SBRT-LATTICE-PATHY

Official title

Impact of Partial Stereotactic Body Radiotherapy in Hypoxic Segments of Large-volume Unresectable Tumors (SBRT-LATTICE-PATHY) - a Prospective Phase II Study.

Overview

To assess the importance of using SBRT-LATTICE-PATHY for the radiotherapy treatment of large tumors that would be considered intractable by currently used standard techniques. In this present study, the investigators will have the possibility of combining SBRT and LATTICE techniques, incorporating the concept of hypoxic tissue irradiation, which are potential modulators of abscopal and bystander effects, performing partial punctual treatment in the vertex region, without the need for irradiation of the entire tissue volume, further improving safety in relation to possible toxicities.

Interventions

• Radiation SBRT-LATTICE-PATHY
  SBRT-LATTICE-PATHY, a single dose of 24Gy in intratumoral vertices located in hypoxic regions.

Primary outcome measures

• Rate of local control at 12 months [Time frame: From enrollment to the end of treatment at 12 months]
• Tumor volume shrinkage at 12 months [Time frame: From enrollment to the end of treatment at 12 months]

Secondary outcome measures (5)

• 12-month overall survival rate [Time frame: 12 months overall survival]
• 12-month progression-free survival rate [Time frame: 12 months Progression Free Survival]
• Rate of acute adverse events assessed by CTCAE v 5.0 [Time frame: 15 days, 1 month and 3 months after treatment initiation]
• Rate of late adverse events assessed by CTCAE v5.0 [Time frame: 6, 9 and 12 months after treatment completion]
• Mean EORTC QLC-C30 Global Health Status / Quality of Life Score) [Time frame: Impact in quality of life in 1, 3, 6, 9 and 12 months after treatment completion]

Eligibility criteria

Inclusion criteria

• age =or> 18 years;
• Eastern Cooperative Oncology Group (ECOG) performance status < 2; benign and malignant tumors for which the use of radiotherapy is well established in the literature;
• tumors =or> 340 cm³ or with a largest diameter =or> 7 cm;
• no indication for any other type of treatment due to lack of proven clinical benefit (surgery, chemotherapy, standard radiotherapy, immunotherapy, targeted therapy, etc.);
• Palliative Prognostic Index (PPI) =or< 2;
• metastatic disease in the central nervous system (CNS), if present, controlled (up to 3 metastases, each up to 1 cm);
• up to 5 extracranial distant metastases (nodal or extranodal) =or< 5 cm; signed Informed Consent Form (ICF).

Exclusion criteria

• cases in which tumor volume and/or the patient's clinical condition make adequate immobilization/simulation impossible;
• previous local radiotherapy;
• pregnant patients;
• autoimmune diseases;
• genetic instability syndromes;
• ongoing systemic therapy;
• renal insufficiency that prevents the use of iodinated contrast.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Brazil · 1 center

• Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - Instituto de — São Paulo

Publications

• Korpics MC, Onderdonk BE, Dadey RE, Hara JH, Karapetyan L, Zha Y, Karrison TG, Olson AC, Fleming GF, Weichselbaum RR, Bao R, Chmura SJ, Luke JJ. Partial tumor irradiation plus pembrolizumab in treating large advanced solid tumor metastases. J Clin Invest. 2023 May 15;133(10):e162260. doi: 10.1172/JCI162260. PMID 37183819
• Amendola BE, Perez NC, Wu X, Blanco Suarez JM, Lu JJ, Amendola M. Improved outcome of treating locally advanced lung cancer with the use of Lattice Radiotherapy (LRT): A case report. Clin Transl Radiat Oncol. 2018 Jan 12;9:68-71. doi: 10.1016/j.ctro.2018.01.003. eCollection 2018 Feb. PMID 29594253
• Yan W, Khan MK, Wu X, Simone CB 2nd, Fan J, Gressen E, Zhang X, Limoli CL, Bahig H, Tubin S, Mourad WF. Spatially fractionated radiation therapy: History, present and the future. Clin Transl Radiat Oncol. 2019 Oct 22;20:30-38. doi: 10.1016/j.ctro.2019.10.004. eCollection 2020 Jan. No abstract available. PMID 31768424
• Ikeda T, Sun L, Tsuruoka N, Ishigaki Y, Yoshitomi Y, Yoshitake Y, Yonekura H. Hypoxia down-regulates sFlt-1 (sVEGFR-1) expression in human microvascular endothelial cells by a mechanism involving mRNA alternative processing. Biochem J. 2011 Jun 1;436(2):399-407. doi: 10.1042/BJ20101490. PMID 21382012
• Duriseti S, Kavanaugh JA, Szymanski J, Huang Y, Basarabescu F, Chaudhuri A, Henke L, Samson P, Lin A, Robinson C, Spraker MB. LITE SABR M1: A phase I trial of Lattice stereotactic body radiotherapy for large tumors. Radiother Oncol. 2022 Feb;167:317-322. doi: 10.1016/j.radonc.2021.11.023. Epub 2021 Dec 4. PMID 34875286
• Tubin S, Popper HH, Brcic L. Novel stereotactic body radiation therapy (SBRT)-based partial tumor irradiation targeting hypoxic segment of bulky tumors (SBRT-PATHY): improvement of the radiotherapy outcome by exploiting the bystander and abscopal effects. Radiat Oncol. 2019 Jan 29;14(1):21. doi: 10.1186/s13014-019-1227-y. PMID 30696472
• Tubin S, Ahmed MM, Gupta S. Radiation and hypoxia-induced non-targeted effects in normoxic and hypoxic conditions in human lung cancer cells. Int J Radiat Biol. 2018 Mar;94(3):199-211. doi: 10.1080/09553002.2018.1422085. Epub 2018 Jan 12. PMID 29293036

Identifiers

NCT: NCT07645261 · 86859225.3.0000.0068

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗