Update to a randomized controlled trial of lutetium-177-PSMA in Oligo-metastatic hormone-sensitive prostate cancer: the BULLSEYE trial

Bastiaan M Privé, Marcel J R Janssen, Inge M van Oort, Constantijn H J Muselaers, Marianne A Jonker, Willemijn A van Gemert, Michel de Groot, Harm Westdorp, Niven Mehra, J Fred Verzijlbergen, Tom W J Scheenen, Patrik Zámecnik, Jelle O Barentsz, Martin Gotthardt, Walter Noordzij, Wouter V Vogel, Andries M Bergman, Henk G van der Poel, André N Vis, Daniela E Oprea-Lager, Winald R Gerritsen, J Alfred Witjes, James Nagarajah, Bastiaan M Privé, Marcel J R Janssen, Inge M van Oort, Constantijn H J Muselaers, Marianne A Jonker, Willemijn A van Gemert, Michel de Groot, Harm Westdorp, Niven Mehra, J Fred Verzijlbergen, Tom W J Scheenen, Patrik Zámecnik, Jelle O Barentsz, Martin Gotthardt, Walter Noordzij, Wouter V Vogel, Andries M Bergman, Henk G van der Poel, André N Vis, Daniela E Oprea-Lager, Winald R Gerritsen, J Alfred Witjes, James Nagarajah

Abstract

Background: The BULLSEYE trial is a multicenter, open-label, randomized controlled trial to test the hypothesis if 177Lu-PSMA is an effective treatment in oligometastatic hormone-sensitive prostate cancer (oHSPC) to prolong the progression-free survival (PFS) and postpone the need for androgen deprivation therapy (ADT). The original study protocol was published in 2020. Here, we report amendments that have been made to the study protocol since the commencement of the trial.

Changes in methods and materials: Two important changes were made to the original protocol: (1) the study will now use 177Lu-PSMA-617 instead of 177Lu-PSMA-I&T and (2) responding patients with residual disease on 18F-PSMA PET after the first two cycles are eligible to receive additional two cycles of 7.4 GBq 177Lu-PSMA in weeks 12 and 18, summing up to a maximum of 4 cycles if indicated. Therefore, patients receiving 177Lu-PSMA-617 will also receive an interim 18F-PSMA PET scan in week 4 after cycle 2. The title of this study was modified to; "Lutetium-177-PSMA in Oligo-metastatic Hormone Sensitive Prostate Cancer" and is now partly supported by Advanced Accelerator Applications, a Novartis Company.

Conclusions: We present an update of the original study protocol prior to the completion of the study. Treatment arm patients that were included and received 177Lu-PSMA-I&T under the previous protocol will be replaced.

Trial registration: ClinicalTrials.gov NCT04443062 . First posted: June 23, 2020.

Keywords: Hormone-sensitive prostate cancer; Lutetium-177-PSMA; Metastases-directed therapy; Oligometastases; Radioligand therapy; Urologic oncology.

Conflict of interest statement

JN receives research support from ABX Pharmaceuticals and Advanced Accelerator Applications.

© 2021. The Author(s).

References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. doi: 10.3322/caac.21492.
    1. Cornford P, van den Bergh RCN, Briers E, Van den Broeck T, Cumberbatch MG, De Santis M, Fanti S, Fossati N, Gandaglia G, Gillessen S, et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II—2020 Update: Treatment of Relapsing and Metastatic Prostate Cancer. Eur Urol. 2021;79(2):263–282. doi: 10.1016/j.eururo.2020.09.046.
    1. Freedland SJ, Eastham J, Shore N. Androgen deprivation therapy and estrogen deficiency induced adverse effects in the treatment of prostate cancer. Prostate Cancer Prostatic Dis. 2009;12(4):333–338. doi: 10.1038/pcan.2009.35.
    1. Zhou P, Chen MH, McLeod D, Carroll PR, Moul JW, D'Amico AV. Predictors of prostate cancer-specific mortality after radical prostatectomy or radiation therapy. J Clin Oncol. 2005;23(28):6992–6998. doi: 10.1200/JCO.2005.01.2906.
    1. Cornford P, Bellmunt J, Bolla M, Briers E, De Santis M, Gross T, Henry AM, Joniau S, Lam TB, Mason MD, et al. EAU-ESTRO-SIOG guidelines on prostate cancer. Part II: treatment of relapsing, metastatic, and castration-resistant prostate cancer. Eur Urol. 2017;71(4):630–642. doi: 10.1016/j.eururo.2016.08.002.
    1. Ahmadi H, Daneshmand S. Androgen deprivation therapy: evidence-based management of side effects. BJU Int. 2013;111(4):543–548. doi: 10.1111/j.1464-410X.2012.11774.x.
    1. Deek MP, Taparra K, Dao D, Chan L, Phillips R, Gao RW, Kwon ED, Deville C, Song DY, Greco S, et al. Patterns of recurrence and modes of progression after metastasis-directed therapy in oligometastatic castration-sensitive prostate cancer. Int J Radiat Oncol Biol Phys. 2021;109(2):387–395. doi: 10.1016/j.ijrobp.2020.08.030.
    1. Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, Bruycker AD, Lambert B, Delrue L, Bultijnck R, Goetghebeur E, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence (STOMP): five-year results of a randomized phase II trial. J Clin Oncol. 2020;38(6_suppl):10. doi: 10.1200/JCO.2020.38.6_suppl.10.
    1. Phillips R, Shi WY, Deek M, Radwan N, Lim SJ, Antonarakis ES, Rowe SP, Ross AE, Gorin MA, Deville C, Greco SC, Wang H, Denmeade SR, Paller CJ, Dipasquale S, DeWeese TL, Song DY, Wang H, Carducci MA, Pienta KJ, Pomper MG, Dicker AP, Eisenberger MA, Alizadeh AA, Diehn M, Tran PT. Outcomes of observation vs stereotactic ablative radiation for oligometastatic prostate cancer: the ORIOLE phase 2 randomized clinical trial. JAMA Oncol. 2020;6(5):650–659. doi: 10.1001/jamaoncol.2020.0147.
    1. Schmidt-Hegemann NS, Kroeze SGC, Henkenberens C, Vogel MME, Kirste S, Becker J, Burger IA, Derlin T, Bartenstein P, Eiber M, Mix M, la Fougère C, Müller AC, Grosu AL, Combs SE, Christiansen H, Guckenberger M, Belka C. Influence of localization of PSMA-positive oligo-metastases on efficacy of metastasis-directed external-beam radiotherapy-a multicenter retrospective study. Eur J Nucl Med Mol Imaging. 2020;47(8):1852–1863. doi: 10.1007/s00259-020-04708-y.
    1. Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, De Bruycker A, Lambert B, Delrue L, Bultijnck R, Claeys T, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, multicenter phase II trial. J Clin Oncol. 2018;36(5):446–453. doi: 10.1200/JCO.2017.75.4853.
    1. Tosoian JJ, Gorin MA, Ross AE, Pienta KJ, Tran PT, Schaeffer EM. Oligometastatic prostate cancer: definitions, clinical outcomes, and treatment considerations. Nat Rev Urol. 2017;14(1):15–25. doi: 10.1038/nrurol.2016.175.
    1. Lecouvet FE, Oprea-Lager DE, Liu Y, Ost P, Bidaut L, Collette L, Deroose CM, Goffin K, Herrmann K, Hoekstra OS, Kramer G, Lievens Y, Lopci E, Pasquier D, Petersen LJ, Talbot JN, Zacho H, Tombal B, deSouza NM. Use of modern imaging methods to facilitate trials of metastasis-directed therapy for oligometastatic disease in prostate cancer: a consensus recommendation from the EORTC Imaging Group. Lancet Oncol. 2018;19(10):e534–e545. doi: 10.1016/S1470-2045(18)30571-0.
    1. Hofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multi-centre study. Lancet.
    1. Schilham MG, Zamecnik P, Privé BM, Israël B, Rijpkema M, Scheenen T, et al. Head-to-head comparison of <sup>68</sup>Ga-prostate-specific membrane antigen PET/CT and ferumoxtran-10 enhanced MRI for the diagnosis of lymph node metastases in prostate cancer patients. J Nucl Med. 2021;jnumed.120.258541.
    1. Privé BM, Israël B, Schilham MGM, Muselaers CHJ, Zámecnik P, Mulders PFA, Witjes JA, Sedelaar M, Mehra N, Verzijlbergen F, Janssen MJR, Gotthardt M, Barentsz JO, van Oort IM, Nagarajah J. Evaluating F-18-PSMA-1007-PET in primary prostate cancer and comparing it to multi-parametric MRI and histopathology. Prostate Cancer Prostatic Dis. 2020;24(2):423–430. doi: 10.1038/s41391-020-00292-2.
    1. Privé B, Peters S, Muselaers C, Zamecnik P, Janssen M, Scheenen T, et al. Lutetium-177-PSMA-617 in low-volume hormone sensitive metastatic prostate cancer: a prospective study. 2020;59.
    1. Peters SMB, Privé BM, de Bakker M, de Lange F, Jentzen W, Eek A, et al. Intra-therapeutic dosimetry of [177Lu]Lu-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer patients and correlation with treatment outcome. Eur J Nucl Med Mol Imaging. 2021. 10.1007/s00259-021-05471-4.
    1. Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, et al. [<sup>177</sup>Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021;397(10276):797–804. doi: 10.1016/S0140-6736(21)00237-3.
    1. Violet J, Jackson P, Ferdinandus J, Sandhu S, Akhurst T, Iravani A, Kong G, Kumar AR, Thang SP, Eu P, Scalzo M, Murphy D, Williams S, Hicks RJ, Hofman MS. Dosimetry of (177)Lu-PSMA-617 in metastatic castration-resistant prostate cancer: correlations between pretherapeutic imaging and whole-body tumor dosimetry with treatment outcomes. J Nucl Med. 2019;60(4):517–523. doi: 10.2967/jnumed.118.219352.
    1. Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, et al. Lutetium-177–PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091–1103. doi: 10.1056/NEJMoa2107322.
    1. Privé BM, Slootbeek PHJ, Laarhuis BI, Naga SP, van der Doelen MJ, van Kalmthout LWM, et al. Impact of DNA damage repair defects on response to PSMA radioligand therapy in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis. 2021. 10.1038/s41391-021-00424-2.
    1. O'Donoghue JA, Bardies M, Wheldon TE. Relationships between tumor size and curability for uniformly targeted therapy with beta-emitting radionuclides. J Nucl Med. 1995;36(10):1902–1909.
    1. Privé BM, Janssen MJR, van Oort IM, Muselaers CHJ, Jonker MA, de Groot M, Mehra N, Verzijlbergen JF, Scheenen TWJ, Zámecnik P, Barentsz JO, Gotthardt M, Noordzij W, Vogel WV, Bergman AM, van der Poel HG, Vis AN, Oprea-Lager DE, Gerritsen WR, Witjes JA, Nagarajah J. Lutetium-177-PSMA-I&T as metastases directed therapy in oligometastatic hormone sensitive prostate cancer, a randomized controlled trial. BMC Cancer. 2020;20(1):884. doi: 10.1186/s12885-020-07386-z.

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