ Cohort 1
Description: Subjects with a diagnosis or suspicion of PLC
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
500
Start Date
July 28, 2021
Completion Date
December 31, 2025
Primary Completion Date
December 31, 2025
Eligibility Criteria
- INCLUSION CRITERIA:
- Patients with histologically/ultrasound/imaging confirmed or suspicious lesions of HCC
or CCA.
- Patients with planned or a history of at least 1 dose of immunotherapy for HCC or CCA.
- Ability of subject to understand and the willingness to sign a written informed
consent document.
- Age greater than or equal to 18 years old at date of study consent.
EXCLUSION CRITERIA:
- Patients with known HIV infection (as these patients may have abnormal test results which
may confound the endpoints of this study)
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Tim F Greten, M.D., (240) 760-6837, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04145141
Organization ID
200006
Secondary IDs
20-C-0006
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Tim F Greten, M.D., Principal Investigator, National Cancer Institute (NCI)
Verification Date
March 7, 2023