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Virtual Histology of the Bladder Wall for Bladder Cancer Staging

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04369560
Recruitment Status : Recruiting
First Posted : April 30, 2020
Last Update Posted : September 21, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jodi Maranchie, University of Pittsburgh

Brief Summary:
This is a phase Ib study of the safety and performance of a novel intravesical contrast-enhanced Magnetic Resonance Imaging protocol for determination of bladder cancer stage prior to transurethral resection of bladder tumor (21 subjects) or prior to radical cystectomy for muscle invasive disease (21 subjects). Subjects will undergo a single MRI study: a pre-contrast, single breath hold image followed by sterile placement of a temporary urethral catheter for instillation of a 50mL solution containing Gadobutrol (4 mM) plus ferumoxytol (5 mM) and then a second, post-contrast image. Images will be reviewed by two dedicated abdominal radiologists, who are blinded to the pathologic staging, for determination of tumor presence and depth of bladder wall penetration.

Condition or disease Intervention/treatment Phase
Urinary Bladder Neoplasms Diagnostic Test: Magnetic Resonance Imaging Drug: Gadobutrol intravesical administration (4mM) Drug: Ferumoxytol intravesical administration (5 mM) Early Phase 1

Detailed Description:

Twenty one patients with at least one cystoscopically confirmed papillary bladder tumor, who have been scheduled for Transurethral Resection of Bladder Tumor (TURBT) for surgical extirpation and staging, and twenty-one patients with histologically confirmed, muscle invasive transitional cell carcinoma of the bladder who have been scheduled for definitive radical cystectomy with curative intent will be recruited for a single study Magnetic Resonance Imaging to be performed between 1 and 6 days prior to their scheduled procedure.

Magnetic Resonance Imaging of all the enrolled patients will be performed on a 60-cm, wide-bore, 3T scanner (Siemens AG, Erlangen, Germany) with a 32-channel pelvic phased-array coil placed over the bladder using radial k-space sampling technique for volumetric free breathing acquisition with NCM enhanced StarVIBE57. Un-enhanced fast spoiled gradient-echo images with fat suppression will be obtained prior aseptic instillation of 50cc of a novel contrast mixture (NCM) of Gadobutrol (4 mM) plus Ferumoxytol (5 mM) in sterile water through a temporary urethral catheter. The catheter will then be removed and the patient repositioned in the scanner to obtain post-contrast images. All the image datasets will be linearly registered to the subject to ensure that regions of interest represent the same anatomical location at all time points. Post-contrast T1, pre-contrast T1 and deltaT1 will be measured from the acquired images. Two radiologists blinded to the pathologic findings will evaluate the Magnetic Resonance images to assign a radiologic tumor stage that will be compared with the subsequent pathologic stage determined at time of surgery. Following the MRI study, subjects will proceed with their surgical procedure as scheduled per standard of care.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Diagnostic Test - Magnetic Resonance Imaging
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Virtual Histology of the Bladder Wall for Bladder Cancer Staging; A Novel Intravesical Contrast-Enhanced MRI for Bladder Cancer Staging
Estimated Study Start Date : September 2020
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Magnetic Resonance Imaging
Prior to planned surgical resection, subjects will undergo a single Magnetic Resonance Imaging study: a single breath-hold pre-contrast image followed by sterile placement of a temporary urethral catheter for instillation of a 50mL solution containing Gadobutrol (4 mM) plus ferumoxytol (5 mM) and a second, single breath hold post-contrast image.
Diagnostic Test: Magnetic Resonance Imaging
60-cm wide bore 3T scanner (Siemens AG, Erlangen, Germany) with a 32-channel pelvic phased-array coil placed over the bladder.

Drug: Gadobutrol intravesical administration (4mM)
A paramagnetic macrocyclic gadolinium-based contrast agent administered intravenously for use in magnetic resonance imaging. Contrast-enhancement is a result of the neutral complex of gadolinium and dihydroxy-hydroxymethylpropyl- tetraazacyclododecane-triacetic acid (butrol).
Other Name: Image result for other names for Gadobutrol Gadavist

Drug: Ferumoxytol intravesical administration (5 mM)
An iron preparation (Fe3O4) approved for intravenous treatment of anemia in the setting of renal failure, comprised of superparamagnetic iron oxide nanoparticles which are coated by a semi-synthetic carbohydrate shell in an isotonic, neutral pH solution.
Other Name: FERAHEME




Primary Outcome Measures :
  1. Accuracy of Magnetic Resonance Imaging assessment of depth of bladder wall penetration to predict pathologic stage determined at tumor resection [ Time Frame: 4 weeks ]
    The assessment of clinical tumor stage assigned by the radiologist will be compared to the stage reported by the clinical pathologist following tumor resection to determine the overall accuracy of MRI for bladder cancer staging.


Secondary Outcome Measures :
  1. Accuracy of Magnetic Resonance Imaging to detect residual/recurrent bladder tumor [ Time Frame: 4 weeks ]
    Patients are typically scheduled for radical cystectomy after initial TURBT with or without neoadjuvant chemotherapy. MRI findings of bladder tumor will be compared with the areas of tumor identified on whole mount sectioning of the bladder to estimate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI for bladder cancer. Receiver operating characteristic (ROC) curve analysis will be used to estimate the tumor size threshold value for the diagnosis with MRI.

  2. Rate of Adverse Events [ Time Frame: 2 years ]
    Characterize the safety profile of MRI imaging following direct bladder instillation of a mixture of Gadobutrol and Ferumoxytrol (50mL in sterile water) via urethral catheter by soliciting and recording adverse events while on study.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 18 to 90 years of age
  2. Able to understand and willing to sign a written informed consent document
  3. A papillary tumor identified by cystoscopy that has been scheduled for TURBT OR histologically proven MIBC that is clinically localized and amenable to surgical resection with curative intent.
  4. Performance status of ECOG 0 or 1
  5. Normal renal function as defined as creatinine less than 1.5 x institutional upper limit of normal (ULN) OR creatinine clearance greater than or equal to 50 mL/min/1.73 m2 by Cockroft-Gault formula for subjects with creatinine levels greater than or equal to 1.5 x ULN.

Exclusion Criteria:

  1. Severe hypersensitivity reaction to gadobutrol or ferumoxytol.
  2. Severe claustrophobia that will prevent completion of the MRI study.
  3. Any MRI-non-compatible implanted device, prosthetic or pacemaker.
  4. Known or suspected metastatic disease.
  5. Women with active pregnancy, lactation or plans to conceive
  6. Untreated urinary tract infection
  7. Known urethral stricture disease that would prohibit placement of foley catheter.
  8. Any other conditions considered as unacceptable risk by the treating physician

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04369560


Contacts
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Contact: Dawn McBride, RN 412-623-2764 mcbridedl@upmc.edu

Locations
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United States, Pennsylvania
UPMC Department of Urology Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Joseph Craig, RN    412-623-2764    craigj2@upmc.edu   
Sponsors and Collaborators
Jodi Maranchie
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jodi K Maranchie, MD Associate Professor
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Responsible Party: Jodi Maranchie, Associate Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT04369560    
Other Study ID Numbers: STUDY20020173
First Posted: April 30, 2020    Key Record Dates
Last Update Posted: September 21, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description:
  1. What data will be shared? The investigators will share the accuracy of the MRI staging versus the traditional pathological staging.
  2. Who will have access to the data? The investigators and future researchers who provide the proper MTA, IRB, etc. will have access to the de-identified data.
  3. Where will the data to be shared be located? De-identified data will be kept on the UPMC cloud.
  4. When will the data be shared? The data will be available to share after final analysis and publication of results.
  5. How will researchers locate and access the data? A link to the Cloud folder will be provided.

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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 Jodi Maranchie, University of Pittsburgh:
TURBT
Complete Cystectomy
Additional relevant MeSH terms:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Ferrosoferric Oxide
Hematinics
Parenteral Nutrition Solutions
Pharmaceutical Solutions