Prostate Cancer
Conditions
Keywords
PSMA, PET, SPECT
Brief summary
Prostate cancer (PCa) is currently the most common cancer in men in Finland (www.cancerregistry.fi). Although prognosis is very good in majority of men, it is noteworthy that still up to 20% of PCa cases are metastatic at the time of initial diagnosis and yearly 900 men die because of prostate cancer. Robust primary staging is, therefore, one of the most important prognostic factors, and it is crucial for treatment decision. Despite their low sensitivity to detect metastasis, bone scintigraphy (BS) and contrast enhanced whole body computed tomography (ce-wbCT) are recommended by current guidelines for primary staging in men at risk of metastasis. MIP-1404 is a small-molecule PSMA inhibitor that can be used in SPECT systems (99mTc-MIP- 1404 SPECT/CT). 99mTc-MIP-1404 SPECT/CT is performed by a single IV bolus of 99mTc-MIP-1404, which binds with high affinity to extracellular domain of PSMA molecule. As of March 2020, a total of 629 subjects have received 99mTc-MIP-1404 injection averaging 740 ±111 MBq (20 ± 3 mCi) per administration in prospective clinical trials. 99mTc MIP-1404 has been well tolerated following a single IV dose at 740 ± 111 MBq in both healthy volunteers and patients with confirmed metastatic prostate adenocarcinoma. In prospective and retrospective studies, it has shown high potential to detect prostate cancer lesions in primary staging. In fact, Goffin et al. reported a sensitivity of 50% and specificity of 87% detecting local lymph node metastasis in radically operated patients when histopathology was used as a reference. This corresponds closely to the sensitivity of PSMA-PET. PROSTAMIP is a randomized prospective single-institutional study to demonstrate superiority of 99mTc-MIP-1404 SPECT/CT compared to traditional imaging modalities (99mTc-HMDP planar BS plus ce-wbCT).
Interventions
DIAGNOSTIC_TESTPSMA-imaging
Subjects undergo additional imaging i.e. PSMA/SPECT/CT and PSMA/PET/CT
Sponsors
Turku University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must be able and willing to give written informed consent and to comply with the requirements of this study protocol * Subjects must be male, aged 18 years or above at Baseline * Histopathologically confirmed high risk (Gleason ≥4+4, PSA ≥20 and/ or cT≥3a) acinar or ductal adenocarcinoma of prostate
Exclusion criteria
* Allergy/sensitivity to study medications or their ingredients * Subjects unable to provide written informed consent * Subjects who have any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk by participation in the study, or may influence the result of the study. * Subjects who have a history of drug or alcohol use that, in the opinion of the investigator, would interfere with adherence to study requirements. * Subjects who have androgen deprivation therapy initiated before enrolment * Subjects who have claustrophobia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with local lymph node metastasi(e)s | Baseline | Superiority of experimental arm (99mTc-MIP-1404 SPECT/CT) in detecting subjects with local lymph node metastasi(e)s compared to control arm (ce-wbCT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| False negative rate in lesion level between PSMA-SPECT/CT and conventional imaging | Baseline | Description of false negative rate of metastatic lesions between PSMA-SPECT/CT and conventional imaging (a combination of 99mTc-HMDP planar bone scintigraphy and contrast enhanced) |
| False positive rate in lesion level between PSMA-SPECT/CT and PSMA-PET/CT | Baseline | Description of false positive rate of metastatic lesions between PSMA-SPECT/CT and PSMA-PET/CT |
| False negative rate in lesion level between PSMA-SPECT/CT and PSMA-PET/CT | Baseline | Description of false negative rate of metastatic lesions between PSMA-SPECT/CT and PSMA-PET/CT |
| Inter-rater agreement | Baseline | Cohen´s Kappa value between the two readers in each imaging modality |
| Effect on treatment decision | Baseline | The number and proportion of subjects in which treatment recommendation was changed due to 99mTc-MIP 1404 SPECT/CT or 18F-PSMA-1007 PET/CT |
| Number of subjects with metastasis | Baseline | Comparison of detection of metastatic subjects (local lymph node metastasis and/ or distant metastasis) in experimental arm (99mTc-MIP-1404 SPECT/CT) and in control arm (a combination of 99mTc-HMDP planar bone scintigraphy and contract enhanced CT) |
| Diagnostic accuracy of detecting subjects with metastasis between PSMA-SPECT/CT and conventional imaging | Baseline | Comparison of diagnostic accuracy between PSMA-SPECT/CT and conventional imaging (a combination of 99mTc-HMDP planar BS and ce-wbCT) in detection of metastatic subjects (a combination of nodal and distant metastasis) |
| True positive rate in lesion level between PSMA-SPECT/CT and conventional imaging | Baseline | Description of true positive rate of metastatic lesions between PSMA-SPECT/CT and conventional imaging (a combination of 99mTc-HMDP planar bone scintigraphy and contrast enhanced) |
| False positive rate in lesion level between PSMA-SPECT/CT and conventional imaging | Baseline | Description of false positive rate of metastatic lesions between PSMA-SPECT/CT and conventional imaging (a combination of 99mTc-HMDP planar bone scintigraphy and contrast enhanced) |
| Diagnostic accuracy of detecting subjects with metastasis between PSMA-SPECT/CT and PSMA-PET/CT | Baseline | Comparison of diagnostic accuracy between PSMA-SPECT/CT and PSMA-PET/CT in detection of metastatic subjects (a combination of nodal and distant metastasis) |
| True positive rate in lesion level between PSMA-SPECT/CT and PSMA-PET/CT | Baseline | Description of true positive rate of metastatic lesions between PSMA-SPECT/CT and PSMA-PET/CT |
Other
| Measure | Time frame | Description |
|---|---|---|
| Gut microbiota | Baseline | Comparison results of shotgun metagenomic analysis of gut microbiota between non-metastatic patients, patients with PSMA only lesions and patients with lesions seen in conventional imaging |
| Optimization of 99mTc-MIP-1404 SPECT/CT imaging protocol | Baseline | The shortest acquisition time with acceptable decrease in diagnostic accuracy of detecting local lymph node metastases. |
| PSMA only lesions | Baseline | Characterization of PSMA only lesions |
| ctDNA | Baseline | Comparison ctDNA between non-metastatic patients, patients with PSMA only lesions and patients with lesions seen in conventional imaging |
Countries
Finland
Outcome results
None listed