99mTc-MIP-1404 SPECT/CT in Primary Staging of Prostate Cancer

99mTc-MIP-1404 SPECT/CT for Primary PROstate Cancer STAging: Comparative Prospective, Randomized Trial to Present Guideline Imaging

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).

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Diagnostic test: PSMA-imaging

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Southwest Finland
    • Turku, Southwest Finland, Finland, 20521
      • Recruiting
      • University Hospital of Turku, Hospital Distric of Southwest Finland
      • Contact: Otto O Ettala, MD, PhD; Phone Number: +358 23130280; Email: otto.ettala@varha.fi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control arm; Subjects undergo bone scintigraphy and whole body CT
Experimental: Experimental arm; Subjects undergo bone scintigraphy, whole body CT, 99mTc-MIP-1404 SPECT/CT, and 18F- PSMA-1007 PET/CT	Diagnostic test: PSMA-imaging; Subjects undergo additional imaging i.e. PSMA/SPECT/CT and PSMA/PET/CT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with local lymph node metastasi(e)s	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)	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with metastasis	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)	Baseline
Diagnostic accuracy of detecting subjects with metastasis between PSMA-SPECT/CT and conventional imaging	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)	Baseline
True positive rate in lesion level between PSMA-SPECT/CT and conventional imaging	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)	Baseline
False positive rate in lesion level between PSMA-SPECT/CT and conventional imaging	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)	Baseline
False negative rate in lesion level between PSMA-SPECT/CT and conventional imaging	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)	Baseline
Diagnostic accuracy of detecting subjects with metastasis between PSMA-SPECT/CT and PSMA-PET/CT	Comparison of diagnostic accuracy between PSMA-SPECT/CT and PSMA-PET/CT in detection of metastatic subjects (a combination of nodal and distant metastasis)	Baseline
True positive rate in lesion level between PSMA-SPECT/CT and PSMA-PET/CT	Description of true positive rate of metastatic lesions between PSMA-SPECT/CT and PSMA-PET/CT	Baseline
False positive rate in lesion level between PSMA-SPECT/CT and PSMA-PET/CT	Description of false positive rate of metastatic lesions between PSMA-SPECT/CT and PSMA-PET/CT	Baseline
False negative rate in lesion level between PSMA-SPECT/CT and PSMA-PET/CT	Description of false negative rate of metastatic lesions between PSMA-SPECT/CT and PSMA-PET/CT	Baseline
Inter-rater agreement	Cohen´s Kappa value between the two readers in each imaging modality	Baseline
Effect on treatment decision	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	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSMA only lesions	Characterization of PSMA only lesions	Baseline
ctDNA	Comparison ctDNA between non-metastatic patients, patients with PSMA only lesions and patients with lesions seen in conventional imaging	Baseline
Gut microbiota	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	Baseline
Optimization of 99mTc-MIP-1404 SPECT/CT imaging protocol	The shortest acquisition time with acceptable decrease in diagnostic accuracy of detecting local lymph node metastases.	Baseline

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Investigators: Principal Investigator: Otto O Ettala, Turku University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 3, 2023
• First Submitted That Met QC Criteria: January 12, 2024
• First Posted (Actual): January 23, 2024

Study Record Updates

• Last Update Posted (Actual): January 23, 2024
• Last Update Submitted That Met QC Criteria: January 12, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: PET; PSMA; SPECT
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: T19/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No