OSNA Versus Ultrastaging to Detect Sentinel Lymph Node Metastasis in Endometrial Cancer

Official title

One Step Nucleic Acid Amplification (OSNA) Versus Ultrastaging to Detect Sentinel Lymph Node Metastasis in Endometrial Cancer: a Randomized, Multicenter, Controlled Trial (SENT-OSNA Study)

Overview

Patients enrolled in the study will be randomized before surgery: in one study arm, the search for lymph node metastases in surgically removed sentinel lymph nodes will occur using the ultrastaging method (standard), while in the other arm it will be conducted using the OSNA method.

Detailed description

This is a non-inferiority randomized trial with the incidence of patients with metastatic SLN as primary endpoint. Based on recent literature, incidence of patients with metastatic SLN detected by ultrastaging has an average value of 11%. Assuming a -4% as the maximum allowable difference in detection rate to declare non-inferiority, a power of 80% and a significance level of 2.5% (one-side) a sample size of 1922 (961 per arm) is needed. Two interim analyses are planned, one after the first 640 and the second after 1280 patients. At the first interim analysis null hypothesis (inferiority of OSNA with respect to ultrastaging) will be rejected at a significance level \<0.00010 otherwise the study will go on and at the second analysis the null hypothesis will be rejected at a significance level of 0.0059. The final analysis will use 0.0189 as significance threshold. The O'Brien Fleming alpha spending function was used to define these values.

The primary endpoint is defined as the proportion of patients with positive SLN over the total of randomized patients. This proportion will be reported together with the 95% confidence interval to better identify the range of inferential values. Incidence of isolated tumor cells, micro- and macro-metastasis will be calculated.

Number of copies of CK19 mRNA to define volume of metastases will be adapted from previous reports.

To describe the sample, quantitative variables will be summarized using median and interquartile range while categorical items will be reported as absolute counts and percentages. Patients will be described according the arm they were randomized to. A first analysis will be performed on an Intent-To-Treat basis, considering all randomized patients. A secondary analysis will be performed on the Per-Protocol population.

Interventions

• Device OSNA
  The search for lymph node metastases in surgically removed sentinel lymph nodes will occur using the OSNA method
• Device Ultrastaging
  The search for lymph node metastases in surgically removed sentinel lymph nodes will occur using the ultrastaging method

Primary outcome measures

• Number of SLN metastasis detected by OSNA versus ultrastaging method [Time frame: From enrollment to the acquisition of the histological examination (8 weeks)]

Secondary outcome measures (9)

• Overall survival (measured in months) in patients with a diagnosis of lymph node metastases (identified with OSNA and ultrastaging), performing stratification by molecular class. [Time frame: 3 years (a 3-year follow-up is planned)]
• Disease-free survival (measured in months) in patients with a diagnosis of lymph node metastases (identified with OSNA and ultrastaging), performing stratification by molecular class. [Time frame: 3 years (a 3-year follow-up is planned)]
• 3 year disease-free survival (measured in months) in OSNA versus ultrastaging negative patients [Time frame: 3 years (a 3-year follow-up is planned)]
• 3 year overall survival (measured in months) in OSNA versus ultrastaging negative patients [Time frame: 3 years (a 3-year follow-up is planned)]
• 5-year disease-free survival (measured in months) in OSNA versus ultrastaging negative patients [Time frame: 5 years]
• 5-year overall survival (measured in months) in OSNA versus ultrastaging negative patients [Time frame: 5 years]
• Incidence of endosalpingiosis in ultrastaging arm [Time frame: From enrollment to the acquisition of the histological examination (8 weeks)]
• Total Tumor Load (calculating by summing the number of copies of CK19 from each sentinel lymph node) and correlation with prognosis [Time frame: 3 years (a 3-year follow-up is planned)]
• Dimension of SLN (measured in millimeters) metastases at ultrastaging and correlation with prognosis [Time frame: 3 years (a 3-year follow-up is planned)]

Eligibility criteria

Inclusion criteria

• Histologically confirmed endometrial cancer
• Apparent (pre-operative) FIGO stage I-II
• Radical surgery
• Attempt of SLN mapping

Exclusion criteria

• Uterine sarcoma (including endometrial stromal sarcoma)
• Fertility sparing surgery
• Dedifferentiated histology
• Undifferentiated histology
• Neoadjuvant therapy
• Previous surgery to pelvic lymph nodes
• Lymph nodes with short axis >15 mm at pre-operative imaging

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

Italy · 1 center

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Rome

Publications

• Marchocki Z, Cusimano MC, Clarfield L, Kim SR, Fazelzad R, Espin-Garcia O, Bouchard-Fortier G, Rossi EC, Stewart KI, Soliman PT, How JA, Gotlieb WH, Holloway RW, Ianieri MM, Cabrera S, Lim YK, Ferguson SE. Sentinel lymph node biopsy in high-grade endometrial cancer: a systematic review and meta-analysis of performance characteristics. Am J Obstet Gynecol. 2021 Oct;225(4):367.e1-367.e39. doi: 10.10 PMID 34058168
• Persson J, Salehi S, Bollino M, Lonnerfors C, Falconer H, Geppert B. Pelvic Sentinel lymph node detection in High-Risk Endometrial Cancer (SHREC-trial)-the final step towards a paradigm shift in surgical staging. Eur J Cancer. 2019 Jul;116:77-85. doi: 10.1016/j.ejca.2019.04.025. Epub 2019 Jun 7. PMID 31181536
• Koh WJ, Abu-Rustum NR, Bean S, Bradley K, Campos SM, Cho KR, Chon HS, Chu C, Cohn D, Crispens MA, Damast S, Dorigo O, Eifel PJ, Fisher CM, Frederick P, Gaffney DK, George S, Han E, Higgins S, Huh WK, Lurain JR 3rd, Mariani A, Mutch D, Nagel C, Nekhlyudov L, Fader AN, Remmenga SW, Reynolds RK, Tillmanns T, Ueda S, Wyse E, Yashar CM, McMillian NR, Scavone JL. Uterine Neoplasms, Version 1.2018, NCCN PMID 29439178
• Bodurtha Smith AJ, Fader AN, Tanner EJ. Sentinel lymph node assessment in endometrial cancer: a systematic review and meta-analysis. Am J Obstet Gynecol. 2017 May;216(5):459-476.e10. doi: 10.1016/j.ajog.2016.11.1033. Epub 2016 Nov 18. PMID 27871836
• Bogani G, Murgia F, Ditto A, Raspagliesi F. Sentinel node mapping vs. lymphadenectomy in endometrial cancer: A systematic review and meta-analysis. Gynecol Oncol. 2019 Jun;153(3):676-683. doi: 10.1016/j.ygyno.2019.03.254. Epub 2019 Apr 2. PMID 30952370
• Concin N, Matias-Guiu X, Vergote I, Cibula D, Mirza MR, Marnitz S, Ledermann J, Bosse T, Chargari C, Fagotti A, Fotopoulou C, Gonzalez Martin A, Lax S, Lorusso D, Marth C, Morice P, Nout RA, O'Donnell D, Querleu D, Raspollini MR, Sehouli J, Sturdza A, Taylor A, Westermann A, Wimberger P, Colombo N, Planchamp F, Creutzberg CL. ESGO/ESTRO/ESP guidelines for the management of patients with endometria PMID 33397713
• Lortet-Tieulent J, Ferlay J, Bray F, Jemal A. International Patterns and Trends in Endometrial Cancer Incidence, 1978-2013. J Natl Cancer Inst. 2018 Apr 1;110(4):354-361. doi: 10.1093/jnci/djx214. PMID 29045681
• Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021 Jan;71(1):7-33. doi: 10.3322/caac.21654. Epub 2021 Jan 12. PMID 33433946

Identifiers

NCT: NCT06935305 · 7170

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗