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

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01667536
• Other study ID #: MIP-1404-201
• Status: Active, not recruiting
• Phase: Phase 2
• First received: August 13, 2012
• Last updated: November 12, 2013
• Start date: August 2012
• Est. completion date: December 2013

Study information

• Verified date: November 2013
• Source: Molecular Insight Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 21 Years and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Drug: 99mTc-MIP-1404
A single dose of 20 ±3 mCi intravenous (IV) injection of 99mTc-MIP-1404

Locations

Country	Name	City	State
Belgium	University Hospitals Leuven	Leuven
Czech Republic	University Hospital Olomouc, Clinic of Urology	Olomouc
Czech Republic	University Hospital Plzen, Department of Urology	Plzen
Czech Republic	General University Hospital in Prague, Clinic of Urology	Prague
Czech Republic	Hospital Na Bulovce, Department of Urology	Prague
Czech Republic	Thomayer's Hospital	Prague
Czech Republic	University Hospital Motol, Clinic of Urology	Prague
Hungary	Bajcsy-Zsilinszky Hospital, Department of Urology	Budapest
Hungary	Jahn Ferenc South Pest Hospital, Department of Urology	Budapest
Hungary	Peterfy Sandor Street Hospital, Department of Urology	Budapest
Italy	Vita-Salute University San Raffaele	Milan
Italy	University of Turin	Torino
Netherlands	UMC St. Radboud Nijmegen	Nijmegen
Poland	University Clinical Centre, Department of Urology	Gdansk
Poland	University Hospital Plzen, Department of Urology	Warsaw
Poland	"Provincial Specialist Hospital in Wroclaw, Department of Urology	Wroclaw
Poland	4th Military Teaching Hospital and Polyclinic,	Wroclaw
Russian Federation	City Clinical Hospital # 57	Moscow
Russian Federation	Federal Public State Institution "Russian Oncology Research Center n.a. N.N. Blokhin under the Russian Academy of medical sciences"	Moscow
Russian Federation	Moscow Oncology Research Institute n.a. P.A. Hertsen	Moscow
Russian Federation	Federal State Public Institution "Medical Radiology Research Center" of Healthcare Ministry and Social Development of Russian Federation	Obninsk
Russian Federation	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	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	Research Institute of Oncology n.a. Professor N.N. Petrov under the Federal Agency for Healthcare and Social Development	Saint-Petersburg
Russian Federation	St. Petersburg State Public Medical Institution: "Clinical Oncological Center"	Saint-Petersburg
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Glickman Urology & Kidney Institute, Cleveland Clinic	Cleveland	Ohio
United States	City of Hope National Cancer Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Texas Vanguard Urologic Research Foundation	Houston	Texas
United States	University of Wisconsin	Madison	Wisconsin
United States	New York Presbyterian Hospital - Cornell	New York City	New York
United States	Thomas Jefferson University / Jefferson Urology Associates	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Washington School of Medicine	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Molecular Insight Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Czech Republic,  Hungary,  Italy,  Netherlands,  Poland,  Russian Federation, 

References & Publications (18)

American Cancer Society, Inc., Surveillance Research; Cancer Facts & Figures, 2012

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Durkalski VL, Palesch YY, Lipsitz SR, Rust PF. Analysis of clustered matched-pair data for a non-inferiority study design. Stat Med. 2003 Jan 30;22(2):279-90. — View Citation

Ghosh A, Heston WD. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J Cell Biochem. 2004 Feb 15;91(3):528-39. Review. — View Citation

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. — View Citation

Hillier SM, Maresca KP, Femia FJ, Marquis JC, Foss CA, Nguyen N, Zimmerman CN, Barrett JA, Eckelman WC, Pomper MG, Joyal JL, Babich JW. Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer. Cancer Res. 2009 Sep 1;69(17):6932-40. doi: 10.1158/0008-5472.CAN-09-1682. Epub 2009 Aug 25. — View Citation

Hövels AM, Heesakkers RA, Adang EM, Jager GJ, Strum S, Hoogeveen YL, Severens JL, Barentsz JO. The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis. Clin Radiol. 2008 Apr;63(4):387-95. doi: 10.1016/j.crad.2007.05.022. Epub 2008 Feb 4. Review. — View Citation

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Kinoshita Y, Kuratsukuri K, Landas S, Imaida K, Rovito PM Jr, Wang CY, Haas GP. Expression of prostate-specific membrane antigen in normal and malignant human tissues. World J Surg. 2006 Apr;30(4):628-36. — View Citation

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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. — View Citation

Murphy GP, Elgamal AA, Su SL, Bostwick DG, Holmes EH. Current evaluation of the tissue localization and diagnostic utility of prostate specific membrane antigen. Cancer. 1998 Dec 1;83(11):2259-69. Review. — View Citation

Perner S, Hofer MD, Kim R, Shah RB, Li H, Möller 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. Epub 2007 Feb 22. — View Citation

Pinto JT, Suffoletto BP, Berzin TM, Qiao CH, Lin S, Tong WP, May F, Mukherjee B, Heston WD. Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells. Clin Cancer Res. 1996 Sep;2(9):1445-51. — View Citation

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Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res. 1997 Jan;3(1):81-5. — View Citation

Smith-Jones PM, Vallabahajosula S, Goldsmith SJ, Navarro V, Hunter CJ, Bastidas D, Bander NH. In vitro characterization of radiolabeled monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen. Cancer Res. 2000 Sep 15;60(18):5237-43. — View Citation

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* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	PSMA expression relative to 99mTc-MIP-1404 imaging in a sub-set of surgical specimens.	This is an exploratory objective in which PSMA staining will be conducted on a sub-set of patients' surgical specimens. To minimize variability PSMA staining will be analyzed centrally post-enrollment completion with all specimens included to be stained at the same time.	PSMA expression analysis will be conducted upon completion of enrollment	No
Other	Compare performance of 99mTc-MIP-1404 against MRI for detection of the extent and location of prostate cancer within the prostate gland.	To obtain MRI images (pre-dose) and 99m1404 SPECT/CT images (post-dose) for comparison.	The MRI will take place at Screening. SPECT/CT imaging will take place within 3-6 hours of dosing	No
Primary	Ability of 99mTc-MIP-1404 to detect prostate cancer within the prostate gland.	Tissue distribution of 99mTc-MIP-1404 SPECT/CT imaging in tumor and non-tumorous regions of the prostate and pelvic lymph nodes(as determined by histopathology) in patients undergoing standard of care prostatectomy with extended pelvic lymph node dissection. Pathology results will be used as the truth standard for all imaging analyses.	Within 3-6 hours of dosing SPECT/CT images will be taken	No
Primary	Clinical safety of 99mTc-MIP-1404	Clinical laboratory tests will include hematology, clinical chemistry, and PSA. Vital signs will include heart rate and blood pressure.	Vital signs will be taken at Pre-Dose and Post-Dose as well as between 3-6 hours post-dose. Lab samples: will be taken at Screening and Pre-Surgery (within 21 days of dosing)	Yes
Secondary	Ability of 99mTc-MIP-1404 to detect the extent and location of prostate cancer within the prostate gland.	Tissue distribution of 99mTc-MIP-1404 SPECT/CT imaging in tumor and non-tumorous regions of the prostate (as determined by histopathology) in patients undergoing standard of care prostatectomy	Within 3-6 hours of dosing SPECT/CT images will be taken	No
Secondary	Ability of 99mTc-MIP-1404 to detect metastatic prostate cancer within pelvic lymph nodes.	To obtain tissue distribution of 99mTc-MIP-1404 SPECT/CT imaging in tumor and non-tumorous regions of pelvic lymph nodes	Within 3-6 hours of dosing SPECT/CT images will be taken	No
Secondary	Ability of 99mTc-MIP-1404 to detect the specific location of metastatic prostate cancer within anatomic pelvic lymph node regions.	To obtain tissue distribution of 99mTc-MIP-1404 SPECT/CT imaging in tumor and non-tumorous regions of pelvic lymph nodes	Within 3-6 hours of dosing SPECT/CT images will be taken	No
Secondary	Compare performance of 99mTc-MIP-1404 against MRI for detection of prostate cancer within the prostate gland.	To obtain MRI images (pre-dose) and 99m1404 SPECT/CT images (post-dose) for comparison.	The MRI will take place at Screening. SPECT/CT imaging will take place within 3-6 hours of dosing	No
Secondary	Compare performance of 99mTc-MIP-1404 against MRI for detection of metastatic prostate cancer within pelvic lymph nodes.	To obtain MRI images (pre-dose) and 99m1404 SPECT/CT images (post-dose) for comparison.	The MRI will take place at Screening. SPECT/CT imaging will take place within 3-6 hours of dosing	No