{"id":2024,"date":"2019-11-28T12:57:33","date_gmt":"2019-11-28T12:57:33","guid":{"rendered":"https:\/\/bibliography.nanobiotix.com\/?p=2024"},"modified":"2022-05-24T16:59:36","modified_gmt":"2022-05-24T15:59:36","slug":"2019-ctos-nbtxr3-in-sts-phase-ii-iii-trial","status":"publish","type":"post","link":"https:\/\/bibliography.nanobiotix.com\/fr\/2019-ctos-nbtxr3-in-sts-phase-ii-iii-trial\/","title":{"rendered":"2019 CTOS NBTXR3 in STS phase II\/III trial"},"content":{"rendered":"

[vc_row padding_top=\u00a0\u00bb0″ padding_bottom=\u00a0\u00bb0″ section_container_layout=\u00a0\u00bbfull-width\u00a0\u00bb remove_horizontal_padding=\u00a0\u00bbyes\u00a0\u00bb module_type=\u00a0\u00bbbg-color\u00a0\u00bb gutter_size=\u00a0\u00bbyes\u00a0\u00bb equal_height=\u00a0\u00bbyes\u00a0\u00bb bg_color=\u00a0\u00bb#28282e\u00a0\u00bb][vc_column][vc_row_inner padding_top=\u00a0\u00bb0″ padding_bottom=\u00a0\u00bb0″ gutter_size=\u00a0\u00bbyes\u00a0\u00bb equal_height=\u00a0\u00bbyes\u00a0\u00bb][vc_column_inner column_paddings=\u00a0\u00bb105″ column_position_vertical=\u00a0\u00bbmiddle\u00a0\u00bb column_min_height=\u00a0\u00bb700″ column_min_height_sm=\u00a0\u00bb400″ column_min_height_xs=\u00a0\u00bb350″ module_type=\u00a0\u00bbbg-image\u00a0\u00bb bg_image=\u00a0\u00bb99″ mask_fx=\u00a0\u00bbyes-mask\u00a0\u00bb mask_color_mode=\u00a0\u00bbpalette\u00a0\u00bb mask_bg_color_palette=\u00a0\u00bbmain-mask\u00a0\u00bb animation_fx=\u00a0\u00bbyes-animation\u00a0\u00bb animation_delay=\u00a0\u00bb200″ animation_offset_scroll_down=\u00a0\u00bb90″ width=\u00a0\u00bb1\/2″ animation_in=\u00a0\u00bbfadeInUp\u00a0\u00bb][vc_empty_space height=\u00a0\u00bb60px\u00a0\u00bb responsive_lg=\u00a0\u00bbhidden\u00a0\u00bb responsive_md=\u00a0\u00bbhidden\u00a0\u00bb][az_box_icons box_icon_title=\u00a0\u00bbAuthors\u00a0\u00bb box_icon_color_mode=\u00a0\u00bbon-the-fly\u00a0\u00bb icon_visibility=\u00a0\u00bbyes-icon\u00a0\u00bb icon_type=\u00a0\u00bbfont\u00a0\u00bb icon=\u00a0\u00bbfa fa-edit\u00a0\u00bb icon_color_mode=\u00a0\u00bbon-the-fly\u00a0\u00bb icon_size=\u00a0\u00bb50″ box_icon_color=\u00a0\u00bb#ffffff\u00a0\u00bb icon_color=\u00a0\u00bb#ffffff\u00a0\u00bb]Sylvie Bonvalot1<\/span>, Piotr Rutkowski2<\/span>, Juliette Thariat3<\/span>, S\u00e9bastien Carr\u00e8re4<\/span>, Anne Ducassou5<\/span>, Marie-Pierre Sunyach6<\/span>, Peter Agoston7<\/span>, Angela Hong8<\/span>, Augustin Mervoyer9<\/span>, Marco Rastrelli10<\/span>, Victor Moreno11<\/span>, Rubi Li12<\/span>, B\u00e9atrice Tiangco13<\/span>, Vincent Servois1<\/span>, Patricia Sa\u00efd14<\/span>, Mikaela Dimitriu14<\/span>, Eva Wardelmann15<\/span>, Philippe Terrier16<\/span>, Alexander Lazar17<\/span>, Judith Bovee18<\/span>, C\u00e9cile Le P\u00e9choux16<\/span>, Zsusanna Papai19<\/span>
\n
\n1 \u2013 Institut Curie, Paris, France
\n2 \u2013 Maria Sklodowska-Curie Institute -Oncology Center, Warsaw, Poland
\n3 \u2013 Centre Fran\u00e7ois Baclesse, Caen, France
\n4 \u2013 Centre Regional De Lutte Contre Le Cancer Paul Lamarque, Montpellier, France
\n5 \u2013 Institut Universitaire du Cancer de Toulouse-Oncopole (IUCT-O), Toulouse, France; 6L\u00e9on B\u00e9rard Cancer Center, Lyon, France
\n7 \u2013 Orsz\u00e1gos Onkologiai Int\u00e9zet, Budapest, Hungary
\n8 \u2013 The University of Sydney, Camperdown, New South Wales, Australia
\n9 \u2013 Institut de Cancerologie de l\u2019Ouest- Rene Gauducheau, Saint-Herblain, France
\n10 \u2013 Istituto Oncologico Veneto IRCCS, Padua, Italy
\n11 \u2013 Hospital Fundaci\u00f3n Jimenez Diaz, Madrid, Spain
\n12 \u2013 St. Luke\u2019s Medical Center, Quezon City, Philippines
\n13 \u2013 The Medical City APS Cancer Institute, Pasig City, Philippines
\n14 \u2013 Nanobiotix, SA, Paris, France
\n15 \u2013 University Hospital M\u00fcnster, M\u00fcnster, Germany
\n16 \u2013 Institute Gustave Roussy, Villejuif, France
\n17 \u2013 MD Anderson Cancer Center, Houston, TX, USA
\n18 \u2013 Leiden University Medical Center, Leiden, Netherlands
\n19 \u2013 Hungarian Defence Forces, Budapest, Hungary
\n<\/span>[\/az_box_icons][vc_empty_space height=\u00a0\u00bb60px\u00a0\u00bb responsive_lg=\u00a0\u00bbhidden\u00a0\u00bb responsive_md=\u00a0\u00bbhidden\u00a0\u00bb][\/vc_column_inner][vc_column_inner column_paddings=\u00a0\u00bb105″ column_position_vertical=\u00a0\u00bbmiddle\u00a0\u00bb module_type=\u00a0\u00bbbg-color\u00a0\u00bb animation_fx=\u00a0\u00bbyes-animation\u00a0\u00bb animation_delay=\u00a0\u00bb300″ animation_offset_scroll_down=\u00a0\u00bb90″ width=\u00a0\u00bb1\/2″ bg_color=\u00a0\u00bb#ffffff\u00a0\u00bb animation_in=\u00a0\u00bbfadeInUp\u00a0\u00bb][vc_empty_space height=\u00a0\u00bb60px\u00a0\u00bb responsive_lg=\u00a0\u00bbhidden\u00a0\u00bb responsive_md=\u00a0\u00bbhidden\u00a0\u00bb][az_box_icons box_icon_title=\u00a0\u00bbSummary\u00a0\u00bb icon_visibility=\u00a0\u00bbyes-icon\u00a0\u00bb icon_type=\u00a0\u00bbfont\u00a0\u00bb icon=\u00a0\u00bbaz-icon az-icon-layers2″ icon_color_mode=\u00a0\u00bbon-the-fly\u00a0\u00bb icon_color=\u00a0\u00bb#28282e\u00a0\u00bb icon_size=\u00a0\u00bb50″]Objectives:<\/strong>\u00a0A subset of locally advanced soft tissue sarcoma (STS) patients achieve significant therapeutic benefit from preoperative radiation therapy (RT) as shown by Pisters JCO 1996 and Yang JCO 2018. However, the impact of RT on pathological response (pR) and R0 resection is limited, highlighting the need for novel multimodal therapies aimed at local control. NBTXR3 (hafnium oxide nanoparticles), injected intratumorally may represent such an option. Otherwise inert, NBTXR3 augments the effective RT dose deposited within tumor cells when activated by ionizing radiation to increase cancer cell death compared to RT alone.\u00a0We report here on the results of a phase II\/III randomized clinical trial evaluating the preoperative efficacy and safety of NBTXR3 activated by RT in patients with locally advanced STS of the extremity and trunk wall [NCT02379845].<\/p>\n

Methods:<\/strong>\u00a0This is a multi-national phase II\/III randomized, open-label clinical trial. Adults with locally advanced STS of the extremity or trunk wall, of any histologic grade, eligible for preoperative RT were randomly assigned 1:1 to receive NBTXR3 as a single intratumoral injection (volume corresponding to 10% of baseline tumor volume at 53.3g\/L) followed by external beam RT (EBRT; 50 Gy as 25 fractions of 2 Gy, over 5 weeks) (arm A) or EBRT alone (arm B). Both arms had the chance to go on to receive post-RT surgical resection. The primary objective was to compare the proportion of patients with pathological complete response (pCR; defined as <5% of residual viable cancer cells after surgery), as assessed by a Central Pathology Review Board based on the EORTC guidelines. Key secondary endpoints included negative surgical margin (R0), limb amputation rate and safety. Safety was evaluated in all subjects who received at least one puncture of NBTXR3 or at least one fraction of RT. Subjects are in continued long-term follow-up, focused on safety.<\/p>\n

Results:<\/strong>\u00a0Between March 3rd, 2015 and November 21st, 2017, 180 patients were randomized and 179 received treatment: n=89; arm A and n=90; arm B. The proportion of patients with pCR was 16.1% (14\/87) compared with 7.9% (7\/89) in arms A and B, respectively (p=0.044). The R0 resection rate was 77.0% (67\/87) in arm A versus 64.0% (57\/89) in arm B (p=0.0424). The most common grade 3-4 treatment emergent adverse event (AE) was post-operative wound complication, which occurred at a similar rate in each arm (8\/89 and 8\/90 in arm A and B, respectively). The most common grade 3-4 AE related to NBTXR3 administration was injection site pain (4\/89, 4.5%) and hypotension (4\/90, 4.4%). Skin injury was the most common grade 3-4 RT-related AE, which was shared between both arms (5\/89, 5.6% and 4\/90, 4.4% in arm A and B, respectively). Serious AEs were observed in 35 (39.3%) of 89 patients in arm A and 27 (30.0%) of 90 patients in arm B. There were no treatment-related deaths. Follow-up was conducted on 153 patients with a current median follow-up of 18.5 months. Currently 87 patients are still in long-term follow-up.<\/p>\n

Conclusion:<\/strong>\u00a0This registration trial of NBTXR3 combined with EBRT significantly achieved its primary and secondary endpoints of improving pCR, and increasing R0 resection versus EBRT alone. NBTXR3 together with EBRT was well tolerated with a safety profile consistent with EBRT alone. Taken together, these results led to the EU approval (CE Mark) of NBTXR3 + RT for patients with locally advanced STS of the extremity and trunk wall.[\/az_box_icons][vc_empty_space height=\u00a0\u00bb60px\u00a0\u00bb responsive_lg=\u00a0\u00bbhidden\u00a0\u00bb responsive_md=\u00a0\u00bbhidden\u00a0\u00bb][\/vc_column_inner][\/vc_row_inner][\/vc_column][\/vc_row]<\/p>\n<\/section>","protected":false},"excerpt":{"rendered":"

A subset of locally advanced soft tissue sarcoma (STS) patients achieve significant therapeutic benefit from preoperative radiation therapy (RT) as shown by Pisters JCO 1996 and Yang JCO 2018. However, the impact of RT on pathological response (pR) and R0 resection is limited, highlighting the need for novel multimodal therapies aimed at local control. NBTXR3 (hafnium oxide nanoparticles), injected intratumorally may represent such an option. Otherwise inert, NBTXR3 augments the effective RT dose deposited within tumor cells when activated by ionizing radiation to increase cancer cell death compared to RT alone. [\u2026]<\/p>\n","protected":false},"author":1,"featured_media":2031,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[182,183,674],"tags":[548,576,482,577,196,439,342,379,200,566,567,513,318],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/2024"}],"collection":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/comments?post=2024"}],"version-history":[{"count":1,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/2024\/revisions"}],"predecessor-version":[{"id":2033,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/2024\/revisions\/2033"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/media\/2031"}],"wp:attachment":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/media?parent=2024"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/categories?post=2024"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/tags?post=2024"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}