Ignite Creation Date:
2024-05-06 @ 6:19 PM
Last Modification Date:
2024-10-26 @ 2:45 PM
Study NCT ID:
NCT05622162
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-05-22
First Post:
2022-11-09
Brief Title:
Prospective Comparative Study for Patients With Biochemical Recurrence Prostate Cancer Detecting by 18F-JK-PSMA-7
Sponsor:
ITEL Telecomunicazioni Srl
Organization:
ITEL Telecomunicazioni Srl
Study Overview
Official Title:
Phase III Multicentre Prospective Comparative Study of Detection Rate of 18F-JK-PSMA-7 and of 18F-fluorocholine in Patients With Biochemical Recurrence of Prostate Cancer After Previous Treatment With Curative Intent
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-05
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:
MIP7
Brief Summary:
The present study in patients with Prostate cancer and biochemical failure after surgery andor radical-postoperative Radio Therapy RT will evaluate if PETCT with 18F-JK-PSMA-7 compared to PET-CT 18F-Choline is able to identify the early pattern of biochemical recurrence andor metastatic sites so that the patient could be better managed with a benefit in survival
Detailed Description:
Investigational Product
The investigational product in this study is 18F-JK-PSMA-7 a fluorine-18 labelled ligand binding specifically to prostate specific membrane antigen PSMA
The investigational product 18F-JK-PSMA-7 is a diagnostic radiopharmaceutical for use with positron emission tomography PET
The active substance of the diagnostic radiopharmaceutical product is 18F-JK-PSMA-7
Fluorine F decays to stable oxygen O with a half-life of 110 minutes by emitting a positronic radiation of maximum energy of 634 keV followed by photonic annihilation radiations of 511 keV
The investigational product 18F-JK-PSMA-7 is a newly developed F-labelled PET tracer for functional imaging of PSMA expression
PSMA is a transmembrane glycoprotein that is expressed in a variety of cells and is characterized by its overexpression in Prostate Cancer The overexpression of PSMA has been observed both in primary Prostate Cancer as well as in metastatic lesions
The active substance of Comparator is 18F-Fluorocholine The Comparator will be a 18F-Fluorocholine with a Marketing Authorization in Italy that will be used in compliance with its Summary of Product Characteristics SmPC
18F-Fluorocholine is administrated as direct intravenous injection One single administration of 18F-Fluorocholine is scheduled in each patient included in this study
The analysis of images obtained with IMP 18F-JK-PSMA-7 and with Comparator 18F-fluorocholine will be performed by two independent off site experts blinded to any patients clinical data using the defined grid Discrepancies between results of the two observers will be recorded by the clinical manager and a consensus reading with third expert will be organized This reading will be used for determination of imaging performances
Study duration
The study starts with a screening visit -1 in which the medical history is collected then a PETTC examination T0 is performed The first examination will be performed with IMP
Whitin one month a second PET-TC is performed using the Comparator the other radiotracer T1 Only for IMP are requested additional test of the tolerability blood pressure heart rate and inspection of injection site The result of PET is analyzed by onsite reader then by two blind out-site readers blind to any clinical patients data A maximum wash-out period of 1 month is requested between the first and second reading performed by blind readers in order to avoid that the reading can be affected by the knowledge of the first PETTC examination
After 3 T2 and 6 T3 months from the last PETTC examination T1 a follow up visit will be performed in order to collect all the information related to procedures treatments andor examinations performed by the patient according to clinical practices
After last visit and last patient LVLP of each site the Assessment of Standard of Truth SOT is established by a panel of expert blinded to result of PETCT examination on the base of clinical data available in eCRF and Performance evaluation will be performed the Performance evaluation is an automatic determination the estimated time for these activities is 6 months
In conclusion each patient will be involved in the study about 7 months
Two PET-TC will perform within one month of distance according to the following order first the IMP than the Comparator
This sequence of administration is established in advance as the organizational model linked to the availability and management of the radiopharmaceutical not allow to perform a randomization
Risk and Benefits The potential benefit from performing 18F-JK-PSMA-7 PETCT in addition to PETCT with Comparator in patients with biochemical recurrence of Prostate Cancer after primary treatment with curative intent consists from expected earlier and more sensitive localization of sites of recurrent disease than with 18F-Fluorocholine PETCT which is currently the only one diagnostic radiopharmaceutical for use with PET approved for localization of lesions of recurrent Prostate Cancer The early recognition of the disease resumption can allow the use of targeted treatments that can postpone the use of hormone therapy or in case of metastatic disease the use of systemic treatment
In conclusion the benefit risk ratio for the patients involved is widely considered positive
Primary objective To show in an independent assessment by two readers blinded to clinical data the superiority of 18F-JK-PSMA-7 over 18F-Fluorocholine in patient-based detection rate of recurrent Prostate Cancer in patients with confirmed biochemical recurrence after treatment with curative intention
Based on available bibliographic data we hypothesize that the detection rate of 18F-JKPSMA-7 is at least 20 higher than that of 18F-Fluorocholine
Secondary objective
To evaluate the site-based sensitivity and specificity of 18F-JK-PSMA-7 and of 18F-Fluorocholine PETCT for recurrent Prostate Cancer
To evaluate the frequency of change of actual therapeutic management motivated by result of 18F-JK-PSMA-7 and by 18F-Fluorocholine PETCT in comparison with initially scheduled therapeutic management
To evaluate the discordance rate in 18F-JK-PSMA-7 and in 18F-Fluorocholine PETCT reading among two blinded readers
To evaluate the safety profile of 18F-JK-PSMA-7 and of 18F-Fluorocholine
Primary endpoints
The patient-based detection rate of 18F-JK-PSMA-7 and of 18F-Fluorocholine PETCT as a result of consensus of blind reading using an expert panel as a SOT The eventual major discordance of results of blind readings will be solved by third reader blinded to results of previous blind readings In particular the study hypohesizes a 20 diagnostic superiority of 18F-JK-PSMA-7 versus 18F- Fluorocholine The primary objective of the study is the identification of the possible best diagnostic rate of 18F-JK-PSMA-7 versus 18F- Fluorocholine in identiofying the reccurance of prostatic disesase in patients previusly subjected to prostectomy Furthemore the aim of the study is to evaluate the diagnostic accuracy of 18F-JK-PSMA-7 versus 18F- Fluorocholine even for low PSA levels where the 18F- Fluorocholine is considered to be insensitive in these conditions
Secondary endpoints
The site-based sensitivity and specificity of 18F-JK-PSMA-7 and of 18F-Fluorocholine PETCT of foci of recurrent Prostate Cancer
The change of actual therapeutic management motivated by result of 18F-JK-PSMA-7 and of 18F-Fluorocholine PETCT in comparison with initially scheduled therapeutic management
The discordance rate in 18F-JK-PSMA-7 and in 18F-Fluorocholine PETCT reading among two blinded readers
The adverse events or reactions related with use of 18F-JK-PSMA-7 and with use of 18F-fluorocholine
Statistical analysis The usual descriptive statistics sample size n mean standard deviation median and range will be provided for the quantitative variables as well as the actual and percentage for each category of the qualitative variables
Proportions comparisons Chi-square test X2 or Fisher test F when appropriated are the tests of choice If tests corrections are performed estimations for both the corrected and the non-corrected tests will be provided
To evaluate the study hypothesis the 95 confidence interval CI of the difference between the 18F-JK-PSMA-7 and 18F-Fluorocholine positive results will be evaluated as follows
1 the proportion of positives of the two tests will be said to be different if the CI of the difference does not include the number zero and consequently considered different at 5 statistical significance level
2 the extent in which the two tests differ will be reported using the width of the CI
3 the difference will be said to be clinically significant if the lower bound of the CI does not include the value 20 the superiority hypothesis
Sample Size The sample size was calculated on the basis of the diagnostic performances of the 18F-Fluorocholine PETCT present in the literature Three subgroups were identified
Groups are identified by PSA ngmL level A sample size calculation was performed for each subgroup considering the performance of the PET-18F-Fluorocholine and of the PET-18F-JK-PSMA-7 in that subgroup and computing the sample size adequate for testing the one-side hypothesis H0 pPSMA pPSMA - superiority margin versus H1 pPSMA pPSMA - superiority margin where pPSMA is supposed to be 08 in the first subgroup of PSA 095 in the second subgroup and 098 in the third one the superiority margin is equal to 02 in the first two subgroup of PSA and 015 in the third one
So with an α005 and a power 1-β 080
in the subgroup A 33 patients are needed in order to test H0 pPSMA06 08-02 vs H1 pPSMA06
in the subgroup B 21 patients are needed in order to test H0 pPSMA075 095-02 vs H1 pPSMA075
in the subgroup C 25 patients are needed in order to test H0 pPSMA083 098-015 vs H1 pPSMA083
The resulting sample size is 79 patients These resulting was incremented considering a dropout rate of 25 obtaining 79075 106 patients to be enrolled
The sponsor is responsible for implementing and maintaining quality assurance and quality control systems to ensure that trials are conducted and data are generated documented recorded and reported in compliance with the protocol GCP and the applicable regulatory requirements
The Sponsor is responsible for securing agreement from all involved parties to ensure direct access to all trial related sites source datadocuments and reports for the purpose of monitoring and auditing by the Sponsor and inspection by domestic and foreign regulatory authorities
Quality control should be applied to each stage of data handling to ensure that all data are reliable and have been processed correctly
Agreements made by the Sponsor with the investigatorinstitution and any other parties involved with the clinical trial should be in writing in protocol or in a separate agreement
This study will be performed in accordance with the principles stated in the Declaration of Helsinki and subsequent amendments and in accordance with the Good Clinical Practice Guideline CPMPICH13595
The investigational product in this study is 18F-JK-PSMA-7 a fluorine-18 labelled ligand binding specifically to prostate specific membrane antigen PSMA
The investigational product 18F-JK-PSMA-7 is a diagnostic radiopharmaceutical for use with positron emission tomography PET
The active substance of the diagnostic radiopharmaceutical product is 18F-JK-PSMA-7
Fluorine F decays to stable oxygen O with a half-life of 110 minutes by emitting a positronic radiation of maximum energy of 634 keV followed by photonic annihilation radiations of 511 keV
The investigational product 18F-JK-PSMA-7 is a newly developed F-labelled PET tracer for functional imaging of PSMA expression
PSMA is a transmembrane glycoprotein that is expressed in a variety of cells and is characterized by its overexpression in Prostate Cancer The overexpression of PSMA has been observed both in primary Prostate Cancer as well as in metastatic lesions
The active substance of Comparator is 18F-Fluorocholine The Comparator will be a 18F-Fluorocholine with a Marketing Authorization in Italy that will be used in compliance with its Summary of Product Characteristics SmPC
18F-Fluorocholine is administrated as direct intravenous injection One single administration of 18F-Fluorocholine is scheduled in each patient included in this study
The analysis of images obtained with IMP 18F-JK-PSMA-7 and with Comparator 18F-fluorocholine will be performed by two independent off site experts blinded to any patients clinical data using the defined grid Discrepancies between results of the two observers will be recorded by the clinical manager and a consensus reading with third expert will be organized This reading will be used for determination of imaging performances
Study duration
The study starts with a screening visit -1 in which the medical history is collected then a PETTC examination T0 is performed The first examination will be performed with IMP
Whitin one month a second PET-TC is performed using the Comparator the other radiotracer T1 Only for IMP are requested additional test of the tolerability blood pressure heart rate and inspection of injection site The result of PET is analyzed by onsite reader then by two blind out-site readers blind to any clinical patients data A maximum wash-out period of 1 month is requested between the first and second reading performed by blind readers in order to avoid that the reading can be affected by the knowledge of the first PETTC examination
After 3 T2 and 6 T3 months from the last PETTC examination T1 a follow up visit will be performed in order to collect all the information related to procedures treatments andor examinations performed by the patient according to clinical practices
After last visit and last patient LVLP of each site the Assessment of Standard of Truth SOT is established by a panel of expert blinded to result of PETCT examination on the base of clinical data available in eCRF and Performance evaluation will be performed the Performance evaluation is an automatic determination the estimated time for these activities is 6 months
In conclusion each patient will be involved in the study about 7 months
Two PET-TC will perform within one month of distance according to the following order first the IMP than the Comparator
This sequence of administration is established in advance as the organizational model linked to the availability and management of the radiopharmaceutical not allow to perform a randomization
Risk and Benefits The potential benefit from performing 18F-JK-PSMA-7 PETCT in addition to PETCT with Comparator in patients with biochemical recurrence of Prostate Cancer after primary treatment with curative intent consists from expected earlier and more sensitive localization of sites of recurrent disease than with 18F-Fluorocholine PETCT which is currently the only one diagnostic radiopharmaceutical for use with PET approved for localization of lesions of recurrent Prostate Cancer The early recognition of the disease resumption can allow the use of targeted treatments that can postpone the use of hormone therapy or in case of metastatic disease the use of systemic treatment
In conclusion the benefit risk ratio for the patients involved is widely considered positive
Primary objective To show in an independent assessment by two readers blinded to clinical data the superiority of 18F-JK-PSMA-7 over 18F-Fluorocholine in patient-based detection rate of recurrent Prostate Cancer in patients with confirmed biochemical recurrence after treatment with curative intention
Based on available bibliographic data we hypothesize that the detection rate of 18F-JKPSMA-7 is at least 20 higher than that of 18F-Fluorocholine
Secondary objective
To evaluate the site-based sensitivity and specificity of 18F-JK-PSMA-7 and of 18F-Fluorocholine PETCT for recurrent Prostate Cancer
To evaluate the frequency of change of actual therapeutic management motivated by result of 18F-JK-PSMA-7 and by 18F-Fluorocholine PETCT in comparison with initially scheduled therapeutic management
To evaluate the discordance rate in 18F-JK-PSMA-7 and in 18F-Fluorocholine PETCT reading among two blinded readers
To evaluate the safety profile of 18F-JK-PSMA-7 and of 18F-Fluorocholine
Primary endpoints
The patient-based detection rate of 18F-JK-PSMA-7 and of 18F-Fluorocholine PETCT as a result of consensus of blind reading using an expert panel as a SOT The eventual major discordance of results of blind readings will be solved by third reader blinded to results of previous blind readings In particular the study hypohesizes a 20 diagnostic superiority of 18F-JK-PSMA-7 versus 18F- Fluorocholine The primary objective of the study is the identification of the possible best diagnostic rate of 18F-JK-PSMA-7 versus 18F- Fluorocholine in identiofying the reccurance of prostatic disesase in patients previusly subjected to prostectomy Furthemore the aim of the study is to evaluate the diagnostic accuracy of 18F-JK-PSMA-7 versus 18F- Fluorocholine even for low PSA levels where the 18F- Fluorocholine is considered to be insensitive in these conditions
Secondary endpoints
The site-based sensitivity and specificity of 18F-JK-PSMA-7 and of 18F-Fluorocholine PETCT of foci of recurrent Prostate Cancer
The change of actual therapeutic management motivated by result of 18F-JK-PSMA-7 and of 18F-Fluorocholine PETCT in comparison with initially scheduled therapeutic management
The discordance rate in 18F-JK-PSMA-7 and in 18F-Fluorocholine PETCT reading among two blinded readers
The adverse events or reactions related with use of 18F-JK-PSMA-7 and with use of 18F-fluorocholine
Statistical analysis The usual descriptive statistics sample size n mean standard deviation median and range will be provided for the quantitative variables as well as the actual and percentage for each category of the qualitative variables
Proportions comparisons Chi-square test X2 or Fisher test F when appropriated are the tests of choice If tests corrections are performed estimations for both the corrected and the non-corrected tests will be provided
To evaluate the study hypothesis the 95 confidence interval CI of the difference between the 18F-JK-PSMA-7 and 18F-Fluorocholine positive results will be evaluated as follows
1 the proportion of positives of the two tests will be said to be different if the CI of the difference does not include the number zero and consequently considered different at 5 statistical significance level
2 the extent in which the two tests differ will be reported using the width of the CI
3 the difference will be said to be clinically significant if the lower bound of the CI does not include the value 20 the superiority hypothesis
Sample Size The sample size was calculated on the basis of the diagnostic performances of the 18F-Fluorocholine PETCT present in the literature Three subgroups were identified
Groups are identified by PSA ngmL level A sample size calculation was performed for each subgroup considering the performance of the PET-18F-Fluorocholine and of the PET-18F-JK-PSMA-7 in that subgroup and computing the sample size adequate for testing the one-side hypothesis H0 pPSMA pPSMA - superiority margin versus H1 pPSMA pPSMA - superiority margin where pPSMA is supposed to be 08 in the first subgroup of PSA 095 in the second subgroup and 098 in the third one the superiority margin is equal to 02 in the first two subgroup of PSA and 015 in the third one
So with an α005 and a power 1-β 080
in the subgroup A 33 patients are needed in order to test H0 pPSMA06 08-02 vs H1 pPSMA06
in the subgroup B 21 patients are needed in order to test H0 pPSMA075 095-02 vs H1 pPSMA075
in the subgroup C 25 patients are needed in order to test H0 pPSMA083 098-015 vs H1 pPSMA083
The resulting sample size is 79 patients These resulting was incremented considering a dropout rate of 25 obtaining 79075 106 patients to be enrolled
The sponsor is responsible for implementing and maintaining quality assurance and quality control systems to ensure that trials are conducted and data are generated documented recorded and reported in compliance with the protocol GCP and the applicable regulatory requirements
The Sponsor is responsible for securing agreement from all involved parties to ensure direct access to all trial related sites source datadocuments and reports for the purpose of monitoring and auditing by the Sponsor and inspection by domestic and foreign regulatory authorities
Quality control should be applied to each stage of data handling to ensure that all data are reliable and have been processed correctly
Agreements made by the Sponsor with the investigatorinstitution and any other parties involved with the clinical trial should be in writing in protocol or in a separate agreement
This study will be performed in accordance with the principles stated in the Declaration of Helsinki and subsequent amendments and in accordance with the Good Clinical Practice Guideline CPMPICH13595
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