Neoadjuvant ADT with TULSA in the Treatment of Intermediate Risk Prostate Cancer

NCT05917860 | Active Not Recruiting Phase 1

• 1 other identifier: T1338/2023
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Clinical studies have shown that magnetic resonance imaging-guided transurethral ultrasound ablation (TULSA) of the prostate is safe and effective. In the TULSA procedure, prostate tissue is killed by heating with ultrasound. This clinical trial explores if adding drug therapy with Degarelix before TULSA has the potential to improve further the effectiveness of TULSA in the treatment of localized prostate cancer, especially for patients with more aggressive diseases.

Conditions

Localized Prostate Carcinoma; Castration-Naive Prostate Cancer; Intermediate Risk Prostate Cancer; Prostate Cancer

Keywords

MRI-guided transurethral ultrasound ablation; Androgen deprivation therapy; Neoadjuvant androgen deprivation therapy; TULSA; Prostate cancer; Thermal ablation; Therapeutic ultrasound; Ablation therapy

Outcome Measures

Primary Outcomes (3)

• Change in prostate volume after neoadjuvant ADT

  The prostate volume change will be determined by comparing the prostate volume measured on T2-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.

  Baseline and four, eight, and 12 weeks of ADT.

• Change in prostate tumor volume after neoadjuvant ADT

  The prostate tumor volume change will be determined by comparing the prostate tumor volume measured on T2-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.

  Baseline and four, eight, and 12 weeks of ADT.

• The frequency and severity of adverse events

  The frequency and severity of adverse events after neoadjuvant Degarelix and TULSA treatment will be determined by using the CTCAE v6.0 classification. Adverse events attributed to TULSA will also be graded using the Clavien Dindo classification for surgical complications.

  Every follow-up visit until the first year of follow-up.

Secondary Outcomes (19)

• Change in prostate tumor-capsule contact length after neoadjuvant ADT

  Baseline and four, eight, and 12 weeks of ADT.

• Change in prostate vascular perfusion after neoadjuvant ADT

  Baseline and four, eight, and 12 weeks of ADT.

• Change in prostate tumor vascular perfusion after neoadjuvant ADT

  Baseline and four, eight, and 12 weeks of ADT.

• Change in periprostatic, prostate and tumor tissue structures after neoadjuvant ADT

  Baseline and four, eight, and 12 weeks of ADT.

• Thermal coverage after whole-prostate gland TULSA

  Immediately after the TULSA procedure.

Other Outcomes (6)

• Change in prostate volume after whole-prostate gland TULSA

  Three and twelve months after TULSA procedure

• Change in maximum urinary flow rate after neoadjuvant ADT and whole-gland TULSA

  Baseline, 12 weeks of ADT, and three, 12, 36 and 60 months after the TULSA procedure

• Change in average urinary flow rate after neoadjuvant ADT and whole-gland TULSA

  Baseline, 12 weeks of ADT, and three, 12, 36 and 60 months after the TULSA procedure

Study Arms (1)

3-month neoadjuvant Degarelix followed by whole-gland MRI-guided transurethral ultrasound ablation

EXPERIMENTAL

After three months of neoadjuvant ADT with Degarelix, the subject will undergo whole-prostate gland MRI-guided transurethral ultrasound ablation (TULSA) (TULSA-PRO, Profound Medical Inc., Toronto, Canada) treatment.

Drug: Degarelix; Device: MRI-guided transurethral ultrasound ablation (TULSA)

Interventions

Degarelix DRUG

Degarelix is injected subcutaneously into the fatty tissue of the abdomen. A typical protocol consists of a starting dose of 240 mg with a maintenance dose of 80 mg administered every 28 days. In this study, one starting dose and two maintenance doses of Degarelix will be administered between baseline and TULSA treatment in accordance with the terms of Degarelix marketing authorizations.

Also known as: Firmagon

3-month neoadjuvant Degarelix followed by whole-gland MRI-guided transurethral ultrasound ablation

MRI-guided transurethral ultrasound ablation (TULSA) DEVICE

MRI-guided transurethral ultrasound ablation (TULSA) (TULSA-PRO, Profound Medical Inc., Toronto, Canada) will be used to deliver whole-prostate gland treatment in accordance with the terms of TULSA marketing authorizations. The treating physicians will contour the entire prostate gland for a whole gland ablation.

Also known as: TULSA-PRO

3-month neoadjuvant Degarelix followed by whole-gland MRI-guided transurethral ultrasound ablation

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male age ≥ 40 years and candidate for radical prostate cancer treatment
• Estimated life expectancy \> 8 years
• At least one MRI-visible and biopsy-concordant tumor defined as Prostate Imaging-Reporting and Data System v2 (PI-RADS v2.1) ≥ 3
• Biopsy-confirmed, intermediate-risk localized prostate cancer:
• Clinical or radiological tumor stage ≤ T2c, N0, M0
• ISUP GG 2 or 3
• Biopsy obtained ≥ 6 weeks and ≤ 12 months before treatment
• PSA ≤ 20 ng/ml
• No prior definitive treatment of prostate cancer
• Eligible for MRI
• Eligible for general anesthesia (American Society of Anesthesiologists Class III or less)
• Patients taking 5-alpha reductase inhibitors (5-ARIs) are eligible if use is discontinued three months before and throughout the study period.
• Informed consent: The patient must speak Finnish, English, or Swedish and must be able to understand the meaning of the study. The patient must be willing and able to sign the appropriate Ethics Committee (EC) approved informed consent documents in the presence of the designated staff.

You may not qualify if:

• Prior prostate cancer treatment with chemotherapy or hormonal therapy, including chemical or surgical castration, antiandrogen therapy, or androgen-receptor signaling inhibitors.
• Relative or absolute contraindication to Degarelix
• Severe, active cardiovascular comorbidity including unstable angina pectoris, congestive heart failure, deep vein thrombosis, pulmonary embolism, or myocardial infarction within the last six months.
• Inability to undergo MRI due to claustrophobia or contraindications (cardiac pacemaker, intracranial clips, etc.)
• Severe kidney failure as determined by estimated glomerular filtration rate (eGFR) less than 30 ml/min per 1.73 m2
• Prostate calcifications obstructing the planned ultrasound beam path in the line of sight of the MRI visible tumor
• Prostate cysts at the prostate capsule within the planned ultrasound beam path in the line of sight of the MRI visible tumor
• Evidence of extraprostatic disease based on imaging (MRI, bone scintigraphy, single-photon emission tomography, computed tomography, prostate-specific membrane antigen-positron emission tomography \[PSMA-PET\]) or histopathology
• History of chronic inflammatory conditions (e.g., inflammatory bowel disease) affecting the rectum (also includes rectal fistula and anal/rectal stenosis)
• Hip replacement surgery or other metal in the pelvic area
• Known allergy or contraindication to gadolinium or gastro-intestinal anti-spasmodic drug glucagon
• Concomitant treatment with medications contraindicated to Glucagen used as antispasmolytic agent during TULSA treatment (e.g., Feochromocytoma)
• Any other conditions that might compromise patient safety, based on the clinical judgment of the responsible urologist
• Another primary malignancy unless disease-free survival is \> 8 years

Sponsors & Collaborators

• Turku University Hospital: lead

Study Sites (1)

Turku University Hospital

Turku, Southwest Finland, 20521, Finland

Location

Related Publications (21)

• Anttinen M, Blanco Sequeiros R, Bostrom PJ, Taimen P. Evolving imaging methods of prostate cancer and the emergence of magnetic resonance imaging guided ablation techniques. Front Oncol. 2022 Nov 17;12:1043688. doi: 10.3389/fonc.2022.1043688. eCollection 2022.

  PMID: 36465377 BACKGROUND

• Valerio M, Cerantola Y, Eggener SE, Lepor H, Polascik TJ, Villers A, Emberton M. New and Established Technology in Focal Ablation of the Prostate: A Systematic Review. Eur Urol. 2017 Jan;71(1):17-34. doi: 10.1016/j.eururo.2016.08.044. Epub 2016 Aug 29.

  PMID: 27595377 BACKGROUND

• Klotz L, Pavlovich CP, Chin J, Hatiboglu G, Koch M, Penson D, Raman S, Oto A, Futterer J, Serrallach M, Relle J, Lotan Y, Heidenreich A, Bonekamp D, Haider M, Tirkes T, Arora S, Macura KJ, Costa DN, Persigehl T, Pantuck AJ, Bomers J, Burtnyk M, Staruch R, Eggener S. Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer. J Urol. 2021 Mar;205(3):769-779. doi: 10.1097/JU.0000000000001362. Epub 2020 Oct 6.

  PMID: 33021440 BACKGROUND

• EAU Guidelines 2023, presented at the EAU Annual Congress Milan 2023. ISBN 978-94-92671-16-5.

  BACKGROUND

• Denham JW, Steigler A, Lamb DS, Joseph D, Turner S, Matthews J, Atkinson C, North J, Christie D, Spry NA, Tai KH, Wynne C, D'Este C. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol. 2011 May;12(5):451-9. doi: 10.1016/S1470-2045(11)70063-8.

  PMID: 21440505 BACKGROUND

• Hu J, Xu H, Zhu W, Wu F, Wang J, Ding Q, Jiang H. Neo-adjuvant hormone therapy for non-metastatic prostate cancer: a systematic review and meta-analysis of 5,194 patients. World J Surg Oncol. 2015 Feb 22;13:73. doi: 10.1186/s12957-015-0503-z.

  PMID: 25884478 BACKGROUND

• Nishiyama T. Serum testosterone levels after medical or surgical androgen deprivation: a comprehensive review of the literature. Urol Oncol. 2014 Jan;32(1):38.e17-28. doi: 10.1016/j.urolonc.2013.03.007. Epub 2013 Jun 13.

  PMID: 23769268 BACKGROUND

• Christie DRH, Mitina N, Sharpley CF. A prospective study of the effect of testosterone escape on preradiotherapy prostate-specific antigen kinetics in prostate cancer patients undergoing neoadjuvant androgen deprivation therapy. Curr Urol. 2021 Mar;15(1):63-67. doi: 10.1097/CU9.0000000000000008. Epub 2021 Mar 29.

  PMID: 34084124 BACKGROUND

• Klotz LH, Goldenberg SL, Jewett MA, Fradet Y, Nam R, Barkin J, Chin J, Chatterjee S; Canadian Uro-Oncology Group. Long-term followup of a randomized trial of 0 versus 3 months of neoadjuvant androgen ablation before radical prostatectomy. J Urol. 2003 Sep;170(3):791-4. doi: 10.1097/01.ju.0000081404.98273.fd.

  PMID: 12913699 BACKGROUND

• Kumar S, Shelley M, Harrison C, Coles B, Wilt TJ, Mason MD. Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. Cochrane Database Syst Rev. 2006 Oct 18;2006(4):CD006019. doi: 10.1002/14651858.CD006019.pub2.

  PMID: 17054269 BACKGROUND

• Sumitomo M, Hayashi M, Watanabe T, Tsugawa M, Noma H, Yamaguchi A, Nagakura K, Hayakawa M, Uchida T. Efficacy of short-term androgen deprivation with high-intensity focused ultrasound in the treatment of prostate cancer in Japan. Urology. 2008 Dec;72(6):1335-40. doi: 10.1016/j.urology.2007.12.041. Epub 2008 Mar 20.

  PMID: 18355899 BACKGROUND

• Aoyagi, Teiichiro, and Isao Kuroda. Enhancement of HIFU Effect by Simultaneous Short Course Degarelix for Early Stage Prostate Cancer: A Pilot Study. Open Journal of Urology 6.03 (2016): 49-54.

  BACKGROUND

• Crawford ED, Shore ND, Moul JW, Tombal B, Schroder FH, Miller K, Boccon-Gibod L, Malmberg A, Olesen TK, Persson BE, Klotz L. Long-term tolerability and efficacy of degarelix: 5-year results from a phase III extension trial with a 1-arm crossover from leuprolide to degarelix. Urology. 2014 May;83(5):1122-8. doi: 10.1016/j.urology.2014.01.013. Epub 2014 Mar 22.

  PMID: 24661333 BACKGROUND

• Anttinen M, Makela P, Viitala A, Nurminen P, Suomi V, Sainio T, Saunavaara J, Taimen P, Sequeiros RB, Bostrom PJ. Salvage Magnetic Resonance Imaging-guided Transurethral Ultrasound Ablation for Localized Radiorecurrent Prostate Cancer: 12-Month Functional and Oncological Results. Eur Urol Open Sci. 2020 Nov 25;22:79-87. doi: 10.1016/j.euros.2020.10.007. eCollection 2020 Dec.

  PMID: 34337481 BACKGROUND

• Anttinen M, Makela P, Nurminen P, Yli-Pietila E, Suomi V, Sainio T, Saunavaara J, Taimen P, Blanco Sequeiros R, Bostrom PJ. Palliative MRI-guided transurethral ultrasound ablation for symptomatic locally advanced prostate cancer. Scand J Urol. 2020 Dec;54(6):481-486. doi: 10.1080/21681805.2020.1814857. Epub 2020 Sep 8.

  PMID: 32897169 BACKGROUND

• Dora C, Clarke GM, Frey G, Sella D. Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer: A Systematic Review. J Endourol. 2022 Jun;36(6):841-854. doi: 10.1089/end.2021.0866. Epub 2022 Mar 7.

  PMID: 35029127 BACKGROUND

• Pooli A, Johnson DC, Shirk J, Markovic D, Sadun TY, Sisk AE Jr, Mohammadian Bajgiran A, Afshari Mirak S, Felker ER, Hughes AK, Raman SS, Reiter RE. Predicting Pathological Tumor Size in Prostate Cancer Based on Multiparametric Prostate Magnetic Resonance Imaging and Preoperative Findings. J Urol. 2021 Feb;205(2):444-451. doi: 10.1097/JU.0000000000001389. Epub 2020 Oct 7.

  PMID: 33026934 BACKGROUND

• Bjoreland U, Nyholm T, Jonsson J, Skorpil M, Blomqvist L, Strandberg S, Riklund K, Beckman L, Thellenberg-Karlsson C. Impact of neoadjuvant androgen deprivation therapy on magnetic resonance imaging features in prostate cancer before radiotherapy. Phys Imaging Radiat Oncol. 2021 Feb 24;17:117-123. doi: 10.1016/j.phro.2021.01.004. eCollection 2021 Jan.

  PMID: 33898790 BACKGROUND

• Washino S, Hirai M, Saito K, Kobayashi Y, Arai Y, Miyagawa T. Impact of Androgen Deprivation Therapy on Volume Reduction and Lower Urinary Tract Symptoms in Patients with Prostate Cancer. Low Urin Tract Symptoms. 2018 Jan;10(1):57-63. doi: 10.1111/luts.12142. Epub 2016 Dec 12.

  PMID: 27943566 BACKGROUND

• Hotker AM, Mazaheri Y, Zheng J, Moskowitz CS, Berkowitz J, Lantos JE, Pei X, Zelefsky MJ, Hricak H, Akin O. Prostate Cancer: assessing the effects of androgen-deprivation therapy using quantitative diffusion-weighted and dynamic contrast-enhanced MRI. Eur Radiol. 2015 Sep;25(9):2665-72. doi: 10.1007/s00330-015-3688-1. Epub 2015 Mar 29.

  PMID: 25820537 BACKGROUND

• Marra G, Dell'oglio P, Baghdadi M, Cathelineau X, Sanchez-Salas R; EvaluatioN of HIFU Hemiablation and short-term AndrogeN deprivation therapy Combination to Enhance prostate cancer control (ENHANCE) Study. Multimodal treatment in focal therapy for localized prostate cancer using concomitant short-term androgen deprivation therapy: the ENHANCE prospective pilot study. Minerva Urol Nefrol. 2019 Oct;71(5):544-548. doi: 10.23736/S0393-2249.19.03599-9. Epub 2019 Sep 6.

  PMID: 31508924 BACKGROUND

Related Links

• Turku HIFU research centre

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide

Condition Hierarchy (Ancestors)

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

Study Officials

• Mikael HJ Anttinen, MD, PhD

  Department of Urology, University of Turku and Turku University Hospital, Turku, Finland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Procedure: Magnetic resonance imaging-guided transurethral ultrasound ablation of the prostate (TULSA) Drug: Degarelix

Study Record Dates

• First Submitted: May 2, 2023
• First Posted: June 26, 2023
• Study Start: July 18, 2023
• Primary Completion: January 31, 2026
• Study Completion (Estimated): January 31, 2030
• Last Updated: February 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)