A randomized phase III trial of stereotactic ablative radiotherapy for patients with up to 10 oligometastases and a synchronous primary tumor (SABR-SYNC): study protocol.
Oligometastases
Quality of life
Stereotactic ablative radiotherapy
Synchronous
Journal
BMC palliative care
ISSN: 1472-684X
Titre abrégé: BMC Palliat Care
Pays: England
ID NLM: 101088685
Informations de publication
Date de publication:
07 Sep 2024
07 Sep 2024
Historique:
received:
07
06
2024
accepted:
16
08
2024
medline:
8
9
2024
pubmed:
8
9
2024
entrez:
7
9
2024
Statut:
epublish
Résumé
Emerging randomized data, mostly from phase II trials, have suggested that patients with oligometastatic cancers may benefit from ablative treatments such as stereotactic ablative radiotherapy (SABR). However, phase III data testing this paradigm are lacking, and many studies have examined SABR in the setting of metachronous oligometastatic disease. The goal of the SABR-SYNC trial is to assess the effect of SABR in patients with oligometastatic cancers and a synchronous primary tumor. One hundred and eighty patients will be randomized in a 1:2 ratio between standard of care (SOC) palliative-intent treatments vs. SOC + ablative therapy (SABR preferred) to all sites of known disease. Randomization will be stratified based on histology and number of metastases at enrollment. SABR may be delivered in 1-, 3- and 5-fraction regimens, with recommended doses of 20 Gy, 30 Gy, and 35 Gy, respectively. Non-SABR local modalities (e.g. surgery, thermal ablation, conventional radiation) may be used for treatment of the primary or metastases at the discretion of the treating physicians, if those modalities are clinically preferred. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, time to initiation of next systemic therapy, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor DNA and immunological predictors of outcomes. SABR-SYNC will provide phase III data to assess the impact of SABR on overall survival in a population of patients with synchronous oligometastases. The translational component will attempt to identify novel prognostic and predictive biomarkers to aid in clinical decision making. Clinicaltrials.gov NCT05717166 (registration date: Feb. 8, 2023).
Sections du résumé
BACKGROUND
BACKGROUND
Emerging randomized data, mostly from phase II trials, have suggested that patients with oligometastatic cancers may benefit from ablative treatments such as stereotactic ablative radiotherapy (SABR). However, phase III data testing this paradigm are lacking, and many studies have examined SABR in the setting of metachronous oligometastatic disease. The goal of the SABR-SYNC trial is to assess the effect of SABR in patients with oligometastatic cancers and a synchronous primary tumor.
METHODS
METHODS
One hundred and eighty patients will be randomized in a 1:2 ratio between standard of care (SOC) palliative-intent treatments vs. SOC + ablative therapy (SABR preferred) to all sites of known disease. Randomization will be stratified based on histology and number of metastases at enrollment. SABR may be delivered in 1-, 3- and 5-fraction regimens, with recommended doses of 20 Gy, 30 Gy, and 35 Gy, respectively. Non-SABR local modalities (e.g. surgery, thermal ablation, conventional radiation) may be used for treatment of the primary or metastases at the discretion of the treating physicians, if those modalities are clinically preferred. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, time to initiation of next systemic therapy, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor DNA and immunological predictors of outcomes.
DISCUSSION
CONCLUSIONS
SABR-SYNC will provide phase III data to assess the impact of SABR on overall survival in a population of patients with synchronous oligometastases. The translational component will attempt to identify novel prognostic and predictive biomarkers to aid in clinical decision making.
TRIAL REGISTRATION
BACKGROUND
Clinicaltrials.gov NCT05717166 (registration date: Feb. 8, 2023).
Identifiants
pubmed: 39244532
doi: 10.1186/s12904-024-01548-7
pii: 10.1186/s12904-024-01548-7
doi:
Banques de données
ClinicalTrials.gov
['NCT05717166']
Types de publication
Journal Article
Clinical Trial, Phase III
Randomized Controlled Trial
Clinical Trial Protocol
Langues
eng
Sous-ensembles de citation
IM
Pagination
223Informations de copyright
© 2024. The Author(s).
Références
Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol Off J Am Soc Clin Oncol. 1995;13(1):8–10.
doi: 10.1200/JCO.1995.13.1.8
Palma DA, Olson R, Harrow S, Correa RJM, Schneiders F, Haasbeek CJA, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of 4–10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial. BMC Cancer. 2019;19(1):816.
doi: 10.1186/s12885-019-5977-6
pubmed: 31426760
pmcid: 6699121
Bauman GS, Corkum MT, Fakir H, Nguyen TK, Palma DA. Ablative radiation therapy to restrain everything safely treatable (ARREST): study protocol for a phase I trial treating polymetastatic cancer with stereotactic radiotherapy. BMC Cancer. 2021;21(1):405.
doi: 10.1186/s12885-021-08020-2
pubmed: 33853550
pmcid: 8048078
Olson R, Mathews L, Liu M, Schellenberg D, Mou B, Berrang T, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of 1–3 Oligometastatic tumors (SABR-COMET-3): study protocol for a randomized phase III trial. BMC Cancer. 2020;20(1):380.
doi: 10.1186/s12885-020-06876-4
pubmed: 32370765
pmcid: 7201684
Ashworth AB, Senan S, Palma DA, Riquet M, Ahn YC, Ricardi U, et al. An individual patient data metaanalysis of outcomes and prognostic factors after treatment of oligometastatic non-small-cell lung cancer. Clin Lung Cancer. 2014;15(5):346–55.
doi: 10.1016/j.cllc.2014.04.003
pubmed: 24894943
Gomez DR, Tang C, Zhang J, Blumenschein GR, Hernandez M, Lee JJ, et al. Local consolidative therapy Vs. Maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer: long-term results of a multi-institutional, phase II, randomized study. J Clin Oncol Off J Am Soc Clin Oncol. 2019;37(18):1558–65.
doi: 10.1200/JCO.19.00201
Iyengar P, Wardak Z, Gerber DE, Tumati V, Ahn C, Hughes RS, et al. Consolidative radiotherapy for limited metastatic non-small-cell lung cancer: A phase 2 randomized clinical trial. JAMA Oncol. 2018;4(1):e173501.
doi: 10.1001/jamaoncol.2017.3501
pubmed: 28973074
Ost P, Reynders D, Decaestecker K, Fonteyne V, Lumen N, De Bruycker A, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, multicenter phase II Trial. J Clin Oncol Off J Am Soc Clin Oncol. 2018;36(5):446–53.
doi: 10.1200/JCO.2017.75.4853
Phillips R, Shi WY, Deek M, Radwan N, Lim SJ, Antonarakis ES, et al. Outcomes of observation vs Stereotactic ablative radiation for oligometastatic prostate cancer: The ORIOLE phase 2 randomized clinical trial. JAMA Oncol. 2020;6(5):650–9.
doi: 10.1001/jamaoncol.2020.0147
pubmed: 32215577
pmcid: 7225913
Wang XS, Bai YF, Verma V, Yu RL, Tian W, Ao R, Deng Y, Zhu XQ, Liu H, Pan HX, Yang L, Bai HS, Luo X, Guo Y, Zhou MX, Sun YM, Zhang ZC, Li SM, Cheng X, Tan BX, Han LF, Liu YY, Zhang K, Zeng FX, Jia L, Hao XB, Wang YY, Feng G, Xie K, Lu Y, Zeng M. Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer. J Natl Cancer Inst.2023;115(6):742–8. https://doi.org/10.1093/jnci/djac015 . Erratum in: J Natl Cancer Inst. 2023;115(6):773. https://doi.org/10.1093/jnci/djad084 .
Peng P, Gong J, Zhang Y, Zhou S, Li Y, Han G, et al. EGFR-TKIs plus stereotactic body radiation therapy (SBRT) for stage IV Non-small cell lung cancer (NSCLC): A prospective, multicenter, randomized, controlled phase II study. Radiother Oncol. 2023;184. Available from: https://www.thegreenjournal.com/article/S0167-8140(23)00219-0/fulltext . Cited 2023 Dec 28.
Tang C, Sherry AD, Haymaker C, Bathala T, Liu S, Fellman B, et al. Addition of Metastasis-Directed Therapy to Intermittent Hormone Therapy for Oligometastatic Prostate Cancer: The EXTEND Phase 2 Randomized Clinical Trial. JAMA Oncol. 2023;9(6):825–34.
doi: 10.1001/jamaoncol.2023.0161
pubmed: 37022702
pmcid: 10080407
Francolini G, Allegra AG, Detti B, Di Cataldo V, Caini S, Bruni A, Ingrosso G, et al. Stereotactic Body Radiation Therapy and Abiraterone Acetate for Patients Affected by Oligometastatic Castrate-Resistant Prostate Cancer: A Randomized Phase II Trial (ARTO). J Clin Oncol. 2023:5561–8.
Ruers T, Van Coevorden F, Punt CJA, Pierie JPEN, Borel-Rinkes I, Ledermann JA, et al. Local treatment of unresectable colorectal liver metastases: results of a randomized phase II trial. JNCI J Natl Cancer Inst. 2017;109(9):djx015.
doi: 10.1093/jnci/djx015
pubmed: 28376151
Treasure T, Farewell V, Macbeth F, Monson K, Williams NR, Brew-Graves C, et al. Pulmonary Metastasectomy versus Continued Active Monitoring in Colorectal Cancer (PulMiCC): a multicentre randomised clinical trial. Trials. 2019;20(1):718.
doi: 10.1186/s13063-019-3837-y
pubmed: 31831062
pmcid: 6909580
Ludmir EB, Sherry AD, Fellman BM, Liu S, Bathala T, Haymaker C, et al. Addition of Metastasis-Directed Therapy to Systemic Therapy for Oligometastatic Pancreatic Ductal Adenocarcinoma (EXTEND): A Multicenter, Randomized Phase II Trial. J Clin Oncol. 2024.
Chmura SJ, Winter KA, Woodward WA, Borges VF, Salama JK, Al-Hallaq HA, et al. NRG-BR002: A phase IIR/III trial of standard of care systemic therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical resection (SR) for newly oligometastatic breast cancer (NCT02364557). J Clin Oncol. 2022;40(16_suppl):1007–1007.
doi: 10.1200/JCO.2022.40.16_suppl.1007
Liu Q, Chen J, Lin Y, Ye J, Shen W, Luo H, et al. Systemic therapy with or without local intervention for oligometastatic oesophageal squamous cell carcinoma (ESO-Shanghai 13): an open-label, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2024;9(1):45–55.
doi: 10.1016/S2468-1253(23)00316-3
pubmed: 37980921
Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, et al. Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: long-term results of the SABR-COMET Phase II Randomized Trial. J Clin Oncol. 2020;38(25):2830–8.
doi: 10.1200/JCO.20.00818
pubmed: 32484754
pmcid: 7460150
Khoo V, Kirby A, Ahmed M, Dewan M, Van As N, Franks K, et al. OC-0761 CORE - Standard of care +/- stereotactic body radiotherapy for oligometastases - primary results. Radiother Oncol. 2023;1(182):S627.
doi: 10.1016/S0167-8140(23)08702-9
Hong JC, Ayala-Peacock DN, Lee J, Blackstock AW, Okunieff P, Sung MW, et al. Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis. PLoS ONE. 2018;13(4):e0195149.
doi: 10.1371/journal.pone.0195149
pubmed: 29649281
pmcid: 5896920
Sahgal A, Myrehaug SD, Siva S, Masucci GL, Maralani PJ, Brundage M, et al. Stereotactic body radiotherapy versus conventional external beam radiotherapy in patients with painful spinal metastases: an open-label, multicentre, randomised, controlled, phase 2/3 trial. Lancet Oncol. 2021;22(7):1023–33.
doi: 10.1016/S1470-2045(21)00196-0
pubmed: 34126044
Gerhard SG, Palma DA, Arifin AJ, Louie AV, Li GJ, Al-Shafa F, et al. Organ at risk dose constraints in SABR: a systematic review of active clinical trials. Pract Radiat Oncol. 2021;11(4):e355–65.
doi: 10.1016/j.prro.2021.03.005
pubmed: 34217495
Nguyen TK, Nguyen EK, Warner A, Louie AV, Palma DA. Failed Randomized clinical trials in radiation oncology: what can we learn? Int J Radiat Oncol Biol Phys. 2018;101(5):1018–24.
doi: 10.1016/j.ijrobp.2018.04.030
pubmed: 29859791
Tsai CJ, Yang JT, Shaverdian N, Patel J, Shepherd AF, Eng J, et al. Standard-of-care systemic therapy with or without stereotactic body radiotherapy in patients with oligoprogressive breast cancer or non-small-cell lung cancer (Consolidative Use of Radiotherapy to Block [CURB] oligoprogression): an open-label, randomised, controlled, phase 2 study. Lancet. 2023;0(0). Available from: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01857-3/fulltext . Cited 2023 Dec 28.
Barnum KJ, Weiss SA. Prognostic and predictive biomarkers in oligometastatic disease. Cancer J Sudbury Mass. 2020;26(2):100–7.
doi: 10.1097/PPO.0000000000000438
Ottaiano A, Santorsola M, Circelli L, Trotta AM, Izzo F, Perri F, et al. Oligo-metastatic cancers: putative biomarkers, emerging challenges and new perspectives. Cancers. 2023;15(6). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047282/ . Cited 2023 Dec 28.