A Phase 2/3,PSMA-T4, Prostate Cancer

Study Overview
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Brief Summary
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The objectives of this study are to evaluate the feasibility and safety of [99mTc]Tc-PSMA-T4 in the diagnosis and treatment planning of prostate cancer.

Detailed Description
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This is a Phase 2/3, open-label study, with multicohort design that will enroll up to approximately 80 subjects with prostate cancer (40 for cohort A, 20 for cohorts B and C). Cohort A - lymph node assessment in intermediate risk group The patients will undergo [99mTc]Tc-PSMA-T4 semiWB- SPECT/CT as an additional modality to contrast-enhanced (CE) multiparametric MRI (according to PI-RADS 2.1 protocol) with additional chest and abdominal CE computed tomography and [99mTc]Tc-MDP bone scan in unfavorable risk prostate cancer patients. Cohort B - general assessment (bone and lymph nodes) in high and very high-risk group The patients will undergo [99mTc]TcPSMA-T4 semi-WB- SPECT/CT and CE multiparametric MRI (according to PI-RADS 2.1 protocol), and chest and abdomen CE computed tomography, and skeletal scintigraphy ([99mTc]Tc-MDP bone scan). Cohort C - recurrent disease after definitive treatment (radiotherapy or surgery) The patients will undergo [99mTc]TcPSMA-T4 semiWB- SPECT/CT and the second confirmatory imaging modality or biopsy in the case of evidence on progressive disease (PSA persistence/recurrence or radiographic evidence of metastatic disease or clinical symptoms suggesting metastatic disease).

Official Title
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A Phase 2/3, Open-Label Study, to Evaluate the Feasibility and Safety of Intravenous [99mTc]Tc-PSMA-T4 in Subjects With Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: [99mTc]Tc-PSMA-T4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older. PS ECOG < 2 Prior diagnosis of any type of prostate cancer with a Gleason score (GlS) above 6. Confirmatory prostate biopsy, pelvic MRI and bone scan within 1 month before screening Willingness to participate in this study and to obtain written informed consent. Additional inclusion criteria for each cohort: Cohort A: Intermediate risk disease as defined by the most up-to-date version of National Comprehensive Cancer Network Guidelines for Prostate Cancer Greater than 10% chance of lymph node involvement assessed using the Memorial Sloan Kettering nomogram for probability of lymph node involvement in prostate cancer patients. Cohort B: High or very high-risk disease as defined by the most up-to-date version of National Comprehensive Cancer Network Guidelines for Prostate Cancer Cohort C: Biochemical failure after radical prostatectomy defined as failure of PSA to fall to undetectable levels (PSA persistence) or undetectable PSA after RP with a subsequent detectable PSA that increases on 2 or more determinations (PSA recurrence) OR biochemical failure after definitive radiotherapy based on Phoenix Consensus OR radiographic evidence of metastatic disease without PSA persistence/recurrence OR clinical symptoms suggesting distant metastases. Exclusion Criteria: No histopathological confirmation of prostate cancer. Patients with pacemakers or metal parts that prevent pelvic MRI to confirm the presence of prostate cancer. Infection with hepatitis B virus (including carriers) during screening, i.e. hepatitis B positive surface antigen (HBsAg) or positive hepatitis C (anti-HCV) antibody. Infected with acquired immunodeficiency (HIV). Abnormal liver function including a significant increase of liver enzymes like: ALAT, ASPAT, alkaline phosphatase (AP) greater than 5x upper limit normal (ULN) and an increase in bilirubin greater than 2xULN. Renal impairment including GFR <30 ml / min. Within 6 months before inclusion into the study: myocardial infarction or other cardiac events requiring hospitalization (unstable angina, etc.); Acute congestive heart failure or severe arrhythmia (like ventricular arrhythmia), second or higher degree atrio-ventricular (AV) heart block. Cerebrovascular accident, transient ischemic attack, acute stroke etc. Subjects with pulmonary embolism or deep vein thrombosis have been reported within the last 6 months. An active infection that the investigator considers precluding the patient from being included in the study, such as urinary tract infections, respiratory tract infections, and diabetes infection within the diabetic foot with osteomyelitis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The expected duration of participation for each subject is approximately 17 weeks. This includes up to 1 week for screening, 4 weeks for diagnostic procedures, and 12 weeks for safety evaluation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort A - lymph node assessment in intermediate risk group<br>The patients will undergo [99mTc]Tc-PSMA-T4 semiWB- SPECT/CT as an additional modality to contrast-enhanced (CE) multiparametric MRI (according to PI-RADS 2.1 protocol) with additional chest and abdominal CE computed tomography and [99mTc]Tc-MDP bone scan in unfavorable risk prostate cancer patients | Radiation: [99mTc]Tc-PSMA-T4<br>* [99mTc]Tc-PSMA-T4 for intravenous administration. The investigational medicinal product is to be prepared directly in a clinic by radiolabeling the radiopharmaceutical kit containing PSMA-T4 as a drug substance with sodium pertechnetate (99mTc) injection. The [99mTc]Tc-PSMA-T4 radiopharmaceutical should be used for targeted radionuclide SPECT imaging in patients with tumors and metastases of prostate cancer. The investigational medicinal product [99mTc]Tc-PSMA-T4 is dedicated for intravenous administration in radioactivity dose (555 - 740 MBq in cohorts A, B, C.<br>|
| Active Comparator: Cohort B - general assessment (bone and lymph nodes) in high and very high-risk group<br>The patients will undergo [99mTc]TcPSMA-T4 semi-WB- SPECT/CT and CE multiparametric MRI (according to PI-RADS 2.1 protocol), and chest and abdomen CE computed tomography, and skeletal scintigraphy ([99mTc]Tc-MDP bone scan). | Radiation: [99mTc]Tc-PSMA-T4<br>* [99mTc]Tc-PSMA-T4 for intravenous administration. The investigational medicinal product is to be prepared directly in a clinic by radiolabeling the radiopharmaceutical kit containing PSMA-T4 as a drug substance with sodium pertechnetate (99mTc) injection. The [99mTc]Tc-PSMA-T4 radiopharmaceutical should be used for targeted radionuclide SPECT imaging in patients with tumors and metastases of prostate cancer. The investigational medicinal product [99mTc]Tc-PSMA-T4 is dedicated for intravenous administration in radioactivity dose (555 - 740 MBq in cohorts A, B, C.<br>|
| Active Comparator: Cohort C - recurrent disease after definitive treatment (radiotherapy or surgery)<br>The patients will undergo [99mTc]TcPSMA-T4 semiWB- SPECT/CT and the second confirmatory imaging modality or biopsy in the case of evidence on progressive disease (PSA persistence/recurrence or radiographic evidence of metastatic disease or clinical symptoms suggesting metastatic disease). | Radiation: [99mTc]Tc-PSMA-T4<br>* [99mTc]Tc-PSMA-T4 for intravenous administration. The investigational medicinal product is to be prepared directly in a clinic by radiolabeling the radiopharmaceutical kit containing PSMA-T4 as a drug substance with sodium pertechnetate (99mTc) injection. The [99mTc]Tc-PSMA-T4 radiopharmaceutical should be used for targeted radionuclide SPECT imaging in patients with tumors and metastases of prostate cancer. The investigational medicinal product [99mTc]Tc-PSMA-T4 is dedicated for intravenous administration in radioactivity dose (555 - 740 MBq in cohorts A, B, C.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Endpoints | Clinical feasibility in each cohort: the diagnostic method will be deemed a feasible approach if at least 80% of participants in each cohort fulfil the criteria of sensitivity (true positive) and specificity (true negative) of PSMA-T4 WB-SPECT/CT - detection all lesions that are pathologically or radiologically confirmed or suspicious in other modalities recommended in a particular clinical situation by international guidelines for prostate cancer diagnosis and treatment (golden standards separate for each cohort). Feasibility = (number of patients with true positive and/or true negative without false positive and/or false negative results of PSMA-T4 WB-SPECT/CT x 100%) / all patients. The patients will undergo PSMA-T4 semiWB-SPECT/CT as an additional modality to contrast-enhanced (CE) multiparametric MRI (according to PI-RADS 2.1 protocol) withadditional chest and abdominal CE computed tomography and[ 99m Tc]Tc-MDP bone scan in unfavorable risk prostate cancer patients. | 17 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Outcome Measures | Sensitivity(number of true positives x 100%)/(number of true positives + number of false negatives) Specificity:(number of true negatives x 100%)/(number of true negatives + number of false positives) Positive and negative predictive value: Positive predictive value defined as number of true positives x 100%/number of true positives + number of false positives. Negative predictive value defined as number of true negatives x 100%/number of true negatives + number of false negatives. The patients will undergo PSMA-T4 semiWB-SPECT/CT as an additional modality to contrast-enhanced (CE) multiparametric MRI (according to PI-RADS 2.1 protocol) withadditional chest and abdominal CE computed tomography and[ 99m Tc]Tc-MDP bone scan in unfavorable risk prostate cancer patients. | 17 weeks |