{"id":2631,"date":"2022-05-26T08:41:21","date_gmt":"2022-05-26T07:41:21","guid":{"rendered":"https:\/\/bibliography.nanobiotix.com\/?p=2631"},"modified":"2022-05-26T10:22:00","modified_gmt":"2022-05-26T09:22:00","slug":"2019-phase-i-ii-trial-of-nbtxr3-activated-by-sbrt-in-patients-with-hepatocellular-carcinoma-or-liver-metastasis","status":"publish","type":"post","link":"https:\/\/bibliography.nanobiotix.com\/fr\/2019-phase-i-ii-trial-of-nbtxr3-activated-by-sbrt-in-patients-with-hepatocellular-carcinoma-or-liver-metastasis\/","title":{"rendered":"2019 \u2013 Phase I\/II trial of NBTXR3 activated by SBRT in patients with hepatocellular carcinoma or liver metastasis"},"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]M. Pracht1<\/span>, E. Chajon2<\/span>, Y. Rolland3<\/span>, T. de Baere4<\/span>, F. Nguyen4<\/span>, J-P. Bronowicki5<\/span>, V. Vendrely6<\/span>, A. Sa Cunha7<\/span>, A-S. Baumann8<\/span>, V. Croise\u00b4 -Laurent5<\/span>, E. Rio9<\/span>, P. Said10<\/span>, S. Le Sourd11<\/span>, P. Gustin12<\/span>, C. Perret9<\/span>, D. Peiffert8<\/span>, E. Deutsch13<\/span>
\n
\n1 \u2014 Medical Oncology Department, Centre Eugene – Marquis, Rennes, France
\n2 \u2014 Department of Radiotherapy, Centre Eugene – Marquis, Rennes, France
\n3 \u2014 Radiology Department, Centre Eugene – Marquis, Rennes, France
\n4 \u2014 Interventional Radiology, Institut Gustave Roussy, Villejuif, France
\n5 \u2014 Hepatology and Gastroenterology, CHU Brabois, Vandoeuvre Les Nancy, France
\n6 \u2014 Radiotherapy, CHU Bordeaux, Pessac, France
\n7 \u2014 Centre Hepetobiliaire, Universit\u00e9 Paris Sud, Orsay, France
\n8 \u2014 Radiation Oncology, Unicancer – Cancer Institute of Lorraine, Nancy, France
\n9 \u2014 Radiotherapy, Institut de Cancerologie de l\u2019Ouest, Nantes, France
\n10 \u2014 Biometry, Nanobiotix SA, Paris, France
\n11 \u2014 Medical Oncology Department, Centre Eugene – Marquis, Rennes, France
\n12 \u2014 Breast Cancer Services, Institut Gustave Roussy, Villejuif, France
\n13 \u2014 Radiotherapy, Institut Gustave Roussy, Villejuif, France
\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″]Background:<\/b> Treatment of hepatocellular carcinoma (HCC) and liver metastasis (mets) is challenging due to presence of underlying disease, e.g. cirrhosis. Stereotactic body radiation therapy (SBRT) is a well-tolerated alternative for inoperable patients (pts), yet maximal dose to the tumor is limited by potential toxicity to surrounding healthy tissues. Otherwise inert, NBTXR3 (hafnium oxide nanoparticles) when activated by ionizing radiation (RT) augments dose deposit within tumor cells, increasing tumor cell death compared to RT alone.
\nA phase I\/II clinical trial is underway to evaluate NBTXR3 activated by SBRT in pts with HCC or liver mets [NCT02721056].<\/p>\n

Methods:<\/b> A 3+3 dose escalation was utilized in the phase I. Pts received a single intralesional injection (ILI) of NBTXR3 followed by SBRT (45 Gy\/3 fractions\/5-7 days), with tested NBTXR3 dose levels of 10, 15, 22 and 33% of baseline tumor volume. Primary endpoints included recommended phase II dose(s) identification and DLT. Secondary endpoints included global safety profile assessment, liver function by Child-Pugh score (CPS), AST to Platelet Ratio Index (APRI), and response rate (mRECIST\/RECIST v1.1).<\/p>\n

Results:<\/b> Four dose escalation levels are finalized (n=17): 6 pts at 10% (2 SBRT doses tested due to organ constraints), 4 pts at 15 and 22% (due to fiducial displacement and ILI site shift) and 3 pts at 33%. No NBTXR3 related DLTs were observed. Related AEs observed: one malaise (G2, 10%); 2 abdominal pain, (G3, 15%); one bilateral pleural effusion (G1, 22%), one bile duct stenosis (G3, 22%) with associated disease recurrence and SBRT; one fatigue (G1, 33%). There were no clinically meaningful changes to CPS or APRI and CT-scan demonstrated absence of NBTXR3 in surrounding healthy tissues. In 7 evaluable HCC pts, best mRECIST target lesion responses were: 3 CR, 4 PR. In 5 evaluable mets pts, best target lesion responses were: 2 PR, 1 SD, 2 PD.<\/p>\n

Conclusions:<\/b> NBTXR3 was well tolerated and showed preliminary anti-tumor activity, supporting a protocol amendment to evaluate an additional NBTXR3 dose level (42%). This innovative approach has the potential to address an unmet medical need in pts with unresectable primary or metastatic liver lesions.[\/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":"

Treatment of hepatocellular carcinoma (HCC) and liver metastasis (mets) is challenging due to presence of underlying disease, e.g. cirrhosis. Stereotactic body radiation therapy (SBRT) is a well-tolerated alternative for inoperable patients (pts), yet maximal dose to the tumor is limited by potential toxicity to surrounding healthy tissues. [\u2026]<\/p>\n","protected":false},"author":1,"featured_media":2636,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[182,183,669],"tags":[349,193,528,455,463,200],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/2631"}],"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=2631"}],"version-history":[{"count":1,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/2631\/revisions"}],"predecessor-version":[{"id":2637,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/2631\/revisions\/2637"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/media\/2636"}],"wp:attachment":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/media?parent=2631"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/categories?post=2631"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/tags?post=2631"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}