Robot-Assisted Laparoscopic High-Intensity Focused Ultrasound and Radical Cystectomy for Thermal Ablation of Muscle Invasive Cells in Patients With Bladder Tumors
Primary Purpose
Infiltrating Bladder Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma, Transitional Cell Carcinoma
Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Biopsy
High-Intensity Focused Ultrasound Ablation
Laboratory Biomarker Analysis
Radical Cystectomy
Ultrasonography
Sponsored by
About this trial
This is an interventional treatment trial for Infiltrating Bladder Urothelial Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Must meet all inclusion and exclusion criteria
- Presence of a muscle invasive bladder tumor(s) (T2), specific for transitional cell carcinoma on pre-operative histology (i.e. biopsy or transurethral resection of bladder tumor [TURBT]).
- Presence of a single bladder tumor lesion
- Patients are scheduled to undergo RARC at our institution
- Subjects must have given written informed consent to agree to participate
- Previous chemotherapy, and/or biological therapy for cancer are permitted provided that the acoustic properties of the tumor were not affected, but the subject should have recovered from the effects of these or of any prior surgery; chemotherapy can be within 70 days of operation
- Subjects must be free of any clinically significant disease other than cancer that would interfere with the study evaluations
- Pre-operative computed tomography (CT)/magnetic resonance imaging (MRI) abdomen and pelvis within 90 days
- Absolute neutrophil count (ANC) >= 1500 mm^-3
- Platelet count >= 100,000 mm^-3
- Hemoglobin >= 10 g/dl
- Prothrombin time (PT) =< 1.5 times upper limit of laboratory normal (ULN)
- Activated partial thromboplastin time =< 1.5 times ULN
- Total bilirubin < 1.5 times ULN
- Aspartate aminotransferase (AST) =< 3 times ULN
- Alkaline phosphatase < 2 times ULN, unless arising from bone
Exclusion Criteria:
- Subjects deemed unsuitable candidates and not medically optimized for RARC
- Subjects with tumors lying < 1 cm from sensitive structures such as the ureter, prostate or adjacent bowel
- Patients with presence of multiple bladder lesions
- Subjects on concurrent anticoagulant, or immunosuppressive medication
- Patients with pre-operative histologic confirmation of a bladder lesion other than transitional cell carcinoma
- Subjects on anti-cancer medication whether biologic or pharmaceutical
- Women who are pregnant or nursing (pregnancy test to be performed within 24 hours prior to HIFU treatment)
- Subjects assessed by consultant anesthetist as unsuitable for general anesthetic
- Absolute contraindications: venous injury at the level of the femoral veins or proximally; known or suspected thrombosis of the femoral or iliac veins on the proposed side of venous cannulation, ambulatory patient
- Relative contraindications: presence of bleeding disorders; distortion of anatomy due to local injury or deformity; previous long-term venous catheterization; history of vasculitis; previous injection of sclerosis agents; previous radiation therapy
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm A (laparoscopic HIFU, RARC)
Arm B (RARC)
Arm Description
Patients undergo pre-HIFU CEUS, standard of care biopsy of the bladder tumor, laparoscopic HIFU, and post-HIFU CEUS. Patients then undergo standard of care RARC.
Patients undergo standard of care RARC.
Outcomes
Primary Outcome Measures
Complete ablation of the targeted lesion in the bladder wall assessed by histopathologic examination and Live/Dead Viability/Cytotoxicity Assay Kit of the resected specimen (Arm A)
A Clopper-Pearson (exact) 90% confidence interval will be constructed for the probability of a successful HIFU procedure.
CTC enumeration assessed using quantitative real-time polymerase chain reaction
The mean number of CTCs in each patient, as well as the difference between the two arms (possibly after log or square root transformation) will be estimated. Importantly the numbers of CTCs captured in the femoral lines will be compared to the numbers captured in the peripheral lines. Means and 90% confidence intervals will be calculated. Changes in CTC enumeration in a group that undergoes HIFU (Arm A) to a group that does not undergo HIFU (Arm B) will be observed.
Secondary Outcome Measures
Incidence of adverse events evaluated according to National Cancer Institute Criteria for Adverse Events version 4.0 (Arm A)
The complication observed in all patents in each arm will be reported and summarized. For Arm A, focus will be on the complications that might be associated with the HIFU procedure; for Arm B, focus will be on the safety of placed a line in the femoral vein.
Full Information
NCT ID
NCT03238664
First Posted
July 31, 2017
Last Updated
December 28, 2017
Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT03238664
Brief Title
Robot-Assisted Laparoscopic High-Intensity Focused Ultrasound and Radical Cystectomy for Thermal Ablation of Muscle Invasive Cells in Patients With Bladder Tumors
Official Title
Robot-Assisted Laparoscopic HIFU (High-Intensity Focused Ultrasound) of the Bladder Wall for Thermal Ablation of Muscle Invasive Cells of Bladder Tumors: Corroborating With Robot-Assisted Radical Cystectomy
Study Type
Interventional
2. Study Status
Record Verification Date
December 2017
Overall Recruitment Status
Withdrawn
Why Stopped
No funding
Study Start Date
January 22, 2018 (Anticipated)
Primary Completion Date
January 22, 2019 (Anticipated)
Study Completion Date
January 22, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southern California
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
Yes
5. Study Description
Brief Summary
This randomized pilot trial studies how well robot-assisted laparoscopic high-intensity focused ultrasound works compared to robot-assisted radical cystectomy for thermal ablation of muscle invasive cells in patients with bladder tumors. Laparoscopic high-intensity focused ultrasound uses high frequency sound waves to deliver a strong beam to a specific part of the tumor and may lower the number of tumor cells released into the blood stream compared to radical cystectomy.
Detailed Description
PRIMARY OBJECTIVES:
I. To obtain preliminary estimates of the efficacy of laparoscopic high-intensity focused ultrasound (HIFU) for the treatment of localized primary bladder cancer.
II. To estimate the change in the number of expelled circulating tumor cells (CTCs), when comparing HIFU to robot-assisted radical cystectomy (RARC) alone.
SECONDARY OBJECTIVES:
I. To evaluate the safety and toxicity of using laparoscopic HIFU.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients undergo pre-HIFU contrast-enhanced ultrasound (CEUS), standard of care biopsy of the bladder tumor, laparoscopic HIFU, and post-HIFU CEUS. Patients then undergo standard of care RARC.
ARM B: Patients undergo standard of care RARC.
After completion of study, patients are followed up at 2 weeks and 3 months.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infiltrating Bladder Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma, Transitional Cell Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A (laparoscopic HIFU, RARC)
Arm Type
Experimental
Arm Description
Patients undergo pre-HIFU CEUS, standard of care biopsy of the bladder tumor, laparoscopic HIFU, and post-HIFU CEUS. Patients then undergo standard of care RARC.
Arm Title
Arm B (RARC)
Arm Type
Active Comparator
Arm Description
Patients undergo standard of care RARC.
Intervention Type
Procedure
Intervention Name(s)
Biopsy
Other Intervention Name(s)
Bx
Intervention Description
Undergo biopsy of bladder tumor
Intervention Type
Device
Intervention Name(s)
High-Intensity Focused Ultrasound Ablation
Other Intervention Name(s)
HIFU, high-intensity focused ultrasound therapy
Intervention Description
Undergo laparoscopic HIFU
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Procedure
Intervention Name(s)
Radical Cystectomy
Other Intervention Name(s)
Complete Cystectomy
Intervention Description
Undergo RARC
Intervention Type
Device
Intervention Name(s)
Ultrasonography
Other Intervention Name(s)
2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasound, Ultrasound Imaging, Ultrasound Test, Ultrasound, Medical, US
Intervention Description
Undergo CEUS
Primary Outcome Measure Information:
Title
Complete ablation of the targeted lesion in the bladder wall assessed by histopathologic examination and Live/Dead Viability/Cytotoxicity Assay Kit of the resected specimen (Arm A)
Description
A Clopper-Pearson (exact) 90% confidence interval will be constructed for the probability of a successful HIFU procedure.
Time Frame
At the day of surgery
Title
CTC enumeration assessed using quantitative real-time polymerase chain reaction
Description
The mean number of CTCs in each patient, as well as the difference between the two arms (possibly after log or square root transformation) will be estimated. Importantly the numbers of CTCs captured in the femoral lines will be compared to the numbers captured in the peripheral lines. Means and 90% confidence intervals will be calculated. Changes in CTC enumeration in a group that undergoes HIFU (Arm A) to a group that does not undergo HIFU (Arm B) will be observed.
Time Frame
Up to 7 days post-surgery
Secondary Outcome Measure Information:
Title
Incidence of adverse events evaluated according to National Cancer Institute Criteria for Adverse Events version 4.0 (Arm A)
Description
The complication observed in all patents in each arm will be reported and summarized. For Arm A, focus will be on the complications that might be associated with the HIFU procedure; for Arm B, focus will be on the safety of placed a line in the femoral vein.
Time Frame
Up to 3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Must meet all inclusion and exclusion criteria
Presence of a muscle invasive bladder tumor(s) (T2), specific for transitional cell carcinoma on pre-operative histology (i.e. biopsy or transurethral resection of bladder tumor [TURBT]).
Presence of a single bladder tumor lesion
Patients are scheduled to undergo RARC at our institution
Subjects must have given written informed consent to agree to participate
Previous chemotherapy, and/or biological therapy for cancer are permitted provided that the acoustic properties of the tumor were not affected, but the subject should have recovered from the effects of these or of any prior surgery; chemotherapy can be within 70 days of operation
Subjects must be free of any clinically significant disease other than cancer that would interfere with the study evaluations
Pre-operative computed tomography (CT)/magnetic resonance imaging (MRI) abdomen and pelvis within 90 days
Absolute neutrophil count (ANC) >= 1500 mm^-3
Platelet count >= 100,000 mm^-3
Hemoglobin >= 10 g/dl
Prothrombin time (PT) =< 1.5 times upper limit of laboratory normal (ULN)
Activated partial thromboplastin time =< 1.5 times ULN
Total bilirubin < 1.5 times ULN
Aspartate aminotransferase (AST) =< 3 times ULN
Alkaline phosphatase < 2 times ULN, unless arising from bone
Exclusion Criteria:
Subjects deemed unsuitable candidates and not medically optimized for RARC
Subjects with tumors lying < 1 cm from sensitive structures such as the ureter, prostate or adjacent bowel
Patients with presence of multiple bladder lesions
Subjects on concurrent anticoagulant, or immunosuppressive medication
Patients with pre-operative histologic confirmation of a bladder lesion other than transitional cell carcinoma
Subjects on anti-cancer medication whether biologic or pharmaceutical
Women who are pregnant or nursing (pregnancy test to be performed within 24 hours prior to HIFU treatment)
Subjects assessed by consultant anesthetist as unsuitable for general anesthetic
Absolute contraindications: venous injury at the level of the femoral veins or proximally; known or suspected thrombosis of the femoral or iliac veins on the proposed side of venous cannulation, ambulatory patient
Relative contraindications: presence of bleeding disorders; distortion of anatomy due to local injury or deformity; previous long-term venous catheterization; history of vasculitis; previous injection of sclerosis agents; previous radiation therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Inderbir Gill, MD
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Robot-Assisted Laparoscopic High-Intensity Focused Ultrasound and Radical Cystectomy for Thermal Ablation of Muscle Invasive Cells in Patients With Bladder Tumors
We'll reach out to this number within 24 hrs