Virtual Histology of the Bladder Wall for Bladder Cancer Staging

Official title

Virtual Histology of the Bladder Wall for Bladder Cancer Staging; A Novel Intravesical Contrast-Enhanced MRI for Bladder Cancer Staging

Overview

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.

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.

Interventions

• 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).
• 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.

Primary outcome measures

• Accuracy of Magnetic Resonance Imaging assessment of depth of bladder wall penetration to predict pathologic stage determined at tumor resection [Time frame: 4 weeks]

Secondary outcome measures (2)

• Accuracy of Magnetic Resonance Imaging to detect residual/recurrent bladder tumor [Time frame: 4 weeks]
• Rate of Adverse Events [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• 18 to 90 years of age
• Able to understand and willing to sign a written informed consent document
• 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.
• Performance status of ECOG 0 or 1
• 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 Cockcroft-Gault formula for subjects with creatinine levels greater than or equal to 1.5 x ULN.

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 1 center

• UPMC Hillman Cancer Center - Dept of Urology — Pittsburgh

Identifiers

NCT: NCT04369560 · HCC 20-054

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗