AzTrials
AzTrials

Prostate CancerPhase 3ESTABLISHNCT05232578

Early Salvage Therapy for Patients With Advanced Features for Biochemical Relapse After Radical Prostatectomy for Localized Prostate Carcinoma In Correlation With Supposed Molecular-genetic Parameters of Higher Aggressiveness

A Phase 3 study testing Early salvage radiotherapy (eSRT) and Delayed Salvage radiotherapy (dSRT) in people with Prostate Cancer, run by General University Hospital, Prague.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

The primary objective of the trial is to compare the impact and safety of delayed salvage therapy (dSRT, i.e., SRT initiated at PSA values of 0.4-0.5 ng/ml) to those of early salvage therapy (eSRT, i.e., at PSA levels of 0.2 ng/ml) in patients with biochemical relapse after radical prostatectomy. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Early salvage radiotherapy (eSRT) and Delayed Salvage radiotherapy (dSRT)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
380 participants
Where
No sites listed yet
Study dates
Sep 2022to Dec 2032
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • > 18 years of age
  • Pathologically confirmed invasive prostate carcinoma with minimal 1 risk factor (RF) after radical prostatectomy (RP)
  • Patient refuses the adjuvant therapy after normalization of urinary function within 6 month after RP
  • Signed informed consent to participate in the study and (where necessary) consent to participate in the translational part of the research (not a requirement)
  • ECOG 0 - 1
  • pT2 and minimal 1 risk factor (RF):
Show all 14Show fewer
  • R1 (PSM), and/or
  • Gleason score (4+3=7) 8-10 and/or ISUP grade group 3-5
  • pT3a /pT3b with or without one RF
  • No evidence of suspicious pelvic lymph nodes by initial diagnostic: cN0 and/or pN0
  • No evidence of suspicious distant metastases by initial diagnostic: M0
  • Patient with decline of PSA level to undetectable PSA levels (< 0,1 ng/ml) or around 0,2ng/ml and with another decreasing trends so that the PSA level decline within 12-24 weeks after RP to undetectable levels (< 0,1 ng/ml) and with renewed increase of PSA >0,2 ng/ml (BCR= biochemical relapse) without any clinical relapse on PSMA PET/CT
  • No hormonal therapy prior and /or after the radical prostatectomy
  • Patient suitable and fit for subsequent radiotherapy with high likelihood of good compliance to the follow-up

Who cannot join

  • Life expectancy (based on Charlson comorbidity index) < 10 years
  • Patient not fit for the therapy
  • History of other cancer (other than a radically removed non-melanoma skin carcinoma)
  • Previous pelvic irradiation
  • Active immunosuppressive medication
  • History of hormone therapy prior to randomization
  • cN1 and/or pN1 and M1
  • PSA-persistence after RP (PSA 12-weeks after RP > 0.1 ng/ml or no decreasing trend described in Inclusion criteria)

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Sona Argalacsova, MD, PhD contact

+420224962219

sona.argalacsova@vfn.cz

Otakar Capoun, MD, PhD contact

+420224962219

otakar.capoun@vfn.cz

About this study

The primary objective of the trial is to compare the impact and safety of delayed salvage therapy (dSRT, i.e., SRT initiated at PSA values of 0.4-0.5 ng/ml) to those of early salvage therapy (eSRT, i.e., at PSA levels of 0.2 ng/ml) in patients with biochemical relapse after radical prostatectomy.

The secondary objective of the trial is to perform analysis of the subgroups of patients to determine which patients are most likely to benefit from dSRT

Exploratory objective of the trial is to determine whether selected molecular genetic parameters (172 candidate genes and molecular alterations) and known clinical parameters can be used to identify potential predictors of worse prognosis in patients with known risk factors for relapse after radical prostatectomy, thereby augmenting and refining patient stratification, optimizing their therapy, and clarifying the proper timing of multimodal therapy

Conditions
Prostate Cancer
Being tested
Early salvage radiotherapy (eSRT), Delayed Salvage radiotherapy (dSRT)
Keywords
prostate carcinoma, salvage therapy, biochemical relapse
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Early salvage radiotherapy (eSRT)Radiation

    eSRT administered immediately after the confirmation of the biochemical relapse (PSA ≈ 0.2ng/ml).

    66-70Gy will be delivered to the bed of prostate. Radiotherapy will be optionally accompanied by androgen deprivation therapy.

  • Delayed Salvage radiotherapy (dSRT)Radiation

    dSRT administered if PSA levels increase to ≥ 0.4 ng/ml.

    66-70Gy will be delivered to the bed of prostate. Radiotherapy will be optionally accompanied by androgen deprivation therapy.

Study groups in NCT05232578
Study groupRoleWhat they receive
Arm A- early salvage radiotherapy (eSRT)ExperimentalEarly salvage radiotherapy (eSRT) will be administered immediately after the confirmation of the biochemical relapse (prostate-specific antigen PSA level increase to ≈ 0,2 ng/ml) after radical prostatectomy with defined risk factors and no clinical recurrence signs on prostate specific membrane antigen positron emission tomography and computed tomography (PSMA PET/CT).
Receives: Radiation: Early salvage radiotherapy (eSRT)
Arm B- delayed salvage radiotherapy (dSRT)ExperimentalThe patient is by the biochemical relapse analysis (PSA level 0,2 ng/ml) referred for further follow-up of PSA values. dSRT is initiated, if PSA further increase to values of ≥ 0.4 ng/ml is confirmed and the presence of a potential clinical relapse is excluded with repeated PSMA-PET-CT in line with standard procedures
Receives: Radiation: Delayed Salvage radiotherapy (dSRT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free survival (EFS)

    Defined as a time to re-documented biochemical relapse after salvage therapy (bRFS), demonstration of clinical relapse (i.e.,local relapse /lRFS/, locoregional relapse /lrRFS/, distant relapse /MFS/) and/or death from any cause.

    Measured: Analysed 3 years after randomisation of the last patient.

Secondary outcomes (4)

  1. Carcinoma-specific survival (CSS)

    Measured: Analysed 5/10 years after randomization of the last patient.

  2. Overall survival (5y- and 10y- OS)

    Measured: Analysed 5/10 years after randomization of the last patient.

  3. Incidence of treatment-related acute and late toxicity

    Comparison of the incidence of treatment-related acute and late toxicity between patients after early/ delayed salvage therapy.

    Acute and late toxicity will be assessed and graded using Common Terminology Criteria for Adverse Events (CTCAE).

    Measured: Analysed 5 years after randomization of the last patient.

  4. Health-related quality of life (QoL) assessment.

    The analysis of the QoL of both study ARMs will be made based on EORTC validated questionnaires (QLQ-C30 and QLQ-PR25).

    QLQ-C30 was developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. The EORTC QLQ-PR25 is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 25 items specifically related to prostate cancer.

    Measured: Analysed 5 years after randomization of the last patient.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Feb 2022
  2. Study startSep 2022 (estimated)
  3. Primary completionDec 2032 (estimated)
  4. Study completionDec 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
A "balanced design" is used for the 1:1 randomization into two arms A and B:
Masking
None (open label)
Enrolment
380 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05232578
Sponsor's protocol ID
ESTABLISH 2021 Trial v03.2021
Acronym
ESTABLISH
Status last verified
Aug 2022
First submitted
24 Nov 2021
Last updated
3 Aug 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kneebone A, Fraser-Browne C, Duchesne GM, Fisher R, Frydenberg M, Herschtal A, Williams SG, Brown C, Delprado W, Haworth A, Joseph DJ, Martin JM, Matthews JHL, Millar JL, Sidhom M, Spry N, Tang CI, Turner S, Wiltshire KL, Woo HH, Davis ID, Lim TS, Pearse M. Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): a randomised, controlled, phase 3, non-inferiority trial. Lancet Oncol. 2020 Oct;21(10):1331-1340. doi: 10.1016/S1470-2045(20)30456-3.

    PubMed 33002437

  • Tao R, Dai J, Bai Y, Yang J, Sun G, Zhang X, Zhao J, Zeng H, Shen P. The prognosis benefits of adjuvant versus salvage radiotherapy for patients after radical prostatectomy with adverse pathological features: a systematic review and meta-analysis. Radiat Oncol. 2019 Nov 9;14(1):197. doi: 10.1186/s13014-019-1384-z.

    PubMed 31706339

  • Wiegel T, Bartkowiak D, Bottke D, Bronner C, Steiner U, Siegmann A, Golz R, Storkel S, Willich N, Semjonow A, Stockle M, Rube C, Rebmann U, Kalble T, Feldmann HJ, Wirth M, Hofmann R, Engenhart-Cabillic R, Hinke A, Hinkelbein W, Miller K. Adjuvant radiotherapy versus wait-and-see after radical prostatectomy: 10-year follow-up of the ARO 96-02/AUO AP 09/95 trial. Eur Urol. 2014 Aug;66(2):243-50. doi: 10.1016/j.eururo.2014.03.011. Epub 2014 Mar 21.

    PubMed 24680359

  • Bhindi B, Lokeshwar SD, Klaassen Z, Klotz L, Wallis CJD. Systematic review and meta-analysis of trials evaluating the role of adjuvant radiation after radical prostatectomy for prostate cancer: Implications for early salvage. Can Urol Assoc J. 2020 Oct;14(10):330-336. doi: 10.5489/cuaj.6440.

    PubMed 32432529

  • Bolla M, van Poppel H, Tombal B, Vekemans K, Da Pozzo L, de Reijke TM, Verbaeys A, Bosset JF, van Velthoven R, Colombel M, van de Beek C, Verhagen P, van den Bergh A, Sternberg C, Gasser T, van Tienhoven G, Scalliet P, Haustermans K, Collette L; European Organisation for Research and Treatment of Cancer, Radiation Oncology and Genito-Urinary Groups. Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911). Lancet. 2012 Dec 8;380(9858):2018-27. doi: 10.1016/S0140-6736(12)61253-7. Epub 2012 Oct 19.

    PubMed 23084481

  • Hackman G, Taari K, Tammela TL, Matikainen M, Kouri M, Joensuu T, Luukkaala T, Salonen A, Isotalo T, Petas A, Hendolin N, Bostrom PJ, Aaltomaa S, Lehtoranta K, Hellstrom P, Riikonen J, Korpela M, Minn H, Kellokumpu-Lehtinen PL, Pukkala E, Hemminki A; FinnProstate Group. Randomised Trial of Adjuvant Radiotherapy Following Radical Prostatectomy Versus Radical Prostatectomy Alone in Prostate Cancer Patients with Positive Margins or Extracapsular Extension. Eur Urol. 2019 Nov;76(5):586-595. doi: 10.1016/j.eururo.2019.07.001. Epub 2019 Jul 30.

    PubMed 31375279

  • Sanda MG, Cadeddu JA, Kirkby E, Chen RC, Crispino T, Fontanarosa J, Freedland SJ, Greene K, Klotz LH, Makarov DV, Nelson JB, Rodrigues G, Sandler HM, Taplin ME, Treadwell JR. Clinically Localized Prostate Cancer: AUA/ASTRO/SUO Guideline. Part II: Recommended Approaches and Details of Specific Care Options. J Urol. 2018 Apr;199(4):990-997. doi: 10.1016/j.juro.2018.01.002. Epub 2018 Jan 10.

    PubMed 29331546

  • McClelland S 3rd, Sandler KA, Degnin C, Chen Y, Mitin T. Adjuvant vs. salvage radiation therapy in men with high-risk features after radical prostatectomy: Survey of North American genitourinary expert radiation oncologists. Can Urol Assoc J. 2019 May;13(5):E132-E134. doi: 10.5489/cuaj.5470. Epub 2018 Oct 15.

    PubMed 30332590

  • Ploussard G, Staerman F, Pierrevelcin J, Saad R, Beauval JB, Roupret M, Audenet F, Peyromaure M, Delongchamps NB, Vincendeau S, Fardoun T, Rigaud J, Villers A, Bastide C, Soulie M, Salomon L; Committee of Cancerology of the Association of French Urology. Predictive factors of oncologic outcomes in patients who do not achieve undetectable prostate specific antigen after radical prostatectomy. J Urol. 2013 Nov;190(5):1750-6. doi: 10.1016/j.juro.2013.04.073. Epub 2013 Apr 30.

    PubMed 23643600

  • Parker CC, Clarke NW, Cook AD, Kynaston HG, Petersen PM, Catton C, Cross W, Logue J, Parulekar W, Payne H, Persad R, Pickering H, Saad F, Anderson J, Bahl A, Bottomley D, Brasso K, Chahal R, Cooke PW, Eddy B, Gibbs S, Goh C, Gujral S, Heath C, Henderson A, Jaganathan R, Jakobsen H, James ND, Kanaga Sundaram S, Lees K, Lester J, Lindberg H, Money-Kyrle J, Morris S, O'Sullivan J, Ostler P, Owen L, Patel P, Pope A, Popert R, Raman R, Roder MA, Sayers I, Simms M, Wilson J, Zarkar A, Parmar MKB, Sydes MR. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial. Lancet. 2020 Oct 31;396(10260):1413-1421. doi: 10.1016/S0140-6736(20)31553-1. Epub 2020 Sep 28.

    PubMed 33002429

  • Vale CL, Fisher D, Kneebone A, Parker C, Pearse M, Richaud P, Sargos P, Sydes MR, Brawley C, Brihoum M, Brown C, Chabaud S, Cook A, Forcat S, Fraser-Browne C, Latorzeff I, Parmar MKB, Tierney JF; ARTISTIC Meta-analysis Group. Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data. Lancet. 2020 Oct 31;396(10260):1422-1431. doi: 10.1016/S0140-6736(20)31952-8. Epub 2020 Sep 28.

    PubMed 33002431

  • Sargos P, Chabaud S, Latorzeff I, Magne N, Benyoucef A, Supiot S, Pasquier D, Abdiche MS, Gilliot O, Graff-Cailleaud P, Silva M, Bergerot P, Baumann P, Belkacemi Y, Azria D, Brihoum M, Soulie M, Richaud P. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial. Lancet Oncol. 2020 Oct;21(10):1341-1352. doi: 10.1016/S1470-2045(20)30454-X.

    PubMed 33002438

  • Shipley WU, Seiferheld W, Lukka HR, Major PP, Heney NM, Grignon DJ, Sartor O, Patel MP, Bahary JP, Zietman AL, Pisansky TM, Zeitzer KL, Lawton CA, Feng FY, Lovett RD, Balogh AG, Souhami L, Rosenthal SA, Kerlin KJ, Dignam JJ, Pugh SL, Sandler HM; NRG Oncology RTOG. Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer. N Engl J Med. 2017 Feb 2;376(5):417-428. doi: 10.1056/NEJMoa1607529.

    PubMed 28146658

  • Carrie C, Magne N, Burban-Provost P, Sargos P, Latorzeff I, Lagrange JL, Supiot S, Belkacemi Y, Peiffert D, Allouache N, Dubray BM, Servagi-Vernat S, Suchaud JP, Crehange G, Guerif S, Brihoum M, Barbier N, Graff-Cailleaud P, Ruffion A, Dussart S, Ferlay C, Chabaud S. Short-term androgen deprivation therapy combined with radiotherapy as salvage treatment after radical prostatectomy for prostate cancer (GETUG-AFU 16): a 112-month follow-up of a phase 3, randomised trial. Lancet Oncol. 2019 Dec;20(12):1740-1749. doi: 10.1016/S1470-2045(19)30486-3. Epub 2019 Oct 16.

    PubMed 31629656

  • Fossati N, Robesti D, Karnes RJ, Soligo M, Boorjian SA, Bossi A, Coraggio G, Di Muzio N, Cozzarini C, Noris Chiorda B, Gandaglia G, Scarcella S, Bartkowiak D, Bohmer D, Shariat S, Goldner G, Battaglia A, Joniau S, Haustermans K, De Meerleer G, Fonteyne V, Ost P, Van Poppel H, Montorsi F, Wiegel T, Briganti A. Assessing the Role and Optimal Duration of Hormonal Treatment in Association with Salvage Radiation Therapy After Radical Prostatectomy: Results from a Multi-Institutional Study. Eur Urol. 2019 Oct;76(4):443-449. doi: 10.1016/j.eururo.2019.02.004. Epub 2019 Feb 22.

    PubMed 30799187

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Early salvage radiotherapy (eSRT) and Delayed Salvage radiotherapy (dSRT) in people with Prostate Cancer, run by General University Hospital, Prague.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 3 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sona Argalacsova, MD, PhD (+420224962219, sona.argalacsova@vfn.cz), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free survival (EFS) (time frame: Analysed 3 years after randomisation of the last patient.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05232578, which also lists 27 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in