Bladder Fiducial Markers and Multiparametric-MRI (Mp-MRI) to Optimize Bladder Chemo-radiotherapy (FMBRT)
Primary Purpose
Bladder Cancer, Urinary Bladder Neoplasm, Urologic Neoplasms
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Fiducial marker placement
Multiparametric MRI (mpMRI)
Sponsored by
About this trial
This is an interventional treatment trial for Bladder Cancer focused on measuring Fiducial marker, Fiducial marker guided technique
Eligibility Criteria
Inclusion Criteria:
- Pathologically (histologically or cytologically) proven diagnosis of primary urothelial carcinoma of the bladder. Subjects with mixed histology are required to have a dominant traditional cell carcinoma (TCC) pattern.
- Clinical stage T2-T4a, Nx, M0 considered appropriate for, and electing to receive, chemoradiation of the bladder
- Planned TURBT as part of the normal course treatment, to take place prior to the initiation of chemo irradiation
- Adequate renal function: Serum creatinine < 2 mg/dL OR calculated creatinine clearance (CrCl) > 30ml/min
- Ability to understand and willingness to sign a written informed consent
Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, during study participation, and for 90 days after study treatment discontinuation
- Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
Exclusion Criteria:
- Subjects with primary TCC of the ureter, urethra, or renal pelvis, without TCC of the bladder, are not allowed
Known distant metastatic disease (e.g. pulmonary or hepatic metastases)
- Subjects with malignant lymphadenopathy in the abdomen or pelvis considered appropriate for radical cystectomy and lymphadenectomy with the goal of complete resection of all malignant disease are allowed
- Patients with bladder abnormalities that preclude safe placement of fiducial markers (i.e. abundant large diverticuli or cellules, active or recurrent urinary infection)
- Planned (or prior history of) definitive bladder irradiation
- Intravesical chemo- or biologic therapy within 6 weeks of first treatment
- Any planned neoadjuvant systemic immunotherapy. Note that prior bacille Calmette-Guerin vaccine (BCG) is not an exclusion
- Clinically significant active infection or uncontrolled medical condition that would preclude participation in study
- Pregnant or nursing women are excluded
- Previous malignancy other than TCC that, in the opinion of the treating investigator, is likely to interfere with protocol treatment
- Individuals with severe renal failure and cannot receive MRI contrast
Sites / Locations
- Cedars-Sinai Medical Center (CSMC)Recruiting
- University of California Los AngelesRecruiting
- Harvard School of Medicine/Massachusetts General Hospital (MGH)Recruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single Arm - Bladder Chemo-Radiotherapy
Arm Description
Fiducial marker placement & cystogram during resection surgery, followed by radiation planning CT scan, mpMRI, chemo-radiation treatment; mpMRI and/or surveillance cystoscopy at 3, 6, and 9 months post-treatment.
Outcomes
Primary Outcome Measures
Bladder volume differential
Change in bladder volumes targeted for high dose radiation (HDR) between the first (Baseline) dose volume histogram (DVH) without the fiducial markers present, compared to the second DVH made after placement of the fiducial markers
Secondary Outcome Measures
Net dose radiation to collateral organs differential
comparison of a DVH (Dose Volume Histogram) made without the fiducial markers present, to the second DVH made with the fiducial markers present. This will be measured by net dose (Gy to area and/or volume) to collateral organs
Positive Predictive Value of Multiparametric-MRI (mp-MRI)
percentage of actual positive sites among those predicted positive by mpMRI
Difference in alignment when markers are incorporated into the planning
Difference in "on-table" patient alignment under the radiotherapy gantry (in millimeters, in X, Y and Z dimensions) when the patient is aligned daily based on conventional methods only (i.e. fiducial markers are not used for alignment), and when the patient is aligned based on the fiducial markers as the reference.
Full Information
NCT ID
NCT04442724
First Posted
June 18, 2020
Last Updated
September 23, 2023
Sponsor
Cedars-Sinai Medical Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT04442724
Brief Title
Bladder Fiducial Markers and Multiparametric-MRI (Mp-MRI) to Optimize Bladder Chemo-radiotherapy
Acronym
FMBRT
Official Title
Bladder Fiducial Markers and Multiparametric-MRI (Mp-MRI) to Optimize Bladder Chemo-radiotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2020 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Cedars-Sinai Medical Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to examine the usefulness of implanting small 24-K gold fiducial markers around a bladder tumor site, so that a Radiation Oncologist can identify the original tumor location at the time of radiation treatment. Other goals of the study include assessing whether a new MRI imaging technology can help with detection of bladder cancer earlier and more accurately when evidence of bladder cancer is not visible by scope.
Detailed Description
This study of fiducial markers in patients with localized muscle-invasive bladder cancer will enroll patients electing bladder preservation with tri-modal therapy.
24-K gold fiducial markers will be endoscopically implanted around the tumor resection area to mark the location of the tumor site, into the bladder wall submucosa space under direct visualization via a coaxial needle. The markers are visible on all imaging modalities, including all available on-table imaging (e.g., portal and cone-beam CT) used for radiotherapy. Reliable fiducial marker placement within the bladder may have the potential to advance bladder-sparing management of localized muscle-invasive bladder cancer.
This study will examine the effectiveness of bladder-preserving multi-modal treatment of muscle-invasive bladder cancer with and without fiducial marker placement to guide radiotherapy targeting and to minimize collateral radiation. In addition, this study intends to verify the accuracy and report on the sensitivity and specificity of mp-MRI imaging to detect the presence and location of bladder cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer, Urinary Bladder Neoplasm, Urologic Neoplasms, Neoplasms, Urinary Bladder Diseases
Keywords
Fiducial marker, Fiducial marker guided technique
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Single Arm - Bladder Chemo-Radiotherapy
Arm Type
Experimental
Arm Description
Fiducial marker placement & cystogram during resection surgery, followed by radiation planning CT scan, mpMRI, chemo-radiation treatment; mpMRI and/or surveillance cystoscopy at 3, 6, and 9 months post-treatment.
Intervention Type
Procedure
Intervention Name(s)
Fiducial marker placement
Intervention Description
placement of 24k gold fiducial markers surrounding the tumor site, at time of primary or re-staging bladder tumor resection
Intervention Type
Diagnostic Test
Intervention Name(s)
Multiparametric MRI (mpMRI)
Intervention Description
In this study, mp-MRI is defined as MRI that includes T1 & T2 weighted sequences, diffusion weighted sequences, and Dynamic contrast enhanced (DCE) MRI sequences.
Primary Outcome Measure Information:
Title
Bladder volume differential
Description
Change in bladder volumes targeted for high dose radiation (HDR) between the first (Baseline) dose volume histogram (DVH) without the fiducial markers present, compared to the second DVH made after placement of the fiducial markers
Time Frame
Baseline, after marker placement (anticipated to occur between study days 0-1)
Secondary Outcome Measure Information:
Title
Net dose radiation to collateral organs differential
Description
comparison of a DVH (Dose Volume Histogram) made without the fiducial markers present, to the second DVH made with the fiducial markers present. This will be measured by net dose (Gy to area and/or volume) to collateral organs
Time Frame
Baseline, after marker placement (anticipated to occur between study days 0-1)
Title
Positive Predictive Value of Multiparametric-MRI (mp-MRI)
Description
percentage of actual positive sites among those predicted positive by mpMRI
Time Frame
at the time of initial TURBT (Day 1), at the initial post-treatment surveillance cystoscopy (3 months post-treatment)
Title
Difference in alignment when markers are incorporated into the planning
Description
Difference in "on-table" patient alignment under the radiotherapy gantry (in millimeters, in X, Y and Z dimensions) when the patient is aligned daily based on conventional methods only (i.e. fiducial markers are not used for alignment), and when the patient is aligned based on the fiducial markers as the reference.
Time Frame
Radiotherapy treatment period (Days 14-28)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pathologically (histologically or cytologically) proven diagnosis of primary urothelial carcinoma of the bladder. Subjects with mixed histology are required to have a dominant traditional cell carcinoma (TCC) pattern.
Clinical stage T2-T4a, Nx, M0 considered appropriate for, and electing to receive, chemoradiation of the bladder
Planned TURBT as part of the normal course treatment, to take place prior to the initiation of chemo irradiation
Adequate renal function: Serum creatinine < 2 mg/dL OR calculated creatinine clearance (CrCl) > 30ml/min
Ability to understand and willingness to sign a written informed consent
Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, during study participation, and for 90 days after study treatment discontinuation
Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
Exclusion Criteria:
Subjects with primary TCC of the ureter, urethra, or renal pelvis, without TCC of the bladder, are not allowed
Known distant metastatic disease (e.g. pulmonary or hepatic metastases)
Subjects with malignant lymphadenopathy in the abdomen or pelvis considered appropriate for radical cystectomy and lymphadenectomy with the goal of complete resection of all malignant disease are allowed
Patients with bladder abnormalities that preclude safe placement of fiducial markers (i.e. abundant large diverticuli or cellules, active or recurrent urinary infection)
Planned (or prior history of) definitive bladder irradiation
Intravesical chemo- or biologic therapy within 6 weeks of first treatment
Any planned neoadjuvant systemic immunotherapy. Note that prior bacille Calmette-Guerin vaccine (BCG) is not an exclusion
Clinically significant active infection or uncontrolled medical condition that would preclude participation in study
Pregnant or nursing women are excluded
Previous malignancy other than TCC that, in the opinion of the treating investigator, is likely to interfere with protocol treatment
Individuals with severe renal failure and cannot receive MRI contrast
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Laura Sarmiento, CCRP
Phone
310-423-4295
Email
laura.sarmiento@cshs.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maurice Garcia, MD
Organizational Affiliation
Cedars-Sinai Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cedars-Sinai Medical Center (CSMC)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Individual Site Status
Recruiting
Facility Name
University of California Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jackie Hernandez, CCRP
Phone
310-267-8991
Email
jhernandez@mednet.ucla.edu
Facility Name
Harvard School of Medicine/Massachusetts General Hospital (MGH)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sarah Stec
Email
SSTEC@mgh.harvard.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Bladder Fiducial Markers and Multiparametric-MRI (Mp-MRI) to Optimize Bladder Chemo-radiotherapy
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