A Phase 2 Study With MIP-1404 in Men With High-Risk PC Scheduled for RP and EPLND Compared to Histopathology

A Phase 2 Assessment of the Diagnostic Accuracy of 99mTc-MIP-1404 Imaging in Men With High-Risk Prostate Cancer Scheduled for Radical Prostatectomy (RP) and Extended Pelvic Lymph Node Dissection (EPLND) Compared to Histopathology

This was a multicenter, multi-reader, open-label, Phase 2 study assessing the safety and performance characteristics of MIP 1404 imaging in the detection of prostate gland and pelvic lymph node cancer. Comparative performance characteristics between MIP 1404 imaging and MRI were also assessed, as judged by histopathology results.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Drug: 99mTc-MIP-1404

Detailed Description

This is a single arm, open label study of approximately 100 high-risk prostate cancer patients scheduled for prostatectomy and extended pelvic lymph node dissection. Patients receive a single IV dose of 99mTc-MIP-1404 (study drug) followed by SPECT/CT scan 3-6 hours after injection. As standard of care, patients will undergo prostatectomy and extended pelvic lymph node dissection (EPLND) within three weeks of study drug dosing. 99mTc-MIP-1404 image data will be evaluated for visible uptake and compared with histopathology.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • University Hospitals Leuven
• Czech Republic
  • Olomouc, Czech Republic, 779 00
    • University Hospital Olomouc, Clinic of Urology
  • Plzen, Czech Republic, 30599
    • University Hospital Plzen, Department of Urology
  • Prague, Czech Republic, 128 08
    • General University Hospital in Prague, Clinic of Urology
  • Prague, Czech Republic, 140 59
    • Thomayer's Hospital
  • Prague, Czech Republic, 15006
    • University Hospital Motol, Clinic of Urology
  • Prague, Czech Republic, 180 01
    • Hospital Na Bulovce, Department of Urology
• Hungary
  • Budapest, Hungary, 8991
    • Bajcsy-Zsilinszky Hospital, Department of Urology
  • Budapest, Hungary, H-1076
    • Peterfy Sandor Street Hospital, Department of Urology
  • Budapest, Hungary, H1204
    • Jahn Ferenc South Pest Hospital, Department of Urology
• Italy
  • Milan, Italy, 20132
    • Vita-Salute University San Raffaele
  • Torino, Italy, 10126
    • University of Turin
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • UMC St. Radboud Nijmegen
• Poland
  • Gdansk, Poland, 80952
    • University Clinical Centre, Department of Urology
  • Warsaw, Poland, 00909
    • University Hospital Plzen, Department of Urology
  • Wroclaw, Poland, 50981
    • 4th Military Teaching Hospital and Polyclinic,
  • Wroclaw, Poland, 51124
    • "Provincial Specialist Hospital in Wroclaw, Department of Urology
• Russian Federation
  • Moscow, Russian Federation, 105077
    • City Clinical Hospital # 57
  • Moscow, Russian Federation, 115478
    • Federal Public State Institution "Russian Oncology Research Center n.a. N.N. Blokhin under the Russian Academy of medical sciences"
  • Moscow, Russian Federation, 125284
    • Moscow Oncology Research Institute n.a. P.A. Hertsen
  • Obninsk, Russian Federation, 249036
    • Federal State Public Institution "Medical Radiology Research Center" of Healthcare Ministry and Social Development of Russian Federation
  • Saint-Petersburg, Russian Federation, 197374
    • All-Russia Centre for Urgent Care and Radiation Medicine named after A.M. Nikiforov under the Ministry of the Russian Federation for Civil Defence, Emergencies and Elimination of Consequences of Natural Disasters
  • Saint-Petersburg, Russian Federation, 197758
    • Federal State Public Institution Russian Research center for Radiology and Surgical Technologies under the Federal agency for High-tech medical care
  • Saint-Petersburg, Russian Federation, 197758
    • Research Institute of Oncology n.a. Professor N.N. Petrov under the Federal Agency for Healthcare and Social Development
  • Saint-Petersburg, Russian Federation, 198255
    • St. Petersburg State Public Medical Institution: "Clinical Oncological Center"
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York City, New York, United States, 10021
      • New York Presbyterian Hospital - Cornell
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Glickman Urology & Kidney Institute, Cleveland Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University / Jefferson Urology Associates
  • South Carolina
    • Charleston, South Carolina, United States, 29435
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Vanguard Urologic Research Foundation
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington School of Medicine
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male aged 21 years or older.
• Ability to provide signed informed consent and willingness to comply with protocol requirements.
• Biopsy confirmed presence of adenocarcinoma of the prostate gland.
• At high-risk for metastatic disease by a stage of cT3, cT4, or a total nomogram score of greater than or equal to 130.
• Scheduled to undergo radical prostatectomy with extended pelvic lymph node dissection.
• Agree to use an acceptable form of birth control for a period of 7 days after the 99mTc MIP-1404 injection.

Exclusion Criteria:

• Participating would significantly delay the scheduled standard of care therapy.
• Administered a radioisotope within 5 physical half lives prior to study drug injection.
• Have any medical condition or other circumstances that, in the opinion of the investigator, would significantly decrease obtaining reliable data, achieving study objectives or completing the study.
• Have a contraindication for MR imaging.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug: 99mTc-MIP-1404; 20 ±3 mCi intravenous (IV) injection of 99mTc-MIP-1404	Drug: Drug: 99mTc-MIP-1404; A single dose of 20 ±3 mCi intravenous (IV) injection of 99mTc-MIP-1404; Other Names: MIP-1404

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the Ability of 99mTc-MIP-1404 to Detect Prostate Cancer Within the Prostate Gland.	For the prostate gland, sensitivity values refer to the number of subjects in the study, i.e., the percentages of true positive subjects correctly identified by the imaging technique. Pathology results were used as the truth standard for all imaging analyses.	Within 3-6 hours of dosing SPECT/CT images will be taken

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the Ability of MIP-1404 to Detect Metastatic Prostate Cancer Within Pelvic Lymph Nodes	For lymph nodes, sensitivity values refer to the number of subjects in the study, i.e., the percentages of true positive subjects correctly identified by the imaging technique. Pathology results were used as the truth standard for all imaging analyses.	Within 3-6 hours of dosing SPECT/CT images will be taken
Assess the Ability of MIP-1404 to Detect the Extent and Location of Prostate Cancer Within the Prostate Gland	For specific segments of the prostate, a sensitivity value refers to the number of evaluable segments (histologically examined "tissue-segments") from all subjects, i.e., the percentages of true positive segments correctly identified by the imaging technique.	Within 3-6 hours of dosing SPECT/CT images will be taken
Assess the Ability of MIP-1404 to Detect the Specific Location of Metastatic Prostate Cancer Within Anatomic Pelvic Lymph Node Regions	For specific segments of the lymph nodes, a sensitivity value refers to the number of evaluable segments (histologically examined "tissue-segments") from all subjects, i.e., the percentages of true positive segments correctly identified by the imaging technique.	Within 3-6 hours of dosing SPECT/CT images will be taken
Assess the Comparative Performance of MIP-1404 Against MRI for Detection of Prostate Cancer Within the Prostate Gland.	Comparative performance characteristics between MIP-1404 imaging and MRI were analyzed for the prostate gland. MIP-1404 and MRI sensitivities were derived from case positive histopathology results.	Within 3-6 hours of dosing SPECT/CT images will be taken
Assess the Comparative Performance of MIP-1404 Against MRI for Detection of Metastatic Prostate Cancer Within Pelvic Lymph Nodes.	Comparative performance characteristics between MIP-1404 imaging and MRI were analyzed for the lymph nodes. MIP-1404 and MRI sensitivities were derived from case positive histopathology results.	Within 3-6 hours of dosing SPECT/CT images will be taken

Collaborators and Investigators

• Sponsor: Molecular Insight Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Douglas Scherr, M.D., New York Presbyterian Hospital-Cornell; Principal Investigator: Jeffrey Karnes, MD, Mayo Clinic; Principal Investigator: Kevin Slawin, MD, University of Texas Vanguard Urologic Research Foundation; Principal Investigator: Thomas Keane, MD, Medical University of South Carolina; Principal Investigator: Edouard Trabulsi, MD, Thomas Jefferson University / Jefferson Urology Associates; Principal Investigator: David Jarrard, MD, University of Wisconsin, Madison; Principal Investigator: William Ellis, MD, University of Washington; Principal Investigator: Judd Moul, MD, Duke University; Principal Investigator: Eric Klein, MD, Glickman Urology & Kidney Institute, Cleveland Clinic; Principal Investigator: Bertram Yuh, MD, City of Hope National Cancer Center; Principal Investigator: Steven Joniau, MD, Universitaire Ziekenhuizen KU Leuven; Principal Investigator: Alberto Briganti, MD, Vita-Salute University San Raffaele; Principal Investigator: Paolo Gontero, MD, University of Turin, Italy; Principal Investigator: Mikhail I Shkolnik, MD, Federal State Public Institution Russian Research center for Radiology and Surgical Technologies under the Federal agency for High-tech medical care; Principal Investigator: Petr A Karlov, MD, St. Petersburg State Public Medical Institution: "Clinical Oncological Center"; Principal Investigator: Vsevolod B Matveev, MD, Federal Public State Institution "Russian Oncology Research Center n.a. N.N. Blokhin under the Russian Academy of medical sciences"; Principal Investigator: Boris Ya Alexeev, MD, Moscow Oncology Research Institute n.a. P.A. Hertsen; Principal Investigator: Sergey V Mishugin, MD, City Clinical Hospital # 57; Principal Investigator: Oleg B Karyakin, Federal State Public Institution "Medical Radiology Research Center" of Healthcare Ministry and Social Development of Russian Federation; Principal Investigator: Alexander K Nosov, MD, Research Institute of Oncology n.a. Professor N.N. Petrov under the Federal Agency for Healthcare and Social Development; Principal Investigator: Sergey B Petrov, MD, All-Russia Centre for Urgent Care and Radiation Medicine named after A.M. Nikiforov under the Ministry of the Russian Federation for Civil Defence, Emergencies and Elimination of Consequences of Natural Disasters; Principal Investigator: Milan Hora, MD, PhD, University Hospital Plzen, Department of Urology; Principal Investigator: Josef Stolz, MD, University Hospital Motol, Clinic of Urology; Principal Investigator: Vladimir Student, MD, PhD, University Hospital Olomouc, Clinic of Urology; Principal Investigator: Marek Krolupper, MD, Hospital Na Bulovce, Department of Urology; Principal Investigator: Michael Pesl,, MD, General University Hospital in Prague, Clinic of Urology; Principal Investigator: Roman Zachoval,, MD, PhD, MBA, Thomayer's Hospital; Principal Investigator: Marcin Matuszewski, MD, PhD, University Clinical Centre, Department of Urology; Principal Investigator: Henryk Zielinski, MD, University Hospital Plzen, Department of Urology; Principal Investigator: Jerzy Sokolowski, MD, PhD, Provincial Specialist Hospital in Wroclaw, Department of Urology; Principal Investigator: Tomasz Szydelko, MD, PhD, 4th Military Teaching Hospital and Polyclinic,; Principal Investigator: Geza Boszormenyi-Nagy, MD, Bajcsy-Zsilinszky Hospital, Department of Urology; Principal Investigator: Peter Tenke, MD, Jahn Ferenc South Pest Hospital, Department of Urology; Principal Investigator: Istvan Buzogany, MD, Peterfy Sandor Street Hospital, Department of Urology; Principal Investigator: Michiel Sedelaar, MD, UMC St. Radboud Nijmegen

Publications and helpful links

General Publications

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• Perner S, Hofer MD, Kim R, Shah RB, Li H, Moller P, Hautmann RE, Gschwend JE, Kuefer R, Rubin MA. Prostate-specific membrane antigen expression as a predictor of prostate cancer progression. Hum Pathol. 2007 May;38(5):696-701. doi: 10.1016/j.humpath.2006.11.012. Epub 2007 Feb 22.
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• Troyer JK, Beckett ML, Wright GL Jr. Detection and characterization of the prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids. Int J Cancer. 1995 Sep 4;62(5):552-8. doi: 10.1002/ijc.2910620511.
• Chang SS, Reuter VE, Heston WD, Bander NH, Grauer LS, Gaudin PB. Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer Res. 1999 Jul 1;59(13):3192-8.
• Maresca KP, Hillier SM, Femia FJ, Keith D, Barone C, Joyal JL, Zimmerman CN, Kozikowski AP, Barrett JA, Eckelman WC, Babich JW. A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer. J Med Chem. 2009 Jan 22;52(2):347-57. doi: 10.1021/jm800994j.
• Godoy G, Chong KT, Cronin A, Vickers A, Laudone V, Touijer K, Guillonneau B, Eastham JA, Scardino PT, Coleman JA. Extent of pelvic lymph node dissection and the impact of standard template dissection on nomogram prediction of lymph node involvement. Eur Urol. 2011 Aug;60(2):195-201. doi: 10.1016/j.eururo.2011.01.016. Epub 2011 Jan 18.
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Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: August 13, 2012
• First Submitted That Met QC Criteria: August 15, 2012
• First Posted (Estimate): August 17, 2012

Study Record Updates

• Last Update Posted (Estimate): February 7, 2017
• Last Update Submitted That Met QC Criteria: December 14, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: NEWLY DIAGNOSED; PROSTATE CANCER; HIGH-RISK; PROSTATECTOMY SURGERY
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: MIP-1404-201