Prostate CancerPhase 3URONCOR 06-24NCT05781217
Short Versus Long-term Androgen Deprivation Therapy With Salvage Radiotherapy in Prostate Cancer. URONCOR 0624
A Phase 3 study testing triptorelin, goserelin, leuprorelin in people with Prostate Cancer and Salvage Radiotherapy, run by Instituto de Investigación en Oncología Radioterápica - Fundación Española de Oncología Radioterápic at 17 sites in Spain.
Trial summary
The optimal indication for ADT has long been a point of controversy, at least until the results of randomised trials comparing RT with and without ADT were published. NCCN guidelines and most retrospective series and left the decision to prescribe ADT in combination with RT to the discretion of the treating physician… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Prostate Cancer, Salvage Radiotherapy, Biochemical Recurrence
- What is being tested?
- triptorelin, goserelin, leuprorelin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 534 participants
- Where
- 17 sitesSpain
- Study dates
- 14 Mar 2023to Dec 2032
- Phase
- Phase 3
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histologically-confirmed prostate cancer treated with radical prostatectomy. Patients who have not undergone lymph node dissection are eligible for inclusion.
- Biochemical recurrence after prostatectomy: BCR is defined as a PSA value ≥ 0.2 ng/mL, with at least one confirmatory PSA determination ≥ two weeks after the first test (the confirmatory PSA level must be higher than the initial value). Patients with Gleason 8-10, pT3b or R1 are eligible for inclusion in the trial with PSA ≥ 0.15 ng/mL; however, in patients with PSA > 0.4 ng/mL, imaging tests (conventional CT and bone scans or advanced imaging techniques such as PSMA or choline PET/CT) should be performed to check for metastases. In patients with PSA levels between 0.15 and 0.4 ng/mL, no further tests are required to check for distant metastases prior to inclusion.
- Intermediate and high-risk patients according to the classification criteria proposed by González San Segundo et al. (18):
- CHARACTERISTICS INTERMEDIATE RISK (≥ 2) HIGH RISK(≥ 1)
- PSA at diagnosis, ng/mL 0.6-1.0 ≥1.0 PSA doubling time, months 6-12 < 6 GLEASON / ISUP 7/3 ≥8/≥4 TNM (prostatectomy specimen) pT2-3a pN0-Mx pT3b pN0-Mx Time to biochemical recurrence, months >18 <18 Margins Positive Positive
- Testosterone level > 150 ng/dL at inclusion
Show all 9Show fewer
- ECOG 0-1
- Life expectancy > 5 years
- Signed informed consent
Who cannot join
- Presence of pN1 disease in the original surgical specimen
- Presence of macroscopic disease on imaging tests. If the PSA at diagnosis is > 0.4 ng/mL, then imaging tests (CT and bone scan and/or PET/CT or body magnetic resonance imaging [MRI]) are required.
- PSA <0.2 or <0.15 ng/mL (if Gleason score=10, pT3b, or R1 in the radical prostatectomy specimen).
- Previous pelvic radiotherapy
- Radiotherapy contraindicated
- Ongoing treatment with ADT or PSA-modulating drugs (e.g., finasteride, dutasteride, high dose steroids)
- Inability to understand the treatment protocol or sign informed consent
Trial locations and contacts
17 sites in 1 country. Contact the study team or a site near you to ask about taking part.
17 sites in 1 country
Spain17 sites, 14 recruiting
- Not yet recruiting
Hospital de Cruces
Barakaldo, Vizcaya, 48903
Alfonso Gómez, MD
- Not yet recruiting
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Xavier Maldonado, MD
- Not yet recruiting
Hospital Clinic de Barcelona
Barcelona, 08036
Joel Mases, MD
- Not yet recruiting
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
Gemma Sancho, MD
- Active, not recruiting
Hospital Universitario de Fuenlabrada
Fuenlabrada, Madrid, 28942
- Not yet recruiting
Instituto Catalán de Oncología Hospitalet
L'Hospitalet de Llobregat, Barcelona, 08908
Anna Maria Boladeras, MD
- Recruiting
Hospital San Francisco de Asís
Madrid, 28002
Felipe Couñago, MD
- Recruiting
Hospital Gregorio Marañón
Madrid, 28007
Carmen González, MD
- Recruiting
Hospital Ramón y Cajal
Madrid, 28034
Fernando López, MD
- Recruiting
Hospital Ruber Internacional
Madrid, 28034
Aurora Rodríguez, MD
- Not yet recruiting
Hospital Clínico San Carlos
Madrid, 28040
Noelia Sanmamed, MD
- Recruiting
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040
Jesús Oliveira, MD
- Not yet recruiting
Hospital Universitario de La Paz
Madrid, 28046
Luis Alberto Glaria, MD
- Active, not recruiting
Hospital Universitario HM Sanchinarro
Madrid, 28050
- Recruiting
Hospital Universitario Quirón Madrid
Pozuelo de Alarcón, Madrid, 28223
Victor Duque, MD
- Active, not recruiting
Hospital Universitario Sant Joan de Reus
Tarragona, 43204
- Not yet recruiting
Hospital Universitario y Politécnico de La Fe
Valencia, 46026
Antonio José Conde, MD
About this study
Official title: Short Versus Long-term Androgen Deprivation Therapy Combined With Salvage Radiotherapy in Prostate Cancer Patients With Biochemical Recurrence After Prostatectomy: a Multicentre Phase III Randomised Controlled Trial
The optimal indication for ADT has long been a point of controversy, at least until the results of randomised trials comparing RT with and without ADT were published. NCCN guidelines and most retrospective series and left the decision to prescribe ADT in combination with RT to the discretion of the treating physician, despite a lack of clear scientific evidence to support this recommendation. The percentage of patients in those retrospective series who received hormone therapy ranged from 33% to 71%, but generally involved patients with adverse prognostic factors (Gleason score > 7, stage pT3-T4, PSA > 1 ng/mL in cases with biochemical recurrence [BCR], and PSA doubling time [PSA-DT] < 6 months). Despite the heterogeneity in those studies in terms of treatment duration, RT dose, and treatment volumes, most of the studies found that ADT significantly prolonged biochemical relapse-free survival (BRFS), especially in patients with PSA levels > 1 ng/mL at recurrence.
The results of two randomised trials evaluating SRT with or without ADT were published in 2017, with both trials demonstrating a benefit for ADT in this clinical setting. A follow-up study confirmed the value of ADT in combination with SRT in terms of better PFS and, in the RTOG study, an improvement in overall survival (OS). Despite the lack of data from phase III trials regarding the influence of PSA-DT, the BRFS interval, and the Gleason score in terms of their effects on the clinical course of patients who develop BCR, there is strong evidence from other studies to support the use of these variables (together with age and comorbidities). Given the available evidence, we believe that these variables should be considered when determining the indications for ADT.
Read more
In line with the philosophy underlying the approach used by D'Amico to develop a risk classification system for prostate cancer patients at diagnosis, we propose three risk groups. According to Pollack et al. and Spratt et al., low-risk patients would not benefit from hormone therapy, especially long-term ADT, due to the deleterious effects of such treatment. By contrast, intermediate and high risk patients would be candidates for ADT combined with RT. However, the optimal duration of ADT in these patients (6 months vs. 2 years) remains undefined and needs to be determined prospectively in a randomised trial, similar to the approach used in the DART 05.01 trial.
SRT and ADT are widely used in routine clinical practice to treat patients who develop BCR after prostatectomy. In this context, we intend to perform a multicentre, phase III trial to define the optimal duration of ADT (6 vs. 24 months).
- Conditions
- Prostate Cancer, Salvage Radiotherapy, Biochemical Recurrence, Androgen Deprivation Therapy, Metastases-free Survival
- Being tested
- triptorelin, goserelin, leuprorelin
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
triptorelin, goserelin, leuprorelinDrug
ADT will consist of LHRH analogues (triptorelin, goserelin, leuprorelin) with bicalutamide 50 mg/day started 10 days before the first ADT injection to avoid LHRH-related flare-ups. Bicalutamide will be discontinued after 30 days. The LHRH analogue will be initiated prior to the start of radiotherapy and administered for 6 or 24 months depending on treatment allocation. The maximum time permitted between randomisation and administration of the first LHRH dose is 30 days. The maximum time from the first LHRH dose to the start of SRT is 60 days.
| Study group | Role | What they receive |
|---|---|---|
| short-term ADT (6 months) | Active comparator | ARM 1:
LHRH analogues for 6 months + bicalutamide 50 for 30 days Receives: Drug: triptorelin, goserelin, leuprorelin |
| long-term ADT (24 months) | Active comparator | LHRH analogues for 24 months + bicalutamide 50 for 30 days Receives: Drug: triptorelin, goserelin, leuprorelin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare 5-year MFS rates in prostate cancer patients treated with long- versus short-term ADT in combination with salvage radiotherapy
Distant metastasis-free survival: time from administration of the first LHRH analogue (this same starting point applies to all secondary objectives) until the patient develops M1a disease (involved retroperitoneal lymph nodes) or M1b-c disease (bone/visceral involvement) according to RECIST 1.1 criteria based on conventional computed tomography (CT) imaging and bone scans. The use of advanced molecular imaging-PSMA or choline positron-emission tomography (PET)/CT-is subject to the centre-specific protocols in place at the participating hospitals; however, metastatic progression will be determined according to RECIST 1.1 criteria based on conventional imaging tests.
Measured: 5 years
Secondary outcomes (9)
To compare the two study arms in terms of the Biochemical-relapse free interval
BRFS: time to biochemical progression defined as an increase in PSA confirmed by a second PSA determination (0.2 ng/mL above the salvage radiotherapy nadir or a sustained elevation in PSA levels).
Measured: 5 years
To compare the two study arms in terms of the Pelvic progression-free survival
Pelvic PFS: time to local recurrence (prostate bed) and/or N1 disease (positive lymph nodes below the aortic bifurcation) according to RECIST 1.1 criteria by conventional CT imaging and bone scan. The use of advanced molecular imaging (PSMA or choline PET/CT) will depend on centre-specific protocols; determination of metastatic progression will be based on RECIST 1.1 criteria from conventional imaging tests.
Measured: 5 years
To compare the two study arms in terms of the Time to start of cytotoxic treatment
Cytotoxic treatment-free interval: time to the start of the first cytotoxic treatment or local treatment for oligorecurrence.
Measured: 5 years
To compare the two study arms in terms of the Time to castration resistance
Time interval to castration resistance: the time to biochemical and/or clinical progression with castration levels (testosterone < 50 ng/dL). Progression to castration resistance is defined as three consecutive increases in PSA (one-week intervals) with at least two PSA increases > 2 ng/mL and a 50% increase over the PSA nadir, progression of bone lesions (≥ two lesions on the bone scan), progression of soft tissue lesions (RECIST 1.1 criteria), or the development of ≥ one soft tissue or visceral metastases (including lymph nodes).
Measured: 5 years
To compare the two study arms in terms of the Cancer-specific survival
time to death due to prostate cancer or treatment-related complications
Measured: 5 years
To compare the two study arms in terms of the Overall survival
time to death from any cause
Measured: 5 years
To compare the two study arms in terms of the Acute and late toxicity
Acute toxicity: toxicity (CTCAE criteria, v. 4.0; https://evs.nci.nih.gov) appearing any time from treatment initiation up to three months after completion of RT.
Measured: 5 years
To compare the two study arms in terms of the Late toxicity
-Late toxicity: from 3 months to 5 years after completing RT (CTCAE v 4.0).
Measured: 5 years
To compare the two study arms in terms of Quality of life (QoL)
Quality of life (QoL): from baseline (prior to RT) to five years after completion of RT, assessed with the EORTC QLQ-C30 and QLQ-PR25 questionnaires.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2023
- Study start14 Mar 2023
- Primary completionDec 2023 (estimated)
- Study completionDec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Masking
- None (open label)
- Enrolment
- 534 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto de Investigación en Oncología Radioterápica - Fundación Española de Oncología Radioterápic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05781217
- Sponsor's protocol ID
- URONCOR 06-24
- Acronym
- URONCOR 06-24
- Status last verified
- Nov 2023
- First submitted
- 24 Feb 2023
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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 33002429Sargos 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 33002438Kneebone 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 33002437Vale 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 33002431Lieng H, Hayden AJ, Christie DRH, Davis BJ, Eade TN, Emmett L, Holt T, Hruby G, Pryor D, Shakespeare TP, Sidhom M, Skala M, Wiltshire K, Yaxley J, Kneebone A. Radiotherapy for recurrent prostate cancer: 2018 Recommendations of the Australian and New Zealand Radiation Oncology Genito-Urinary group. Radiother Oncol. 2018 Nov;129(2):377-386. doi: 10.1016/j.radonc.2018.06.027. Epub 2018 Jul 20.
PubMed 30037499Shipley 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 28146658Carrie C, Hasbini A, de Laroche G, Richaud P, Guerif S, Latorzeff I, Supiot S, Bosset M, Lagrange JL, Beckendorf V, Lesaunier F, Dubray B, Wagner JP, N'Guyen TD, Suchaud JP, Crehange G, Barbier N, Habibian M, Ferlay C, Fourneret P, Ruffion A, Dussart S. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol. 2016 Jun;17(6):747-756. doi: 10.1016/S1470-2045(16)00111-X. Epub 2016 May 6.
PubMed 27160475Valicenti RK, Thompson I Jr, Albertsen P, Davis BJ, Goldenberg SL, Wolf JS, Sartor O, Klein E, Hahn C, Michalski J, Roach M 3rd, Faraday MM; American Society for Radiation Oncology/American Urological Association. Adjuvant and salvage radiation therapy after prostatectomy: American Society for Radiation Oncology/American Urological Association guidelines. Int J Radiat Oncol Biol Phys. 2013 Aug 1;86(5):822-8. doi: 10.1016/j.ijrobp.2013.05.029.
PubMed 23845839Fossati N, Karnes RJ, Boorjian SA, Moschini M, Morlacco A, Bossi A, Seisen T, Cozzarini C, Fiorino C, Noris Chiorda B, Gandaglia G, Dell'Oglio P, Joniau S, Tosco L, Shariat S, Goldner G, Hinkelbein W, Bartkowiak D, Haustermans K, Tombal B, Montorsi F, Van Poppel H, Wiegel T, Briganti A. Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0 Prostate Cancer Patients Treated with Radical Prostatectomy: Results from a Multi-institutional Series. Eur Urol. 2017 Jun;71(6):886-893. doi: 10.1016/j.eururo.2016.07.028. Epub 2016 Jul 30.
PubMed 27484843Spratt DE, Dess RT, Zumsteg ZS, Lin DW, Tran PT, Morgan TM, Antonarakis ES, Nguyen PL, Ryan CJ, Sandler HM, Cooperberg MR, Posadas E, Feng FY. A Systematic Review and Framework for the Use of Hormone Therapy with Salvage Radiation Therapy for Recurrent Prostate Cancer. Eur Urol. 2018 Feb;73(2):156-165. doi: 10.1016/j.eururo.2017.06.027. Epub 2017 Jul 14.
PubMed 28716370Gonzalez-San Segundo C, Counago F, Gomez-Iturriaga A. Androgen Deprivation Therapy and Salvage Radiotherapy: Are We Missing Something? Eur Urol. 2019 Aug;76(2):260-261. doi: 10.1016/j.eururo.2019.01.045. Epub 2019 Feb 8. No abstract available.
PubMed 30745145Jia ZW, Chang K, Dai B, Kong YY, Wang Y, Qu YY, Zhu YP, Ye DW. Factors influencing biochemical recurrence in patients who have received salvage radiotherapy after radical prostatectomy: a systematic review and meta-analysis. Asian J Androl. 2017 Jul-Aug;19(4):493-499. doi: 10.4103/1008-682X.179531.
PubMed 27241314Carrie 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 31629656Dess RT, Sun Y, Jackson WC, Jairath NK, Kishan AU, Wallington DG, Mahal BA, Stish BJ, Zumsteg ZS, Den RB, Hall WA, Gharzai LA, Jaworski EM, Reichert ZR, Morgan TM, Mehra R, Schaeffer EM, Sartor O, Nguyen PL, Lee WR, Rosenthal SA, Michalski JM, Schipper MJ, Dignam JJ, Pisansky TM, Zietman AL, Sandler HM, Efstathiou JA, Feng FY, Shipley WU, Spratt DE. Association of Presalvage Radiotherapy PSA Levels After Prostatectomy With Outcomes of Long-term Antiandrogen Therapy in Men With Prostate Cancer. JAMA Oncol. 2020 May 1;6(5):735-743. doi: 10.1001/jamaoncol.2020.0109.
PubMed 32215583Pollack A, Karrison TG, Balogh AG, Gomella LG, Low DA, Bruner DW, Wefel JS, Martin AG, Michalski JM, Angyalfi SJ, Lukka H, Faria SL, Rodrigues GB, Beauchemin MC, Lee RJ, Seaward SA, Allen AM, Monitto DC, Seiferheld W, Sartor O, Feng F, Sandler HM. The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial. Lancet. 2022 May 14;399(10338):1886-1901. doi: 10.1016/S0140-6736(21)01790-6.
PubMed 35569466