Trial Title:
FAP PET/CT or PET/MR Production in the Diagnosis, Staging, and Efficacy Assessment of Malignant Tumors Application
NCT ID:
NCT06270394
Condition:
Malignant Tumors
Positron-Emission Tomography
Conditions: Official terms:
Neoplasms
Conditions: Keywords:
FAPI
PET/CT
PET/MRI
Malignant Tumors
Study type:
Interventional
Study phase:
N/A
Overall status:
Suspended
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
68Ga-Fibroblast activation protein inhibitor
Description:
Fibroblast activation protein (FAP), a type II transmembrane serine protease with
dipeptidyl peptidase and endopeptidase activities. FAP is a specific surface marker for
activated fibroblasts in the mesenchyme of tumors, which account for 90% of the stroma of
epithelial neoplasms. FAP inhibitors (FAPIs) can specifically target and bind to FAP.
These inhibitors that are radiolabeled with gallium 68 (68Ga-FAPIs) can be probes for
visualization of the FAP tumor stroma. Previous studies have demonstrated that
68Ga-FAPI-04 is not dependent on blood glucose levels, has an equal or better
tumor-to-background ratio, and clearly visualizes primary tumors and their metastatic
foci. In addition, previous studies on 68Ga-FAPI-04 have focused on PET/CT and the
efficacy of PET/MR with FAPI for postoperative evaluation of GI tumors remains to be
clarified.
Arm group label:
68Ga-FAPI PET/MRI scan
Other name:
PET-MRI (SIGNA PET/MR manufactured by GE Healthcare)
Summary:
This clinical trial aims to investigate the value of fibroblast activation protein
PET/CT(PET/MR) in the diagnosis, staging, and evaluation of treatment outcomes in
malignant tumors. The main question it aims to answer is:
Fibroblast Activation Protein PET/CT(PET/MR) whether or in which cases this assay is
superior to conventional FDG examination in the diagnosis, staging, and assessment of
therapeutic efficacy of malignant tumors, thinking about the reasons behind this.
Investigators will screen suitable participants among patients undergoing routine FDG
examination.
- Participants will sign an informed consent form
- Undergo 68Ga-FAPI PET/CT (PET/MR) before surgery or biopsy
- Surgical resection or puncture biopsy to obtain pathologic results. Diagnosis of
patients with malignant tumors at first diagnosis; clinical staging of tumors; and
clinical outcomes of patients with confirmed diagnoses will be assessed after
postoperative investigator follow-up.
The researchers will compare the FDG exams the participants have had to determine the
effectiveness of the fibroblast activating protein test.
Detailed description:
1. Title of research program Fibroblast activation protein(AFP) Positron Emission
Tomography(PET)-CT or -MR production in the diagnosis of malignant tumors, staging
and therapeutic evaluation of clinical applications.
Application.
2. Background Currently, 18F-FDG PET is one of the most commonly used methods for
diagnosis, staging, efficacy assessment, and prognosis evaluation of malignant
tumors. The basic principle of 18F-FDG PET is the Warburg effect. However, 18F-FDG
has its limitations, such as low specificity, low detection rate of small tumors,
mucin-secreting epithelial malignant tumors, squamous cell carcinomas, highly
differentiated neuroendocrine tumors, squamous cell carcinomas, highly
differentiated neuroendocrine tumors, and highly differentiated endocrine gland
malignancies, among others, have low uptake.
18F-FDG is a non-specific metabolic PET tracer that can reflect glucose metabolism in
malignant tumors. However, 18F-FDG can also be taken up by inflammatory lesions,
infectious lesions, benign tumors, etc. Therefore, 18F-FDG tumor imaging has relative
limitations. Nowadays, molecular imaging is changing from non-specific to specific
radiotracer imaging. Therefore, tumor-associated fibroblasts (CAFs) have gradually become
a new research hotspot.
Fibroblasts are the main host cells in the tumor microenvironment and are also the main
stromal cells of solid tumors, they can interact with tumor cells, make their own
morphology and physiological function changes, express a variety of cytokines, proteases,
adhesion, molecular, different degree increase of tumor cell malignant characterization,
and the occurrence of tumor, growth, blood vessel formation, invasion is closely related
to metastasis. It has been confirmed that FAP is expressed in melanoma, colorectal
cancer, breast cancer, pancreatic cancer, gastric cancer, lung cancer, esophageal cancer,
ovarian cancer, cervical cancer, endometrial cancer, oral squamous cell carcinoma, and
osteosarcoma, etc., and is associated with tumor growth and invasion. FAPαis a type II
transmembrane glycoprotein, consisting of a primary chain of 760 amino acids with a small
intracellular component or short cytoplasmic tail (6 amino acids), a transmembrane
component (19 amino acids) and a large extracellular component. The monomeric form of
FAPα is inactive but is activated by polymerization activity through
polymerization-activation to form either the homodimer FAPα/FAPα or the heterodimer
FAPα/FAPβ. This membrane-bound protein is one of the key components of the extracellular
matrix and plays an important role in regulating or remodeling the tumor
microenvironment. Fibroblast activation protein inhibitor Preparation (FAPI) is a novel
class of probes, and the enzymatic activity of FAP provides a new diagnostic and
therapeutic target. Therefore, the selection of FAPI to target FAP overexpression induced
by tumor-associated fibroblasts has become a new research hotspot. Currently, new
molecules such as FAPI-02, FAPI-04, FAPI-46, and other inhibitory ligands have been
designed, synthesized, and conducted in vitro and in vivo experiments. Because the
biological half-life of these probes matches the physical half-life of gallium-68
(Ga-68), if these molecules form new molecules after being labeled with Ga-68, the new
molecules become very promising molecular probes for research. PET/CT has been gradually
applied to the examination of malignant tumors, and can be used for the diagnosis of
tumors, clinical staging, and evaluation of therapeutic efficacy. PET/MRI is an emerging
molecular imaging method in recent years. With the popularization of integrated PET/MR
imaging, combining the higher resolution and morphology of MR imaging with the N-staging
and M-staging of PET has greatly improved the detection rate of some tumors and the
degree of tissue invasion around the lesion. In this study, investigators propose to use
fibroblast activation protein PET/CT and PET/MR for the diagnosis, staging, and
evaluation of treatment effects of malignant tumors, to evaluate its real value and to
make up for the insufficiency of 18F-FDG PET/CT.
3. Research objectives To study the value of FAPI PET/CT and PET/MR in diagnosing,
staging, and evaluating treatment effects of malignant tumors.
4. Types of study design, method of randomization, and level of blinding Type of study
design: observational study (prospective study).
5. Criteria for selection of participants
- 18 years ≤ 75 years of age;
- Patients with clinical suspicion of malignancy;
- No invasive tests or treatments recently;
- Blood routine: leukocyte > 4×10 9/L, neutrophil > 2×10 9/L, hemoglobin > 90g/L,
platelets > 100×10 9/L;
- Cardiac function: left ventricular ejection fraction >50%;
- Pulmonary function tests: FEV1 ≥1.2L, FEV1% ≥50% and DLCO ≥50%;
- Liver function: total bilirubin <1.5 times upper limit of normal (ULN); AST and ALT
<1.5 times ULN;
- Renal function: serum creatinine ≤ 1.5 times ULN, or glomerular filtration rate > 60
ml/min;
- Participants agreed to participate in this clinical trial and signed an informed
consent form;
- Good compliance and commitment to follow the study procedures and to cooperate in
the implementation of the full study;
- No birth plans for six months.
6. Exclusion criteria for participants
- Those with severe psychiatric symptoms, or those who are too confused to cooperate
with the examination;
- Pregnant and potentially pregnant women, lactating women;
- Those with poor compliance.
7. Calculate based on statistical principles, the number of cases required to
achieve the desired purpose of the study This was an exploratory observational
study and the sample size was not calculated based on statistical assumptions,
and the sample size was initially determined to be 60 cases.
8. Technology road map
9. Criteria for discontinuing clinical studies, provisions for ending clinical
studies
1. Significant errors in the clinical research protocol or serious deviations in
the implementation of the protocol that make it difficult to assess the utility
of the study;
2. The drug regulatory authority, government department or ethics committee asked
to suspend or end the study;
3. Circumstances in which other researchers do not consider it appropriate to
continue the study or find it difficult to do so.
10. Participant screening number, participant number, and case report form are
maintained participant Screening Number: a 1-sequential number, e.g., 1-1 for
the first participant; participant Number: a sequential number, e.g., 001 for
the first participant; Case report form retention: information is entered into
the CRF form by the project leader or other authorized investigator, and only
medically qualified investigators are allowed to complete the original clinical
assessment/safety data. Any changes made to the CRF form by the project leader
or other authorized researchers after the original data has been entered need
to be documented. Any modification of data that has been endorsed will require
the name of the researcher or other authorized researcher who modified it, the
date of the modification, and the reason for the modification (if the change is
minor).
11. Documentation of adverse events and methods of reporting serious adverse
events, management measures, modalities, timing and fate of follow-up visits
11.1Adverse events Adverse Event (AE) is an unfavorable medical event that
occurs during a clinical trial. Clinical trial Any adverse event that occurs
during the implementation should be faithfully recorded and analyzed for
reasons. Both anticipated and unanticipated adverse events should be recorded
and reported truthfully. Adverse events should be included as outcome variables
in the statistical analysis of clinical trials.
11.2Serious adverse event A serious Adverse Event (SAE) is a clinical trial event that
results in death or serious deterioration of health, including fatal illness or injury,
permanent defects in body structure or function, hospitalization or prolonged
hospitalization, or the need for medical or surgical intervention to avoid permanent
defects in body structure or function. Events that result in fetal distress, fetal death,
or congenital anomalies or congenital defects.
11.3Reporting procedures 11.3.1Reporting time frames In the event of AE or SAE in this
clinical trial, the investigator shall immediately take appropriate therapeutic measures
for the participant, notify the principal investigator, and report in writing to the
appropriate authorities within 24 hours once SAE has been determined.
11.3.2Reporting Sector The office of the clinical trial organization to which it belongs,
the sponsor, our Ethics Committee, as well as the drug supervision and management
department of the province, autonomous region, and municipality directly under the
central government where the clinical trial organization is located, and the competent
department of health and wellness.
11.3.3Reporting methods If an SAE occurs, the investigator completes the Adverse Event
Record Form and files the original Adverse Event Record Form in the investigator's file
folder.
11.3.4Processing and recording When an SAE or suspected SAE occurs, the investigator
immediately stops the trial and takes appropriate therapeutic measures, notifies the
principal investigator and the sponsor; the principal investigator makes a judgment about
the relevance of the SAE to the trial and records the occurrence, development, and
treatment of the SAE in as much detail as possible on the Adverse Event Record Form,
which is documented on the Case Report Form, signed and dated.
11.3.5follow-up If SAE is determined, the event must be followed until it appears to
improve, stabilizes, or, in the judgment of the principal investigator, does not require
follow-up.
12. Statistical analysis plan, definition, and selection of data sets for statistical
analysis 12.1General approach SPSS software was used for statistical analysis of
data. If the data were normally distributed, they were expressed as mean ± standard
deviation and compared using a two-sample t-test and one-way ANOVA. If the data were
not normally distributed, they were expressed as M(P5, P95) and compared using the
Mann-Whitneyu and Kruskal-WallisH rank sum tests. P<0.05 is considered a
statistically significant difference.
12.2Analysis of Primary and Secondary Study Endpoints Survival analysis was performed
using the Kaplan-Meier method to plot survival curves, and the log-rank test was used to
compare survival differences between groups.
13. Data management and confidentiality of information 13.1Data entry and modification
Data entry and modification will be done by the Department of Nuclear Medicine, and
data collection will be performed by clinical researchers under the supervision of
the person in charge, who will be responsible for the accuracy, completeness, and
timeliness of the reported data. All data should be clear to ensure accurate
interpretation and traceability. Clinical data will be maintained in a database,
which should be password-protected, and a logical proofreading process should be in
place when the database is created.
The Data Manager is responsible for reviewing and managing the entered data. In case of
doubt about the existence of data, the data manager will send the appropriate query to
the researcher, who will respond to the query sent by the data manager promptly, and the
data manager will be able to re-question the data if necessary.
13.2Confidentiality Program for Research Participant Information Participant's personal
information follows the principle of confidentiality. The investigator will replace the
participants' identifying information with a code name that does not contain
participants' name.
13.3Confidentiality Program for Research Data
14. Quality control and quality assurance in clinical research 14.1Conditions of
research units and training of personnel The department in which the research
project is located has the appropriate personnel, equipment, and first aid
facilities; All research participants (including doctors, nurses, and others) have
received appropriate training about the research and any information relevant to the
conduct of the research has been passed on to the relevant personnel; All equipment
has a technical inspection certificate from the technical supervision department
indicating that it is in good working order; During the trial study, the
investigators should be relatively fixed, and for the change of investigators in the
middle of the study, they should join the study after training, and the "Clinical
Trial Participant Contact Form" should be changed again.
14.2Modifications to the pilot program Any modifications to the trial protocol that would
affect the execution of the study, the purpose of the trial, the design of the trial, the
number of patient cases and the flow of the trial, etc., must be submitted as amendments
to the trial protocol, which must be agreed upon by the investigator and the Ethics
Committee before they can be implemented.
15. Study of related ethics Participants are not paid and do not incur any costs. The
study was conducted by China's Measures for Ethical Review of Biomedical Research
Involving Human Beings and international ethical guidelines such as the Declaration
of Helsinki.
16. Participant recruitment methods and the process of obtaining informed consent
Participant Recruitment Methods: Patients meeting the inclusion/exclusion criteria
were referred by the Department of Nuclear Medicine for inclusion in the clinical
study.
Informed Consent Process: Informed consent should be completed before the participant
agrees to participate in the study and should continue throughout the study. The informed
consent form was agreed upon by the Ethics Committee and should be read and signed by the
participants. The researcher will explain the research process answer questions from
participants and inform participants of the possible risks and their rights. Participants
may discuss with a family member or guardian before agreeing to participate. The
investigator must inform participants that participation in the study is voluntary and
that they may withdraw from the study at any time during the study. A copy of the
informed consent form can be provided to the study participant to keep. The rights and
welfare of subjects will be protected and it is emphasized that the quality of their
medical care will not be compromised by refusal to participate in research.
17. Expected progress and completion date of the clinical study 2022.4.28-2027.3.31
Screening of eligible participants, who underwent relevant examinations as arranged
by the investigator; 2027.4.1-2027.9.30 Complete the statistical analysis of the
experimental data.
18. Follow-up and medical measures at the end of the study Patients are followed up on a
long-term basis and assistance is provided accordingly.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 18 years ≤ 75 years of age;
- Patients with clinical suspicion of malignancy;
- No invasive tests or treatments recently;
- Blood routine: leukocyte > 4×109/L, neutrophil > 2×10 9/L, hemoglobin > 90g/L,
platelets > 100×10 9/L;
- Cardiac function: left ventricular ejection fraction >50%;
- Pulmonary function tests: FEV1 ≥1.2L, FEV1% ≥50% and DLCO ≥50%;
- Liver function: total bilirubin <1.5 times upper limit of normal (ULN); AST and ALT
<1.5 times ULN;
- Renal function: serum creatinine ≤ 1.5 times ULN, or glomerular filtration rate > 60
ml/min;
- Participants agreed to participate in this clinical trial and signed an informed
consent form;
- Good compliance and commitment to follow the study procedures and to cooperate in
the implementation of the full study;
- No birth plans for six months.
Exclusion Criteria:
- Those with severe psychiatric symptoms, or those who are too confused to cooperate
with the examination;
- Pregnant and potentially pregnant women, lactating women;
- Those with poor compliance.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
FirstHAnhuiMU
Address:
City:
Hefei
Zip:
230032
Country:
China
Start date:
April 28, 2022
Completion date:
March 31, 2027
Lead sponsor:
Agency:
The First Affiliated Hospital of Anhui Medical University
Agency class:
Other
Collaborator:
Agency:
National Natural Science Foundation of China
Agency class:
Other
Source:
The First Affiliated Hospital of Anhui Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06270394
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