Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trial
Abstract Background Recent retrospective data suggest that neoadjuvant androgen deprivation therapy can improve the prognosis of high-risk prostate cancer (PCa) patients. Novel androgen receptor pathway inhibitors are nowadays available for treatment of metastatic PCa and these compounds are promisi...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-04-01
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| Series: | BMC Cancer |
| Online Access: | http://link.springer.com/article/10.1186/s12885-018-4275-z |
| _version_ | 1828432670743330816 |
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| author | Lorenzo Tosco Annouschka Laenen Thomas Gevaert Isabelle Salmon Christine Decaestecker Elai Davicioni Christine Buerki Frank Claessens Johan Swinnen Karolien Goffin Raymond Oyen Wouter Everaerts Lisa Moris Gert De Meerleer Karin Haustermans Steven Joniau P.E.A.R.L. (ProstatE cAncer Research Leuven) |
| author_facet | Lorenzo Tosco Annouschka Laenen Thomas Gevaert Isabelle Salmon Christine Decaestecker Elai Davicioni Christine Buerki Frank Claessens Johan Swinnen Karolien Goffin Raymond Oyen Wouter Everaerts Lisa Moris Gert De Meerleer Karin Haustermans Steven Joniau P.E.A.R.L. (ProstatE cAncer Research Leuven) |
| author_sort | Lorenzo Tosco |
| collection | DOAJ |
| description | Abstract Background Recent retrospective data suggest that neoadjuvant androgen deprivation therapy can improve the prognosis of high-risk prostate cancer (PCa) patients. Novel androgen receptor pathway inhibitors are nowadays available for treatment of metastatic PCa and these compounds are promising for early stage disease. Apalutamide is a pure androgen antagonist with a very high affinity with the androgen receptor. The combination of apalutamide with degarelix, an LHRH antagonist, could increase the efficacy compared to degarelix alone. Objective The primary objective is to assess the difference in proportions of minimal residual disease at prostatectomy specimen between apalutamide + degarelix vs placebo + degarelix. Various secondary endpoints are assessed: variations of different biomarkers at the tumour level (tissue microarrays to evaluate DNA-PKs, PARP, AR and splice variants, PSMA, etc.), whole transcriptome sequencing, exome sequencing and clinical (PSA and testosterone kinetics, early biochemical recurrence free survival, quality of life, safety, etc.) and radiological endpoints. Methods ARNEO is a single centre, phase II, randomized, double blind, placebo-controlled trial. The plan is to include at least 42 patients per each of the two study arms. Patients with intermediate/high-risk PCa and who are amenable for radical prostatectomy with pelvic lymph node dissection can be included. After signing an informed consent, every patient will undergo a pelvic 68Ga -PSMA-11 PSMA PET/MR and receive degarelix at standard dosage and start assuming apalutamide/placebo (60 mg 4 tablets/day) for 12 weeks. Within thirty days from the last study medication intake the same imaging will be repeated. Every patient will undergo PSA and testosterone testing the day of randomization, before the first drug intake, and after the last dose. Formalin fixed paraffin embedded tumour samples will be collected and used for transcriptome analysis, exome sequencing and immunohistochemistry. Discussion ARNEO will allow us to answer, first, whether the combined treatment can result in an increased proportion of patients with minimal residual disease. Secondly, It will enable the study of the molecular consequences at the level of the tumour. Thirdly, what the consequences are of new generation androgen receptor pathway inhibitors on 68Ga -PSMA-11 PET/MR. Finally, various clinical, safety and quality of life data will be collected. Trial Registration EUDRaCT number: 2016–002854-19 (authorization date 3rd August 2017). clinicalTrial.gov: NCT03080116. |
| first_indexed | 2024-12-10T18:23:04Z |
| format | Article |
| id | doaj.art-d756a2c91f6b4917b75eee73727709ee |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-10T18:23:04Z |
| publishDate | 2018-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-d756a2c91f6b4917b75eee73727709ee2022-12-22T01:38:09ZengBMCBMC Cancer1471-24072018-04-0118111010.1186/s12885-018-4275-zNeoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trialLorenzo Tosco0Annouschka Laenen1Thomas Gevaert2Isabelle Salmon3Christine Decaestecker4Elai Davicioni5Christine Buerki6Frank Claessens7Johan Swinnen8Karolien Goffin9Raymond Oyen10Wouter Everaerts11Lisa Moris12Gert De Meerleer13Karin Haustermans14Steven Joniau15P.E.A.R.L. (ProstatE cAncer Research Leuven)Urology, Department of Development and Regeneration, University Hospitals LeuvenLeuven Biostatistics and Statistical Bioinformatics Center, KU LeuvenLaboratory of Experimental Urology, Organ Systems, KU LeuvenDIAPath, Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles (ULB)DIAPath, Center for Microscopy and Molecular Imaging, Université Libre de Bruxelles (ULB)GenomeDX, Biosciences IncGenomeDX, Biosciences IncKU Leuven, Department of Cellular and Molecular Medicine, Laboratory of Molecular EndocrinologyLaboratory of Lipid Metabolism and Cancer, Department of Oncology, KU LeuvenDepartment of Imaging and Pathology, KU LeuvenDepartment of Radiology Gasthuisberg University Hospitals LeuvenUrology, Department of Development and Regeneration, University Hospitals LeuvenKU Leuven, Department of Cellular and Molecular Medicine, Laboratory of Molecular EndocrinologyDepartment of Radiation Oncology, University Hospitals LeuvenDepartment of Radiation Oncology, University Hospitals LeuvenUrology, Department of Development and Regeneration, University Hospitals LeuvenAbstract Background Recent retrospective data suggest that neoadjuvant androgen deprivation therapy can improve the prognosis of high-risk prostate cancer (PCa) patients. Novel androgen receptor pathway inhibitors are nowadays available for treatment of metastatic PCa and these compounds are promising for early stage disease. Apalutamide is a pure androgen antagonist with a very high affinity with the androgen receptor. The combination of apalutamide with degarelix, an LHRH antagonist, could increase the efficacy compared to degarelix alone. Objective The primary objective is to assess the difference in proportions of minimal residual disease at prostatectomy specimen between apalutamide + degarelix vs placebo + degarelix. Various secondary endpoints are assessed: variations of different biomarkers at the tumour level (tissue microarrays to evaluate DNA-PKs, PARP, AR and splice variants, PSMA, etc.), whole transcriptome sequencing, exome sequencing and clinical (PSA and testosterone kinetics, early biochemical recurrence free survival, quality of life, safety, etc.) and radiological endpoints. Methods ARNEO is a single centre, phase II, randomized, double blind, placebo-controlled trial. The plan is to include at least 42 patients per each of the two study arms. Patients with intermediate/high-risk PCa and who are amenable for radical prostatectomy with pelvic lymph node dissection can be included. After signing an informed consent, every patient will undergo a pelvic 68Ga -PSMA-11 PSMA PET/MR and receive degarelix at standard dosage and start assuming apalutamide/placebo (60 mg 4 tablets/day) for 12 weeks. Within thirty days from the last study medication intake the same imaging will be repeated. Every patient will undergo PSA and testosterone testing the day of randomization, before the first drug intake, and after the last dose. Formalin fixed paraffin embedded tumour samples will be collected and used for transcriptome analysis, exome sequencing and immunohistochemistry. Discussion ARNEO will allow us to answer, first, whether the combined treatment can result in an increased proportion of patients with minimal residual disease. Secondly, It will enable the study of the molecular consequences at the level of the tumour. Thirdly, what the consequences are of new generation androgen receptor pathway inhibitors on 68Ga -PSMA-11 PET/MR. Finally, various clinical, safety and quality of life data will be collected. Trial Registration EUDRaCT number: 2016–002854-19 (authorization date 3rd August 2017). clinicalTrial.gov: NCT03080116.http://link.springer.com/article/10.1186/s12885-018-4275-z |
| spellingShingle | Lorenzo Tosco Annouschka Laenen Thomas Gevaert Isabelle Salmon Christine Decaestecker Elai Davicioni Christine Buerki Frank Claessens Johan Swinnen Karolien Goffin Raymond Oyen Wouter Everaerts Lisa Moris Gert De Meerleer Karin Haustermans Steven Joniau P.E.A.R.L. (ProstatE cAncer Research Leuven) Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trial BMC Cancer |
| title | Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trial |
| title_full | Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trial |
| title_fullStr | Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trial |
| title_full_unstemmed | Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trial |
| title_short | Neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high-risk prostate cancer: ARNEO, a randomized, double blind, placebo-controlled trial |
| title_sort | neoadjuvant degarelix with or without apalutamide followed by radical prostatectomy for intermediate and high risk prostate cancer arneo a randomized double blind placebo controlled trial |
| url | http://link.springer.com/article/10.1186/s12885-018-4275-z |
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