Clinical trial NCT05917860: Neoadjuvant ADT with TULSA in the Treatment of Intermediate Risk Prostate Cancer
Official title: Effect of Neoadjuvant Degarelix on MRI-guided Transurethral Ultrasound Ablation (TULSA) in Patients with Intermediate-risk Prostate Cancer: a Pilot Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
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
Lead sponsor: Turku University Hospital
Sponsor class: OTHER_GOV
First posted: 2023-06-26
Enrollment: 15
Sex: MALE
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Procedure: Magnetic resonance imaging-guided transurethral ultrasound ablation of the prostate (TULSA)

Drug: Degarelix
Primary purpose: TREATMENT

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.

Detailed description: Androgen deprivation therapy (ADT) has been shown to reduce prostate and tumor size. In this study, magnetic resonance imaging (MRI) is used to investigate the effect of Degarelix ADT on the properties of prostate tissue that can affect the heating of the tissues in the TULSA procedure. The main goal is to find out if ADT can change the tissue structure in a way that improves the ability of the TULSA procedure to heat tissues and better kill the diseased tissue, reducing the chance of the disease reoccurring. ADT and the TULSA procedure can help patients with more aggressive diseases avoid the adverse effects associated with surgery or radiation therapy. Specific objectives are:

1. To measure the change in prostate and tumor size, tissue structural changes, and the blood flow within the prostate after ADT.
2. To measure the distribution of heating over the prostate after TULSA treatment.
3. To evaluate complications and genitourinary function and quality of life with patient-reported outcome measures.
4. To evaluate local cancer control and longer-term oncological outcomes after combination therapy of neoadjuvant ADT and TULSA treatment.

About 15 subjects will participate. Each will receive Degarelix for three months, followed by whole-prostate gland TULSA treatment, and be followed for five years. Throughout the study, subjects will receive MRI scans and complete questionnaires regarding functional status and quality of life to understand the side effects.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change in prostate volume after neoadjuvant ADT
timeFrame: Baseline and four, eight, and 12 weeks of ADT.
measure: Change in prostate tumor volume after neoadjuvant ADT
timeFrame: Baseline and four, eight, and 12 weeks of ADT.
measure: The frequency and severity of adverse events
timeFrame: Every follow-up visit until the first year of follow-up.
Secondary outcomes:
measure: Change in prostate tumor-capsule contact length after neoadjuvant ADT
timeFrame: Baseline and four, eight, and 12 weeks of ADT.
measure: Change in prostate vascular perfusion after neoadjuvant ADT
timeFrame: Baseline and four, eight, and 12 weeks of ADT.
measure: Change in prostate tumor vascular perfusion after neoadjuvant ADT
timeFrame: Baseline and four, eight, and 12 weeks of ADT.
measure: Change in periprostatic, prostate and tumor tissue structures after neoadjuvant ADT
timeFrame: Baseline and four, eight, and 12 weeks of ADT.
measure: Thermal coverage after whole-prostate gland TULSA
timeFrame: Immediately after the TULSA procedure.
measure: Change in quality of life (QoL) and functional status outcomes after neoadjuvant ADT
timeFrame: Baseline and 12 weeks of ADT.
measure: Change in lower urinary tract symptoms after neoadjuvant ADT
timeFrame: Baseline and 12 weeks of ADT.
measure: Change in erectile function after neoadjuvant ADT
timeFrame: Baseline and 12 weeks of ADT.
measure: Change in quality of life (QoL) and functional status outcomes after neoadjuvant ADT and whole-prostate gland TULSA
timeFrame: Baseline and 12 weeks of ADT, and three, six, 12, 36 and 60 months after the TULSA procedure.
measure: Change in lower urinary tract symptoms after neoadjuvant ADT and whole-prostate gland TULSA
timeFrame: Baseline and 12 weeks of ADT, and three, six, 12, 36 and 60 months after the TULSA procedure.
measure: Change in erectile function after neoadjuvant ADT and whole-prostate gland TULSA
timeFrame: Baseline and 12 weeks of ADT, and three, six, 12, 36 and 60 months after the TULSA procedure.
measure: The frequency and severity of adverse events during extended follow-up
timeFrame: Every follow-up visit until the five years of follow-up.
measure: Salvage therapy-free survival
timeFrame: Every post-TULSA follow-up visit until the five years of follow-up.
measure: Systemic therapy-free survival
timeFrame: Every post-TULSA follow-up visit until the five years of follow-up.
measure: Failure-free survival
timeFrame: Every post-TULSA follow-up visit until the five years of follow-up.
measure: Metastasis-free, prostate cancer-specific, and overall survival
timeFrame: One, three and five years after the TULSA procedure.
measure: Biochemical failure-free survival
timeFrame: One, three, and five years after the TULSA procedure.
measure: Freedom from biopsy-proven clinically-significant prostate cancer
timeFrame: Twelve months after the TULSA procedure
measure: Freedom from any biopsy-proven prostate cancer
timeFrame: Twelve months after the TULSA procedure
Other outcomes:
measure: Change in prostate volume after whole-prostate gland TULSA
timeFrame: Three and twelve months after TULSA procedure
measure: Change in maximum urinary flow rate after neoadjuvant ADT and whole-gland TULSA
timeFrame: Baseline, 12 weeks of ADT, and three, 12, 36 and 60 months after the TULSA procedure
measure: Change in average urinary flow rate after neoadjuvant ADT and whole-gland TULSA
timeFrame: Baseline, 12 weeks of ADT, and three, 12, 36 and 60 months after the TULSA procedure
measure: Change in post-void residual volume after neoadjuvant ADT and whole-gland TULSA
timeFrame: Baseline, 12 weeks of ADT, and three, 12, 36 and 60 months after the TULSA procedure
measure: Change in voided volume after neoadjuvant ADT and whole-gland TULSA
timeFrame: Baseline, 12 weeks of ADT, and three, 12, 36 and 60 months after the TULSA procedure
measure: Freedom from any suspicious lesion on MRI
timeFrame: Three and twelve months after the TULSA procedure
Locations:
city: Turku
country: Finland
facility: Turku University Hospital
state: Southwest Finland
Study officials:
affiliation: Department of Urology, University of Turku and Turku University Hospital, Turku, Finland
name: Mikael HJ Anttinen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: EAU Guidelines 2023, presented at the EAU Annual Congress Milan 2023. ISBN 978-94-92671-16-5.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.