Pilot Study to Investigate Magnetic Resonance (MR) Image Guided Focal Therapy in Prostate Cancer

• ClinicalTrials.gov Identifier: NCT04808427
• Recruitment Status: Recruiting
• First Posted: March 22, 2021
• Last Update Posted: April 9, 2024
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Study Description

Brief Summary:

Background:

The ability to treat early prostate cancer is still limited. Thermal ablation methods are being tested for focal prostate cancer therapy. Researchers want to improve on these methods.

Objective:

To understand if Transurethral UltraSound Ablation (TULSA) in combination with MRI guidance is useful to treat localized prostate cancer.

Eligibility:

English-speaking adults ages 18 and older with localized prostate cancer that can be seen on MRI and can be treated by thermal ablation.

Design:

Participants will be screened with the following:

• Medical history
• Physical exam
• Digital rectal exam
• Blood and urine tests
• Electrocardiogram
• Tumor biopsy
• Questionnaire to assess urinary tract symptoms
• MRI of the pelvis. The MRI scanner is a long, narrow tube. Participants will lie on a bed that moves in and out of the scanner.

Participants may also be screened with the following:

• Echocardiogram
• Chest x-ray
• Bone scan
• Urodynamic studies to see how well the bladder, sphincters, and urethra hold and release urine
• MRI of the brain
• Transrectal ultrasound
• Computer tomography (CT) scan of the chest, abdomen, and pelvis. A CT scan is a series of x-ray images taken of parts of the body.

Some screening tests will be repeated during the study.

Participants will have the TULSA procedure. They will have an MRI for guidance. A small ultrasound applicator will be placed into their urethra. It uses heat to destroy the cancer areas in the prostate. It is controlled by a robotic arm. A cooling catheter will be placed into their rectum.

Participants will use a urethral catheter for 1-7 days.

Participants will have follow-up visits at 3, 6, 12, 18, 24, and 36 months.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Device: TULSA-PRO	Not Applicable

Detailed Description:

Background:

Prostate cancer is relatively slow growing, with doubling times for local tumors estimated at 2 to 4 years.

Some prostate cancers prove to be small, low grade, and noninvasive and they appear to pose little risk to the life or health of the host. Recent patient series suggest that 20% to 30% of men undergoing radical prostatectomy have pathologic features in the radical prostatectomy specimen consistent with an insignificant or "indolent" cancer which poses little threat to life or health.

We propose that participants with low volume and low grade disease can be best served with focal ablation of the visible prostate cancer without the side effects of urinary incontinence and erectile dysfunction associated with radiation therapy or radical surgery.

Focal Therapy for prostate cancer has gained popularity however prior studies demonstrate a failure rate as high as 50% with a laser.

Objective:

To determine the feasibility of magnetic resonance image (MRI)-guided ultrasound-induced thermal therapy of biopsy-confirmed and MRI visible, prostate tumor(s) using the TULSA Thermal Therapy System (Profound Medical)

Eligibility:

Subjects with prostate cancer, amenable for ultrasound ablation

Organ confined clinical T1c or clinical T2a prostate cancer, visible on MRI, and confirmed by prostate biopsy

Adequate organ and marrow function

Prostate-specific antigen (PSA) < 20 ng/ml

Age >=18 years

Design:

Study testing feasibility and tolerability of ultrasound ablation of focal prostate cancer.

It is anticipated that 15 participants will be accrued for this study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Magnetic Resonance Image (MRI) Guided High Energy Ultrasound for Focal Prostate Cancer Ablation
• Actual Study Start Date: November 20, 2023
• Estimated Primary Completion Date: May 1, 2027
• Estimated Study Completion Date: September 1, 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1/Arm 1; Ultrasound ablation of focal prostate cancer	Device: TULSA-PRO; Transurethral MR-Thermometry Guided Ultrasound Ablation of the Prostate

Outcome Measures

Primary Outcome Measures :

1. feasibility and tolerability [ Time Frame: 3, 6, 12, 18, 24, and 36 months ]
   To determine the feasibility of magnetic resonance image (MRI)-guided ultrasound-induced thermal therapy of biopsy-confirmed and MRI visible, prostate tumor(s) using the TULSA Thermal Therapy System (Profound Medical)

Secondary Outcome Measures :

1. safety and tolerability [ Time Frame: 3, 6, 12, 18, 24, and 36 months ]
   Address short- and long-term complication rates of study treatment by tabulating adverse events by grade according to CTCAE, and analyzing and reporting descriptively
2. changes in imaging and biopsy characteristics [ Time Frame: 3, 6, 12, 18, 24, and 36 months ]
   Determine if focal ablation of MRI visible, biopsy-confirmed prostate cancer using the TULSA Thermal Therapy System (Profound Medical) platform can successfully ablate targeted prostate cancer lesions in >50% of participants
3. effect of thermal ablation on short- and long-term complication rates [ Time Frame: 3, 6, 12, 18, 24, and 36 months ]
   Observe thermal damage on post-contrast MRI which extends into areas of the Rectum or Urethra; assess frequency of not completing the procedure
4. thermal damage [ Time Frame: 3, 6, 12, 18, 24, and 36 months ]
   Observe thermal damage on post-contrast MRI which extends into areas of the Rectum or Urethra; assess frequency of not completing the procedure
5. outcome of TULSA ablation [ Time Frame: 3, 6, 12, 18, 24, and 36 months ]
   Use descriptive statistical analysis to examine serial PSA, PSA density, changes in imaging and biopsy, International Prostate Symptom Score (IPSS), and Sexual Health Inventory for Men (SHIM)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

• INCLUSION CRITERIA:

Subjects must have prostate cancer, amenable for ultrasound ablation defined as following:

• diagnosed by prostate biopsies consist of transrectal ultrasound-guided standard 12 core biopsy and biopsies of one or two MRI target lesions;
• Gleason Score <= 7;
• <= 4 cores positive in a standard 12 core biopsy and <= 4 cores positive on MRI target lesions biopsy where 2 cores are taken from each of the one or two MRI target lesions;
• histologically positive standard biopsy cores must be from the same location in the prostate as an MRI target lesion(s) and reviewed by NCI urologic pathologist. (Left / Right, Base, Mid-Gland, Apex).
• organ confined clinical T1c or clinical T2a prostate cancer that is visualized on MRI imaging. Note: Participants after prostate cancer treatment with local recurrence or residual tumor which is visible on MRI are eligible.
• PSA < 20 ng/ml.
• Adults (>= 18 years of age)
• Participants must have adequate organ and marrow function as defined below:

Platelets >= 50,000/mcL

Hemoglobin >= 8 g/dL

ALT or AST <= 5 x ULN

Measured or calculated creatinine clearance (CrCl) (eGFR may also be used in place of CrCl)* >= 30 mL/min/1.73 m^2

ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.

*Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard.

- Subjects must be able to understand and willing to sign a written informed consent document.

EXCLUSION CRITERIA:

• The presence of 3 or more MRI visible lesions positive for prostate cancer on biopsy
• Targeted lesion ablation length from apex to base of >5 cm or lesion extending >3 cm from the urethra.
• Target ablative volume of greater than 100 ml.
• Presence of calcifications that would impede ultrasound transmission between the urethra and ablative target.
• The participant is unable to tolerate MRI (foreign body, i.e., pacemaker or other implanted device; claustrophobia; inability to tolerate rectal coil; etc.)
• The participant with the inability to follow up
• Acute urinary tract infection
• Lower urinary tract symptoms defined by an IPSS > 20
• Participants with uncontrolled coagulopathies (including liver dysfunction, or untreated hereditary coagulopathies which have a standard of care treatment) per surgeon discretion based on bleeding risk.
• Other serious illnesses according to the PI: involving the cardiac, respiratory, CNS, renal, or hepatic organ systems, which would preclude study completion or impede the determination of causality of any complications experienced during the conduct of this study.

Contacts and Locations

Contacts

Contact: Jill M Harper, Ph.D.; (240) 858-7373; jill.harper@nih.gov

Contact: Peter A Pinto, M.D.; (240) 858-3700; pp173u@nih.gov

Locations

United States, Maryland

National Institutes of Health Clinical Center; Recruiting

Bethesda, Maryland, United States, 20892

Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office 888-624-1937

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Peter A Pinto, M.D.; National Cancer Institute (NCI)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page 

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT04808427
• Other Study ID Numbers: 210017; 21-C-0017
• First Posted: March 22, 2021
• Last Update Posted: April 9, 2024
• Last Verified: April 5, 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: .All IPD recorded in the medical record will be shared with intramural investigators upon request
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):

TULSA; Thermal Therapy System; PSA; Gleason Score

Additional relevant MeSH terms:

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