Ignite Creation Date:
2024-05-06 @ 8:21 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06355427
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-04-09
First Post:
2024-03-15
Brief Title:
The Effect of 18F F-FAPI PET-CT on Management in Patients With Proximal Cholangiocarcinoma
Sponsor:
Mara Veenstra MD
Organization:
Erasmus Medical Center
Study Overview
Official Title:
The Effect of 18F F-FAPI PET-CT on Management in Patients With Potentially Resectable Biliary Tract Cancers Prospective Multicenter Study and Cost-effectivity Analysis
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FAPIChol
Brief Summary:
Background
Bile duct cancer cholangiocarcinoma represents the second most common type of hepatobiliary cancer worldwide with an incidence of 035 to 2 per 100000 annually Currently surgical resection is the only curative option However patients are not eligible for surgery if the tumor cannot be resected or the cancer has spread For this group of patients palliative chemotherapy is the most suited treatment option To find out if a patient is suited for surgery CT and MRI are performed These imaging techniques however struggle to correctly identify small cancer spreads that are smaller than 1 cm Therefore cancer that has already spread can be found during surgery In these cases the tumor cannot be removed and the surgery therefore has not been of any benefit for the patient These surgeries could be avoided by implementing a diagnostic tool with significantly higher accuracy than those currently used Single center studies have shown that fibroblast activation protein inhibitor FAPI PET-CT is a very promising technique for determining metastases in tumors with prominent desmoplastic reactions like cholangiocarcinoma The investigators predict that implementation of preoperative FAPI PET-CT could prevent futile surgery for at least half of patients in whom intra-operative metastasized disease is found using the current work-up
Patient population
Patients 18 years with potentially curable proximal cholangiocarcinoma perihilar intrahepatic and gall bladder cholangiocarcinoma who are planned to undergo surgery based on imaging using CT thoraxabdomen and MRI of the upper abdomen Exclusion criteria are previous abdominal surgery or chemotherapy known pregnancy or lactation and indication for FDG PET-CT
Participation in this study
Participation would mean to undergo FAPI PET-CT prior to the scheduled surgery This will take up about half a day of the participants time Afterwards participants receive questionnaires about quality of life and use of healthcare services over a period of six months in order for the researchers to be able to calculate the cost-effectiveness of additional FAPI PET-CT
Risks and benefits of participation
Patients may benefit directly from 18FF-FAPI PET-CT by allowing for more targeted treatment possibly avoiding futile surgery and receiving chemotherapy or best clinical support instead minimizing treatment delay Avoiding futile surgery will also prevent patients from being exposed to the risks and discomfort associated with surgery hospital stay possibility of intraoperative or postoperative complications postoperative pain and recovery and mortality
Potential risks and burdens associated with this study are an extra hospital visit and a time burden of approximately half a day Risks associated with administering FAPI are rebleed and infection Both risks have a minimal probability of onset and can usually easily be treated As 18FF-FAPI is a sub-pharmacologically micro-dosed diagnostic tracer the risk of allergic reactions is expected to be minimal and no tissue damage is expected The burden associated with undergoing a PET-CT may be laying still for a certain time and possible experience of claustrophobia Possible metastases of the cancer will have to be confirmed when suspicious findings are seen on FAPI PET-CT This could mean that participants will have to undergo additional testing such as imaging CT or MRI or biopsy Undergoing FAPI PET-CT prior to surgery will result in a surgical delay when compared with the current clinical practice The investigators do not expect this delay to influence the patients prognosis Follow-up will result in a time burden for patients to answer questionnaires on a two-weekly or monthly basis
Bile duct cancer cholangiocarcinoma represents the second most common type of hepatobiliary cancer worldwide with an incidence of 035 to 2 per 100000 annually Currently surgical resection is the only curative option However patients are not eligible for surgery if the tumor cannot be resected or the cancer has spread For this group of patients palliative chemotherapy is the most suited treatment option To find out if a patient is suited for surgery CT and MRI are performed These imaging techniques however struggle to correctly identify small cancer spreads that are smaller than 1 cm Therefore cancer that has already spread can be found during surgery In these cases the tumor cannot be removed and the surgery therefore has not been of any benefit for the patient These surgeries could be avoided by implementing a diagnostic tool with significantly higher accuracy than those currently used Single center studies have shown that fibroblast activation protein inhibitor FAPI PET-CT is a very promising technique for determining metastases in tumors with prominent desmoplastic reactions like cholangiocarcinoma The investigators predict that implementation of preoperative FAPI PET-CT could prevent futile surgery for at least half of patients in whom intra-operative metastasized disease is found using the current work-up
Patient population
Patients 18 years with potentially curable proximal cholangiocarcinoma perihilar intrahepatic and gall bladder cholangiocarcinoma who are planned to undergo surgery based on imaging using CT thoraxabdomen and MRI of the upper abdomen Exclusion criteria are previous abdominal surgery or chemotherapy known pregnancy or lactation and indication for FDG PET-CT
Participation in this study
Participation would mean to undergo FAPI PET-CT prior to the scheduled surgery This will take up about half a day of the participants time Afterwards participants receive questionnaires about quality of life and use of healthcare services over a period of six months in order for the researchers to be able to calculate the cost-effectiveness of additional FAPI PET-CT
Risks and benefits of participation
Patients may benefit directly from 18FF-FAPI PET-CT by allowing for more targeted treatment possibly avoiding futile surgery and receiving chemotherapy or best clinical support instead minimizing treatment delay Avoiding futile surgery will also prevent patients from being exposed to the risks and discomfort associated with surgery hospital stay possibility of intraoperative or postoperative complications postoperative pain and recovery and mortality
Potential risks and burdens associated with this study are an extra hospital visit and a time burden of approximately half a day Risks associated with administering FAPI are rebleed and infection Both risks have a minimal probability of onset and can usually easily be treated As 18FF-FAPI is a sub-pharmacologically micro-dosed diagnostic tracer the risk of allergic reactions is expected to be minimal and no tissue damage is expected The burden associated with undergoing a PET-CT may be laying still for a certain time and possible experience of claustrophobia Possible metastases of the cancer will have to be confirmed when suspicious findings are seen on FAPI PET-CT This could mean that participants will have to undergo additional testing such as imaging CT or MRI or biopsy Undergoing FAPI PET-CT prior to surgery will result in a surgical delay when compared with the current clinical practice The investigators do not expect this delay to influence the patients prognosis Follow-up will result in a time burden for patients to answer questionnaires on a two-weekly or monthly basis
Detailed Description:
Rationale
Bile duct cancer cholangiocarcinoma represents the second most common type of hepatobiliary cancer worldwide with an incidence of 035 to 2 per 100000 annually Currently surgical resection is the only curative option However patients are not eligible for surgery if vascular invasion distant tumor positive lymph nodes peritoneal metastases or organ metastases are found on preoperative imaging For this group of patients palliative chemotherapy is the most suited treatment option The preoperative imaging currently includes CT MRI and FDG PET-CT In around 29 of potentially resectable tumors based on preoperative imaging metastases are found during subsequent surgery These explorations could be avoided by implementing a diagnostic tool with significantly higher accuracy than those currently used Single center studies have shown that fibroblast activation protein inhibitor FAPI PET-CT is a very promising technique for determining metastases in tumors with prominent desmoplastic reactions like cholangiocarcinoma Our systematic review has shown it is superior to the commonly used FDG PET-CT for this indication The investigators predict that implementation of preoperative FAPI PET-CT could alter treatment course for at least half 13 of patients in whom intra-operative metastasized disease is found using the current work-up
Objective
The primary aim of this study is to assess whether preoperative 18FF-FAPI PET-CT in addition to standard preoperative imaging can successfully identify metastasized disease and change treatment plan in patients with potentially resectable proximal bile duct cancer intrahepatic perihilar and gall bladder cholangiocarcinoma This study also aims to evaluate if adding 18FF-FAPI PET-CT to preoperative imaging is cost-effective
Main trial endpoints
The main endpoint is the diagnostic accuracy sensitivity specificity positive predictive value negative predictive value of 18FF-FAPI PET-CT
Secondary trial endpoints
Diagnostic accuracy of 18FF-FAPI PET-CT per abdominal region and per lesion
The number of additional significant findings on 18FF-FAPI PET-CT
Change of treatment true change and virtual change
The number of times readers conclusions differed and why
Cost-effectiveness analysis budget impact analysis BIA sector costs societal costs health-related quality of life HRQoL
The number of additional significant findings on 18FF-FAPI PET-CT
Number of days between date of first imaging CTMRI and starting date of chemotherapy palliative therapy or surgical resection
The incidence and severity of AEs and SAEs according to CTCAEv5
VOI TTP K1 and k2 SUV and TBR in a subgroup of patients
Trial design
Prospective multicenter observational cohort study expected total duration 4 years Participants will be participating for at least six months
Trial population
Patients 18 years with potentially curable proximal cholangiocarcinoma perihilar intrahepatic and gall bladder cholangiocarcinoma who are planned to undergo surgery based on imaging using CT thoraxabdomen and MRI of the upper abdomen Exclusion criteria are previous abdominal surgery or chemotherapy known pregnancy or lactation and indication for FDG PET-CT
Interventions
If patients are deemed eligible for surgery laparoscopy or laparotomy by the weekly organ-specific multidisciplinary team MDT including an abdominal nuclear medicine specialist radiologist surgeon gastroenterologisthepatologist oncologist and optionally pathologist patients will be asked to participate in the study After inclusion patients will receive additional 18FF-FAPI PET-CT Patients who underwent 18FF-FAPI PET-CT will undergo follow-up for at least six months if clinically advisable Follow-up includes information regarding additional imaging surgery or complications To determine cost-effectiveness patients medical consumption will be elicited using two questionnaires Patients will be asked to fill out the institute for Medical Technology Assessment iMTA Medical Consumption Questionnaire iMCQ at three and six months after their initial CTMRI imaging before 18FF-FAPI PET-CT or surgery Patients will also be asked to fill out the European Organisation for Research and Treatment of Cancer EORTC groups QLQ-C30 and QLQ-BIL21 questionnaires and the EuroQol EQ Groups EQ-5D-5L questionnaire once every two weeks during the first two months after 18FF-FAPI PET-CT and then once every four weeks until six months follow-up
Risks and benefits
Patients may benefit directly from 18FF-FAPI PET-CT by allowing for more targeted treatment possibly avoiding futile surgery and receiving chemotherapy or best clinical support instead minimizing treatment delay Avoiding futile surgery will also prevent patients from being exposed to the risks and discomfort associated with surgery hospital stay possibility of intraoperative or postoperative complications postoperative pain and recovery and mortality
Potential risks and burdens associated with this study are an extra site visit and a time burden of approximately half a day Risks associated with vena puncture are rebleed and infection Both risks have a minimal probability of onset and when anticipated upon are not expected to have significant clinical consequences Risks associated with the administration of the study agent are allergic reactions and radiation burden 18FF-FAPI is a sub-pharmacologically micro-dosed diagnostic tracer which is why the risk of allergic reactions is expected to be minimal and no tissue damage is expected The burden associated with undergoing a PET-CT may be laying still for a certain time and possible experience of claustrophobia Metastases will have to be confirmed when suspicious findings are seen on 18FF-FAPI PET-CT This could mean subjects will have to undergo additional testing such as imaging CT or MRI or biopsy If these additional tests are negative for metastases the subjects exploratory surgery will have been needlessly delayed Having to undergo 18FF-FAPI PET-CT prior to surgery will also result in a surgical delay when compared with the current clinical practice The investigators do not expect this delay to influence the subjects prognosis Follow-up will result in a time burden for patients to answer questionnaires on a two-weekly or monthly basis
Bile duct cancer cholangiocarcinoma represents the second most common type of hepatobiliary cancer worldwide with an incidence of 035 to 2 per 100000 annually Currently surgical resection is the only curative option However patients are not eligible for surgery if vascular invasion distant tumor positive lymph nodes peritoneal metastases or organ metastases are found on preoperative imaging For this group of patients palliative chemotherapy is the most suited treatment option The preoperative imaging currently includes CT MRI and FDG PET-CT In around 29 of potentially resectable tumors based on preoperative imaging metastases are found during subsequent surgery These explorations could be avoided by implementing a diagnostic tool with significantly higher accuracy than those currently used Single center studies have shown that fibroblast activation protein inhibitor FAPI PET-CT is a very promising technique for determining metastases in tumors with prominent desmoplastic reactions like cholangiocarcinoma Our systematic review has shown it is superior to the commonly used FDG PET-CT for this indication The investigators predict that implementation of preoperative FAPI PET-CT could alter treatment course for at least half 13 of patients in whom intra-operative metastasized disease is found using the current work-up
Objective
The primary aim of this study is to assess whether preoperative 18FF-FAPI PET-CT in addition to standard preoperative imaging can successfully identify metastasized disease and change treatment plan in patients with potentially resectable proximal bile duct cancer intrahepatic perihilar and gall bladder cholangiocarcinoma This study also aims to evaluate if adding 18FF-FAPI PET-CT to preoperative imaging is cost-effective
Main trial endpoints
The main endpoint is the diagnostic accuracy sensitivity specificity positive predictive value negative predictive value of 18FF-FAPI PET-CT
Secondary trial endpoints
Diagnostic accuracy of 18FF-FAPI PET-CT per abdominal region and per lesion
The number of additional significant findings on 18FF-FAPI PET-CT
Change of treatment true change and virtual change
The number of times readers conclusions differed and why
Cost-effectiveness analysis budget impact analysis BIA sector costs societal costs health-related quality of life HRQoL
The number of additional significant findings on 18FF-FAPI PET-CT
Number of days between date of first imaging CTMRI and starting date of chemotherapy palliative therapy or surgical resection
The incidence and severity of AEs and SAEs according to CTCAEv5
VOI TTP K1 and k2 SUV and TBR in a subgroup of patients
Trial design
Prospective multicenter observational cohort study expected total duration 4 years Participants will be participating for at least six months
Trial population
Patients 18 years with potentially curable proximal cholangiocarcinoma perihilar intrahepatic and gall bladder cholangiocarcinoma who are planned to undergo surgery based on imaging using CT thoraxabdomen and MRI of the upper abdomen Exclusion criteria are previous abdominal surgery or chemotherapy known pregnancy or lactation and indication for FDG PET-CT
Interventions
If patients are deemed eligible for surgery laparoscopy or laparotomy by the weekly organ-specific multidisciplinary team MDT including an abdominal nuclear medicine specialist radiologist surgeon gastroenterologisthepatologist oncologist and optionally pathologist patients will be asked to participate in the study After inclusion patients will receive additional 18FF-FAPI PET-CT Patients who underwent 18FF-FAPI PET-CT will undergo follow-up for at least six months if clinically advisable Follow-up includes information regarding additional imaging surgery or complications To determine cost-effectiveness patients medical consumption will be elicited using two questionnaires Patients will be asked to fill out the institute for Medical Technology Assessment iMTA Medical Consumption Questionnaire iMCQ at three and six months after their initial CTMRI imaging before 18FF-FAPI PET-CT or surgery Patients will also be asked to fill out the European Organisation for Research and Treatment of Cancer EORTC groups QLQ-C30 and QLQ-BIL21 questionnaires and the EuroQol EQ Groups EQ-5D-5L questionnaire once every two weeks during the first two months after 18FF-FAPI PET-CT and then once every four weeks until six months follow-up
Risks and benefits
Patients may benefit directly from 18FF-FAPI PET-CT by allowing for more targeted treatment possibly avoiding futile surgery and receiving chemotherapy or best clinical support instead minimizing treatment delay Avoiding futile surgery will also prevent patients from being exposed to the risks and discomfort associated with surgery hospital stay possibility of intraoperative or postoperative complications postoperative pain and recovery and mortality
Potential risks and burdens associated with this study are an extra site visit and a time burden of approximately half a day Risks associated with vena puncture are rebleed and infection Both risks have a minimal probability of onset and when anticipated upon are not expected to have significant clinical consequences Risks associated with the administration of the study agent are allergic reactions and radiation burden 18FF-FAPI is a sub-pharmacologically micro-dosed diagnostic tracer which is why the risk of allergic reactions is expected to be minimal and no tissue damage is expected The burden associated with undergoing a PET-CT may be laying still for a certain time and possible experience of claustrophobia Metastases will have to be confirmed when suspicious findings are seen on 18FF-FAPI PET-CT This could mean subjects will have to undergo additional testing such as imaging CT or MRI or biopsy If these additional tests are negative for metastases the subjects exploratory surgery will have been needlessly delayed Having to undergo 18FF-FAPI PET-CT prior to surgery will also result in a surgical delay when compared with the current clinical practice The investigators do not expect this delay to influence the subjects prognosis Follow-up will result in a time burden for patients to answer questionnaires on a two-weekly or monthly basis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None