Gastrointestinal Cancer

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SU_12_2124 - Hafnium Oxide Nanoparticles Activated By Radiation Therapy: An Innovative Approach for the Treatment of Liver Cancers

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Hafnium Oxide Nanoparticles Activated By Radiation Therapy: An Innovative Approach for the Treatment of Liver Cancers
E. Chajon Rodriguez1, M. Pracht2, T. De Baere3, T. V. F. Nguyen4, J. P. Bronowicki5, V. Vendrely6, A. S. Baumann7, V. V. Croisé-Laurent7, E. Rio8, Y. Rolland9, S. Le Sourd9, P. Gustin3, C. Perret10, F. Mornex11, D. Peiffert12, P. Merle13, and E. Deutsch14; 1Centre Eugène Marquis - Département de Radiothérapie, Rennes, France, 2Centre Eugene Marquis, Rennes, France, 3Institut Gustave Roussy, Villejuif, France, 4Gustave Roussy, Villejuif, France, 5INSERM 954, CHU de Nancy, Université de Lorraine, Nancy, France, 6University Hospital of Bordeaux, Bordeaux, France, 7Institut de Cancérologie de Lorraine, Nancy, France, 8Institut de Cancérologie de l’Ouest, Nantes, France, 9Centre Eugène Marquis, Rennes, France, 10Institut de Cancérologie de l'Ouest, Nantes, France, 11Centre Hospitalier Lyon Sud, Pierre Bénite, France, 12Institut de Cancérologie de Lorraine, Vandoeuvre-Les-Nancy, France, 13Service d'Hepatogastroentérologie, Hôpital de la Croix Rousse, Lyon, France, 14Gustave Roussy, Université Paris-Saclay, Villejuif, France

Purpose/Objective(s): Radiation oncology technological development is principally focused in improving the precision of radiotherapy (RT) to reduce unwanted irradiation to normal tissues. There is an unmet medical need into ameliorating the energy dose deposit within tumor cells without increasing the dose received by surrounding healthy tissues. In response, hafnium oxide nanoparticles, NBTXR3, were developed. Only when activated by RT, NBTXR3 increases the probability of interaction with incoming radiations to enhance the energy dose deposition within tumor cells leading to their death. Their use could be particularly relevant in the management of liver cancers, notably hepatocellular carcinoma (HCC) and liver metastasis (mets). This population is heterogeneous and difficult to treat due to the presence of underlying liver dysfunction and concomitant malignancies. NBTXR3 activated by stereotactic body radiotherapy (SBRT) is currently evaluated in this population in a phase I/II study [NCT02721056]. The multidisciplinary aspect of the study, emphasized by the plurality of liver affections, leads physicians from multiple backgrounds to combine their expertise in managing patient’s course. Herein we present the preliminary results of this study.

Materials/Methods: Eleven patients (pts) with primary HCC (with/without portal vein tumor thrombus) or liver mets were included and treated with a single intralesional (IT) or intraarterial injection of NBTXR3 followed by SBRT (45 Gy / 3 fractions / 5 to 7 weeks). All patients had at least a 3 months follow-up. As SBRT is not supported by all French hospitals, in some cases the coordination of two institutions was needed in managing the patient’s course. The study was designed as a 3 + 3 escalation dose with tested dose levels at 10%, 15%, 22%, 33% and 45% of baseline tumor volume. Primary endpoints include the determination of the recommended dose and of early dose limiting toxicities (DLT). Secondary endpoints include evaluation of NBTXR3 residency and/or presence of leakage and efficacy assessed by mRECIST response.

Results: IT injections were successful and RT was delivered as planned with no early DLT, Adverse Events (AE) nor Serious AE related to NBTXR3 for dose levels of 10% (6 pts), 15% (4 pts) and 22% (1 pt). So far, two AEs (malaise, grade 2; abdominal pain, grade 3) related to the IT injection were reported at the 10% and 15% dose levels. Seven patients were evaluable for tumor response. The overall best response assessed by local assessment were: 3 complete responses, 3 partial responses and 1 stable disease. Importantly, NBTXR3 nanoparticles did not disturb the reliability of image-guided RT.

Conclusion: NBTXR3 was well tolerated and shows a promising safety profile. Recruitment of dose level 22% is ongoing. This study successfully demonstrated the feasibility of a complex multidisciplinary coordination for 2 different important indications in liver oncology.

Author Disclosure: E. Chajon Rodriguez: None. M. Pracht: None. T. De Baere: None. J. Bronowicki: None. A. Baumann: None. V. Croisé-Laurent: None. E. Rio: None. P. Merle: None.

Enrique Chajon Rodriguez, MD, PhD

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