Trial Title:
Prospective Comparative Study for Patients With Biochemical Recurrence Prostate Cancer Detecting by 18F-JK-PSMA-7
NCT ID:
NCT05622162
Condition:
Prostate Cancer
18F- Fluorocholine
PSMA PET
Radiotherapy
Prostatectomy
Tumor of Prostate
Conditions: Official terms:
Prostatic Neoplasms
Recurrence
Radiopharmaceuticals
18F-JK-PSMA-7
Conditions: Keywords:
Prostate Cancer
Prostatectomy
diagnostic radiopharmaceutical
PET
CT
PSA
Biochemical Recurrence
18F- Fluorocholine
18F-JK-PSMA-7
PSMA
Standard of truth
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Prospective, multicentric, comparative (controlled), phase III study of diagnostic
performance with blind reading and standard of truth.
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
The blind readers of PET/CT examinations with Investigational product (18F-JK-PSMA-7) and
with Comparator (18F-fluorocholine) will be blinded to any clinical data of patient.
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
patient´s clinical data, using the defined grid (Appendix I). 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.
Wash-out period of at least one month is ensured between reading of examinations with
Investigational product (18F-JK-PSMA-7) and with Comparator (18F-Fluorocholine) for each
blind reader.
Intervention:
Intervention type:
Drug
Intervention name:
Radiopharmaceutical 18F-JK-PSMA-7
Description:
The Investigational product 18F-JK-PSMA-7 is a diagnostic radiopharmaceutical for use
with positron emission tomography.
18F-JK-PSMA-7 is administered as direct intravenous injection. One single administration
of 2-4 MBq/kg of 18F-JK-PSMA-7 is scheduled in each patient included in this study.
Arm group label:
Interventional and Comparator
Other name:
18F-JK-PSMA-7
Intervention type:
Drug
Intervention name:
Radiopharmaceutical 18F-Fluorocholine
Description:
The active substance of Comparator is 18F-Fluorocholine. The Comparator will be a
18F-Fluorocholine with a Marketing Authorisation 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.
Arm group label:
Interventional and Comparator
Other name:
18F-Fluorocholine
Summary:
The present study in patients with Prostate cancer and biochemical failure after surgery
and/or radical-postoperative Radio Therapy (RT) will evaluate if PET/CT with
18F-JK-PSMA-7 compared to PET-CT 18F-Choline is able to identify the early pattern of
biochemical recurrence and/or 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
patient´s 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 PET/TC 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
patient's 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 PET/TC examination.
- After 3 (T2) and 6 (T3) months from the last PET/TC examination (T1) a follow up
visit will be performed in order to collect all the information related to
procedures (treatments and/or 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 PET/CT
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 PET/CT in addition
to PET/CT 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 PET/CT
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 PET/CT 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 PET/CT in comparison with initially
scheduled therapeutic management;
- To evaluate the discordance rate in 18F-JK-PSMA-7 and in 18F-Fluorocholine PET/CT
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 PET/CT 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
PET/CT of foci of recurrent Prostate Cancer;
- The change of actual therapeutic management motivated by result of 18F-JK-PSMA-7 and
of 18F-Fluorocholine PET/CT in comparison with initially scheduled therapeutic
management;
- The discordance rate in 18F-JK-PSMA-7 and in 18F-Fluorocholine PET/CT 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 PET/CT present in the literature. Three subgroups were identified.
Groups are identified by PSA ng/mL 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 0.8 in the first subgroup of PSA, 0.95
in the second subgroup and 0.98 in the third one; the superiority margin is equal to 0.2
in the first two subgroup of PSA and 0.15 in the third one.
So, with an α=0.05 and a power (1-β) = 0.80:
- in the subgroup A, 33 patients are needed in order to test H0: pPSMA=0.6 (0.8-0.2)
vs H1: pPSMA>0.6;
- in the subgroup B, 21 patients are needed in order to test H0: pPSMA=0.75 (0.95-0.2)
vs H1: pPSMA>0.75;
- in the subgroup C, 25 patients are needed in order to test H0: pPSMA=0.83
(0.98-0.15) vs H1: pPSMA>0.83.
The resulting sample size is 79 patients. These resulting was incremented considering a
dropout rate of 25%, obtaining 79/0.75 = 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 data/documents, 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 investigator/institution 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 (CPMP/ICH/135/95).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histological confirmation of prostate malignancy
2. Patient must have had their primary PCa treated with surgery and/or radiation
therapy; salvage radiation to the prostate bed or pelvis is allowed
3. Patient must be ≥ 18 years of age
4. Patient must have an Eastern Cooperative Oncology Group performance status ≤ 2
5. For patients treated with radical prostatectomy: arise of PSA ≥ 0.2 ng/mL (performed
in the last month) or a rise of 2 ng/mL or more above the nadir PSA after definitive
radiation therapy defined by two subsequent PSA assessments performed over a 3-month
period in the same laboratory
6. Absence of any of the exclusion criteria
7. Signed informed consent
Exclusion Criteria:
1. Absence of any of the inclusion criteria;
2. More than 3 years of androgen deprivation therapy (ADT), with less than 3 months
from the last treatment
3. Spinal cord compression or impending spinal cord compression
4. Receipt of any other investigational agents in the previous 3 months
5. Inability to lie flat during or tolerate PET/CT
6. Hypersensitivity to active substance or any of excipients of Investigational
Medicinal Product or Comparator
7. Life expectancy <6 months
8. ECOG performance status >2
9. Refusal to sign informed consent
10. Participation in a concurrent clinical trial
11. Concomitant active malignancy
12. Subject deprived of its freedom by administrative or legal decision or who is under
guardianship
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
I.R.S.T. Srl Irccs
Address:
City:
Meldola
Country:
Italy
Facility:
Name:
Ospedale Classificato Sacro Cuore - Don Calabria
Address:
City:
Negrar
Country:
Italy
Start date:
December 19, 2022
Completion date:
June 2024
Lead sponsor:
Agency:
ITEL Telecomunicazioni Srl
Agency class:
Industry
Collaborator:
Agency:
Advice Pharma Group srl
Agency class:
Industry
Source:
ITEL Telecomunicazioni Srl
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05622162
https://www.certifico.com/chemicals/legislazione-chemicals/10448-decreto-9-febbraio-2020-10-edizione-della-farmacopea-europea
