[18F]Florastamin PET/CT Imaging Examination in Patients With Suspected Recurrent or Metastatic Prostate Cancer

[18F]Florastamin PET/CT Imaging Examination in Patients With Suspected Recurrent or Metastatic Prostate Cancer

A Multi-center, Open-label, Single Arm Phase III Clinical Trial for the Diagnostic Efficacy Assessment and Safety Evaluation by [18F]Florastamin PET/CT Imaging Examination in Patients With Suspected Recurrent or Metastatic Prostate Cancer

This is a multi-center, open-label, single arm Phase III clinical trial for the diagnostic efficacy assessment and safety evaluation by [18F]Florastamin PET/CT imaging examination to determine the presence of recurrent or metastatic prostate cancer in patients whose recurrent or metastatic lesions have been confirmed through the conventional imaging.

In this study, the diagnostic efficacy of [18F]Florastamin PET/CT imaging at detecting recurrent or metastatic prostate cancer will be evaluated according to the histopathology truth standard in prostate cancer patients whose recurrent or metastatic lesions have been confirmed with the conventional imaging. Patients who meet the inclusion/exclusion criteria of the clinical study protocol will be enrolled, who then will undergo a biopsy or pelvic lymph node dissection (PLND) for one or more lesion locations confirmed with the conventional imaging within 28 days from [18F]Florastamin PET/CT scanning. After the biopsy or PLND, follow-up will be carried out for 2 weeks. However, if necessary, based on the judgment of the principal investigator, additional visits may be made. Baseline Procedures At the baseline visit, the conventional imaging will be performed. The results of whole-body bone scan and gadolinium-enhanced MRI (for the chest, abdomen or pelvis) within 6 weeks prior to [18F]Florastamin PET/CT scanning will be collected. All conventional imaging examinations will be evaluated by the study site. At the time of whole-body bone scanning, examinations will be performed 2 hours after the contrast agent 99mTc-HDP 20 to 30 mCi is administered intravenously. At the time of gadolinium-enhanced MRI scanning (for the chest, abdomen or pelvis), the gadolinium contrast agent (Gadobrix 1 cc/kg) will be administered intravenously. Biopsy and PLND Images collected through the conventional imaging during the baseline visit can be selectively used for images to guide a biopsy, and images to decide on biopsy sites will be read by the study site. If more than one legions are identified through the image reading, an intermediary radiology specialist will choose a lesion for which to perform a biopsy; however, among the lesions identified, the one determined to be safe for the subject in the investigator's judgment will be preferred as a site on which to perform a biopsy or PLND, and the final biopsy site will be decided after checking its justification through consultation with the intermediary Department of Radiology. A biopsy can be performed while hospitalized, if necessary. Pelvic lymph node dissection (PLND) is surgery to remove the lymph nodes from the pelvis, which is part of a radical prostatectomy, so it is typically performed with hospitalization. Florastamin PET imaging (PSMA-PET Imaging) Uptake values of [18F]Florastamin in the region of interest (ROI) of Florastamin PET imaging are evaluated by an independent evaluator. The independent evaluator records all uptake values observed in the lesion, and analyzes uptake values in the lesion where the biopsy has been performed during analysis of efficacy evaluation. Biopsy and Histopathology Tissues removed through a biopsy or PLND are delivered to the Department of Pathology in accordance with the guidelines of the study site and slides by biopsy or PLND site are produced. A pathologist at the study site performs histopathological evaluation of the slides produced with blinded to results of [18F]Florastamin PET/CT examinations. An area on which a biopsy or PLND has been performed and histopathological results thereof are collected in the eCRF. Histopathology truth standard Tissues removed with a standard method in more than one lesion locations confirmed by the conventional imaging performed prior to [18F]Florastamin PET/CT scanning are evaluated in terms of whether there is prostate cancer, there are any other tumors, it is impossible to read, etc. In addition, the positive/negative result of [18F]Florastamin PET/CT imaging in the applicable location is evaluated by an independent evaluator.

The positive predictive values (PPV) of [18F]Florastamin PET/CT imaging for the detection of recurrent or metastatic prostate cancer in subjects are evaluated.

A single dose of [F-18]Florastamin at 10 ± 1 mCi is intravenously administered only to the subjects who meet the inclusion/exclusion criteria, and then [F-18]Florastamin PET/CT imaging is performed from the head to thigh after 105 ± 15 minutes (care should be taken to prevent extravasation of the radiopharmaceutical product).

The positive predictive values (PPV) of [18F]Florastamin PET/CT imaging for the detection of recurrent or metastatic prostate cancer in subjects are evaluated. The PPV is calculated by TP/(TP+FP) x 100% for patients with positive [ 18F]Florastamin PET/CT. True positive is defined as being determined to be positive for prostate cancer according to histopathological results of tissues removed from [18F]Florastamin PET/CT and a biopsy or PLND. False positive is defined as being determined negative for prostate cancer according to the histopathological results of tissues removed through a biopsy or PLND, but determined positive for prostate cancer by [18F]Florastamin PET/CT.

[18F]Florastamin PET/CT conducts at V2(1 Day/Efficacy & Safety evaluation). Biopy or PLND conducts V3(1Day ~ 28Day/Efficacy & Safety evaluation).

Detection rates of [18F]Florastamin PET/CT imaging in the lesion location (prostate, bones, lymph nodes (inside and outside the pelvis), soft tissues, etc.) are evaluated. Detection rates of [18F]Florastamin PET/CT imaging are defined as the percentage of subjects who have tested positive according to the [18F]Florastamin PET/CT imaging results in any random lesion location such as prostate, bones, lymph nodes (inside and outside the pelvis), and soft tissues.

[18F]Florastamin PET/CT conducts at V2(1 Day/Efficacy & Safety evaluation). Biopy or PLND conducts V3(1Day ~ 28Day/Efficacy & Safety evaluation).

The sensitivity of [18F]Florastamin PET/CT imaging for the detection of recurrent or metastatic prostate cancer in subjects is evaluated. The sensitivity is calculated by TP/(TP+FN) x 100% for patients with positive [18F]Florastamin PET/CT. True positive is defined as being determined to be positive for prostate cancer according to [ 18F]Florastamin PET/CT and histopathological results. False positive is defined as being determined negative for prostate cancer according to the histopathological results but determined positive for prostate cancer by [18F]Florastamin PET/CT.

[18F]Florastamin PET/CT conducts at V2(1 Day/Efficacy & Safety evaluation). Biopy or PLND conducts V3(1Day ~ 28Day/Efficacy & Safety evaluation).

The positive predictive values (PPV) Comparison of [18F]Florastamin PET/CT imaging and conventional imaging

The positive predictive values (PPV) of [18F]Florastamin PET/CT imaging and of the conventional imaging (whole-body bone scan, CT, MRI or ultrasound) are compared and evaluated to detect recurrent or metastatic prostate cancer in subjects.

[18F]Florastamin PET/CT conducts at V2(1 Day/Efficacy & Safety evaluation). Biopy or PLND conducts V3(1Day ~ 28Day/Efficacy & Safety evaluation).

Standard uptake values (SUVpeak, SUVmax, and SUVr) of [18F]Florastamin for each lesion location (prostate, bones, lymph nodes (inside and outside the pelvis), soft tissues, etc.) decided on by the independent evaluator according to the histopathological results (positive and negative for prostate cancer) are evaluated.

[18F]Florastamin PET/CT conducts at V2(1 Day/Efficacy & Safety evaluation). Biopy or PLND conducts V3(1Day ~ 28Day/Efficacy & Safety evaluation).

The percentage of subjects who have a different lesion location found by [18F]Florastamin PET/CT that was not identified through the conventional imaging but a biopsy conducted there has confirmed the lesion is evaluated.

Conventional imaging conduct at V1(-42 Days ~ 1 Days). [18F]Florastamin PET/CT conducts at V2(1 Day/Efficacy & Safety evaluation). Biopy or PLND conducts V3(1Day ~ 28Day/Efficacy & Safety evaluation).

Inclusion Criteria: Male aged 19 and older Patients histopathologically diagnosed with prostate cancer Patients who can undergo a percutaneous biopsy or PLND for more than one lesion locations with locally recurrent, new or advanced metastasis as confirmed by MRI or whole-body bone scan performed within 6 weeks prior to screening Patients whose survival is expected to be at least 6 months with ECOG Performance Status ≤ 2 Those whose ICF was signed by themselves or their legal guardian or representative after sufficient explanation was given by the investigator about the study objectives, details, characteristics of the investigational device, etc. before enrolled for the study. Exclusion Criteria: Subjects who have the following disease within 6 months prior to screening: Heart failure that falls into Class III or IV heart failure classified by New York Heart Association; Embolism pulmonary, acute coronary syndrome (unstable angina or myocardial infarction); Acute severe respiratory syndrome; Cerebrovascular disease such as stroke; Uncontrollable hypertension (SBP > 160 mmHg or DBP > 90 mmHg); Uncontrollable heart arrhythmia; Blood clotting disorder. Patients who are receiving radiation therapy or ablative therapy on the prostate bed within 12 weeks prior to screening Patients whose method of systemic treatment for prostate cancer (e.g., hormone therapy, biological therapy, radiation therapy, or chemotherapy) has changed within 3 months prior to screening, or who have to change orstart systemic treatment for prostate cancer while the study is being conducted (until before a biopsy or PLND) However, when systemic treatment has changed into watchful waiting, the patient can participate in the study. According to the laboratory test results, patients who meet the following criteria: Platelet counts (PLT) < 50,000/μL; Serum creatinine > 1.8 mg/dL or eGFR (or GFR) < 30 mL/min/1.7 m2; AST and ALT > 2.5 x upper limit of normal (ULN) (however, for a patient whose hepatic metastasis has been confirmed, AST and ALT > 5 x ULN). Subjects who are suffering from active infectious disease at screening and determined unfit to participate in this study; Subjects with solid tumors other than prostate cancer or hematologic malignancies including lymphoma within 3 years prior to screening (however, they can be enrolled in the case of properly treated non-melanoma skin cancer) Subjects who received gamma-emitting radioactive isotopes of high energy (> 300 keV) within the period 5 times longer than the half-life of this investigational product (about 10 hours) prior to screening Subjects with hypersensitivity to radioisotopes Subjects who participate in other clinical studies that may affect image obtainment from [18F]Florastamin-PET/CT or safety evaluation following IV injection of [18F]Florastamin from the time of enrollment for this study until the end (however, they can be enrolled if participating in a cohort clinical study conducted mainly through simple follow-up without administration of IP from the time of enrollment for the study until the end) Subjects who cannot undergo necessary imaging examinations due to medical conditions or other conditions (serious claustrophobia, radiophobia, etc.) that undermine the subject safety or compliance status for generating reliable data or completing the study in the principal investigator's judgment

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