Gadoxetate Enhanced Imaging Study to Detect Prostate Cancer

• ClinicalTrials.gov Identifier: NCT01867424
• Recruitment Status: Completed
• First Posted: June 4, 2013
• Results First Posted: March 20, 2018
• Last Update Posted: July 8, 2020
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Ismail B. Turkbey, National Cancer Institute (NCI)

Study Description

Brief Summary:

Background:

- Prostate cancer is the most common cancer type among men. Some prostate cancers respond to hormonal therapy. However, some cell characteristics of other prostate cancers cause it not to respond as well to these therapies. Researchers want to see if gadoxetate, a contrast agent used to help identify damaged liver tissue, can help tell these types of prostate cancer apart. It may be able to identify if a man has a type of prostate cancer for which hormone therapy may not work as well.

Objectives:

- To see if gadoxetate can help identify different types of prostate cancers during imaging studies.

Eligibility:

- Men at least 18 years of age who have prostate cancer. Participants will be having surgery to either remove the prostate or take tumor tissue samples.

Design:

• Participants will be screened with a physical exam and medical history. Blood samples will be collected.
• Participants will have a magnetic resonance imaging (MRI) scan of the lower torso. They will receive gadoxetate during the MRI scan.
• Participants who have surgery will have a sample of their tumor cells collected. Those who have a biopsy will provide cells from this biopsy for study.
• Treatment will not be provided as part of this study.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Eovist	Phase 2

Detailed Description:

BACKGROUND:

• Prostate cancer is the most common non-cutaneous malignancy among men in the western world. Prognostic biomarkers would be useful in stratifying patients to different treatments.
• The expression of a testosterone membrane transporter, organic anion-transporting polypeptide 1B3 (OATP1B3), is associated with shorter time to progression after hormonal ablation therapy and shorter overall survival in prostate cancer patients. 52% of localized prostate cancer lesions express OATP1B3, while 92% of prostate cancer metastases requiring hormonal ablation treatment, express OATP1B3 in soft tissue lesions. Expression of OATP1B3 also correlates with Gleason grade.
• Current imaging methods cannot predict treatment failure or resistance.
• Gadoxetate disodium (Gd-EOB-DTPA) (Eovist , Bayer HealthCare Pharmaceuticals Inc. Pittsburgh, PA) is an MR imaging agent which is FDA-approved gadolinium chelate for detecting hepatocellular carcinoma (HCC), as normal hepatocytes express OATP1B3 while most hepatocellular carcinomas (HCC) do not. However, those HCCs that do take up Eovist have been shown to express OATP1B3.
• Eovist may be useful to evaluate OATP1B3 status in patients with prostate cancer and may therefore serve as a prognostic and treatment biomarker.

PRIMARY OBJECTIVE:

-Evaluate the uptake and retention of Eovist in prostate cancers.

ELIGIBILTY:

• Male subjects greater than or equal to 18 years old
• Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2
• Subjects with clinically localized prostate cancer must have image guided biopsy confirmed prostate cancer and sufficient tissue available for OATP1B3 immunohistochemistry (IHC).
• Subjects with advanced disease who have failed hormone therapy and who have sufficient tissue from a soft tissue or metastatic bone lesion (measuring greater than or equal to1.5cm in diameter at computed tomography (CT) or magnetic resonance imaging (MRI) scan) available for OATP1B3 IHC.

or

-Subjects, for whom tissue is not available, must have a soft tissue or metastatic bone lesion that can be biopsied and be willing to undergo percutaneous biopsy to obtain tissue for OATP1B3 expression.

DESIGN:

• This pilot study will accrue 25 subjects divided into two arms: 10 evaluable subjects with localized prostate cancer and 15 evaluable subjects with advanced disease
• Each subject will receive a single intravenous (IV) dose of Eovist by bolus injection
• All subjects will undergo magnetic resonance imaging (MRI) prior to and immediately after, 10, 20 and 60 minutes post-Eovist injection

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Pilot Study of Eovist (Gadoxetate) Enhanced MRI for the Detection of Prostate Cancer
• Actual Study Start Date: May 14, 2013
• Actual Primary Completion Date: May 30, 2016
• Actual Study Completion Date: December 8, 2016

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Participants with Advanced Disease; Advanced disease: who have failed hormone therapy and who have sufficient tissue from a soft tissue or metastatic bone lesion (measuring 1.5cm in diameter at computed tomography (CT) or magnetic resonance imaging (MRI) scan) available for organic anion-transporting polypeptide 1B3 (OATP1B3) immunohistochemistry (IHC) or must have a soft tissue or metastatic bone lesion that can be biopsied and be willing to undergo percutaneous biopsy to obtain tissue for OATP1B3 expression.	Drug: Eovist; 0.1 ml/kg Eovist will be administered intravenous (IV) to each patient
Active Comparator: Participants with Localized Disease; Localized disease: must have image guided biopsy confirmed prostate cancer and sufficient tissue available for OATP1B3 IHC.	Drug: Eovist; 0.1 ml/kg Eovist will be administered intravenous (IV) to each patient

Outcome Measures

Primary Outcome Measures :

1. Uptake and Retention of Eovist in Prostate Cancers [ Time Frame: Baseline and 20 minutes, 40 minutes, and 60 minutes after Eovist injection ]
   Uptake and retention of Eovist in prostate cancers is measured by the change of magnetic resonance imaging (MRI) parameter values between pre and post injection.

Secondary Outcome Measures :

1. Number of Participants Who Were Evaluated for Magnetic Resonance (MR) Contrast Enhancement Parameters Following Eovist Injection With Respect to Gleason Score [ Time Frame: At baseline ]
   Scans with or without endorectal coil were obtained through the prostate gland, bone metastasis or soft tissue metastasis (usually a lymph node) selected as the target lesion as described in primary outcome measure. Then 0.1 ml/kg Eovist was administered intravenously. Scans were correlated with baseline Gleason score obtained from the prostate biopsy. Gleason score <7 = low grade cancer; Gleason score ≥7 = high grade cancer.
2. Baseline Serum Prostate-Specific Antigen (PSA) Levels of Patients Who Were Evaluated for Magnetic Resonance (MR) Contrast Enhancement Parameters Following Eovist Injection [ Time Frame: Baseline ]
   Scans with or without endorectal coil were obtained through the prostate gland, bone metastasis or soft tissue metastasis (usually a lymph node) selected as the target lesion as described in primary outcome measure. Then 0.1 ml/kg Eovist was administered intravenously. Scans were correlated to baseline PSA levels.
3. Number of Participants With Serious and Non-serious Adverse Events [ Time Frame: From date treatment consent signed to date off study, approximately 3 years and 33 days ]
   Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes

Gender Eligibility Description

2.1.1.1 Subject is greater than or equal to 18 years old.

2.1.1.2 Subjects with clinically localized prostate cancer (outside pathology is acceptable) must have image guided biopsy confirmed prostate cancer and sufficient tissue available (obtained before or after 20 weeks of Eovist injection) for organic anion-transporting polypeptide 1B3 (OATP1B3) expression.

2.1.1.3 Subjects with advanced disease who have failed hormone therapy and who have sufficient tissue (obtained before or after 20 weeks of Eovist injection) from a soft tissue lesion (measuring greater than or equal to 1.5cm in diameter at computed tomography (CT) or magnetic resonance imaging (MRI) scan) available for OATP1B3 expression.

or

2.1.1.4 Subjects, for whom tissue is not available, must have a soft tissue or metastatic bone lesion that can be biopsied and be willing to undergo percutaneous biopsy to obtain tissue for OATP1B3 expression.

• Accepts Healthy Volunteers: No

Criteria

• INCLUSION CRITERIA:

2.1.1.1 Subject is greater than or equal to 18 years old.

2.1.1.2 Subjects with clinically localized prostate cancer (outside pathology is acceptable) must have image guided biopsy confirmed prostate cancer and sufficient tissue available (obtained before or after 20 weeks of Eovist injection) for organic anion-transporting polypeptide 1B3 (OATP1B3) expression.

2.1.1.3 Subjects with advanced disease who have failed hormone therapy and who have sufficient tissue (obtained before or after 20 weeks of Eovist injection) from a soft tissue lesion (measuring greater than or equal to 1.5cm in diameter at computed tomography (CT) or magnetic resonance imaging (MRI) scan) available for OATP1B3 expression.

or

2.1.1.4 Subjects, for whom tissue is not available, must have a soft tissue or metastatic bone lesion that can be biopsied and be willing to undergo percutaneous biopsy to obtain tissue for OATP1B3 expression.

2.1.1.5 Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

2.1.1.6 Serum creatinine within 3 weeks prior to Eovist MRI less than or equal to 1.8mg/dl and estimated glomerular filtration rate (eGFR) must be greater than 30 ml/min/1.73m(2).

2.1.1.7 Patients must have normal liver function as defined below:

• total bilirubin less than 2 times normal institutional limits or greater than 3.0 mg/dl in patients with Gilberts syndrome
• Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 times institutional upper limit of normal

2.1.1.8 Ability of subject to sign a written informed consent document

EXCLUSION CRITERIA:

2.1.2.1 Subjects with known hypersensitivity and allergy to gadolinium contrast agents

2.1.2.2 Subjects with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results

2.1.2.3 Subjects with severe claustrophobia unresponsive to oral anxiolytics

2.1.2.4 Subjects with contraindications to magnetic resonance imaging (MRI)

2.1.2.5 Subjects weighing greater than 136 kg (weight limit for scanner table)

2.1.2.6 Subjects with pacemakers, cerebral aneurysm clips, shrapnel injury, or other implanted electronic devices or metal not compatible with MRI

2.1.2.7 Subjects with other medical conditions deemed by the principle investigator (or associates) to make the subject ineligible for protocol procedures

2.1.2.8 Subjects who will have a delay in clinically indicated radiation therapy due to the interval between Eovist MRI imaging and biopsy

Contacts and Locations

Locations

United States, Maryland

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ismail B Turkbey, M.D.; National Cancer Institute (NCI)

  Study Documents (Full-Text)

Documents provided by Ismail B. Turkbey, National Cancer Institute (NCI):

Study Protocol, Statistical Analysis Plan, and Informed Consent Form  [PDF] May 12, 2015

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

Publications:

Narita M, Hatano E, Arizono S, Miyagawa-Hayashino A, Isoda H, Kitamura K, Taura K, Yasuchika K, Nitta T, Ikai I, Uemoto S. Expression of OATP1B3 determines uptake of Gd-EOB-DTPA in hepatocellular carcinoma. J Gastroenterol. 2009;44(7):793-8. doi: 10.1007/s00535-009-0056-4. Epub 2009 Apr 29.

Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300. doi: 10.3322/caac.20073. Epub 2010 Jul 7. Erratum In: CA Cancer J Clin. 2011 Mar-Apr;61(2):133-4.

Hamada A, Sissung T, Price DK, Danesi R, Chau CH, Sharifi N, Venzon D, Maeda K, Nagao K, Sparreboom A, Mitsuya H, Dahut WL, Figg WD. Effect of SLCO1B3 haplotype on testosterone transport and clinical outcome in caucasian patients with androgen-independent prostatic cancer. Clin Cancer Res. 2008 Jun 1;14(11):3312-8. doi: 10.1158/1078-0432.CCR-07-4118.

• Responsible Party: Ismail B. Turkbey, Principal Investigator, National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01867424
• Other Study ID Numbers: 130145; 13-C-0145
• First Posted: June 4, 2013
• Results First Posted: March 20, 2018
• Last Update Posted: July 8, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Ismail B. Turkbey, National Cancer Institute (NCI):

Testosterone Membrane Transporter; OATP1B3; Castration Resistant Prostate Cancer; Prostatectomy; Gadolinium-Based Contrast Agent

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases