NBTXR3 Crystalline Nanoparticles and Radiation Therapy in Treating Randomized Patients in Two Arms With Soft Tissue Sarcoma of the Extremity and Trunk Wall

Adult Soft Tissue Sarcoma Clinical Trial

Official title:

A Multicenter Randomized, Open-Label Phase II/III Study, To Compare The Efficacy Of NBTXR3, Implanted As Intratumor Injection And Activated By Radiotherapy, Versus Radiotherapy Alone In Patients With Locally Advanced Soft Tissue Sarcoma Of The Extremity And Trunk Wall

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02379845
• Other study ID #: NBTXR3-301
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 3, 2015
• Est. completion date: September 20, 2020

Study information

• Verified date: April 2021
• Source: Nanobiotix
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy given before surgery of soft tissue sarcoma decreases the size of the tumor mass and the presence of malignant cells in its peripheral region. NBTXR3 and radiation therapy may kill more cancer cells and increase the tumor shrinkage rendering surgery more feasible or easier and achieve better local control of the tumor.

PURPOSE: This phase II/III is a prospective randomized, multi-center, open-label and active controlled two arms study in patients with locally advanced soft tissue sarcoma (STS) of the extremity and trunk wall. Patients will be randomized to receive either NBTXR3 as intratumor injection, activated by external beam radiation therapy or external beam radiation therapy alone, as preoperative treatment. Once the radiotherapy treatment is completed, tumor surgery will be performed in all patients.

Description:

Patients who will be allocated in arm A, will receive a single intratumor injection of NBTXR3 and will receive external beam radiotherapy starting 24hrs after the injection up to completion of 5 weeks, 5 days a week of treatment (50Gy, 2Gy/fraction). Then, all patients will undergo surgical resection of the tumor 5 weeks later and will be followed for wound healing and toxicity assessment. A visit of end of treatment will take place approximately 3-4 weeks after surgery. Patients will be followed for evaluation of their disease status and adverse event until the end of study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: September 20, 2020
• Est. primary completion date: May 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age: 18 years and older

• Locally Advanced Soft Tissue Sarcoma of the Extremity and Trunk Wall

• All grades

• Candidate to radiotherapy + surgery (ESMO guideline 2014) i.e. tumor must not have involvement of bone and / or vessel and or nerve :

• Primary tumor or,

• Relapsed tumor, localized out of previously irradiated area

• WHO performance score 0 to 2

• Adequate function of bone marrow

• Adequate renal function

• Adequate hepatic function

• Adequate pulmonary function

• All female patients of childbearing potential must have a negative serum/urinary pregnancy test

Exclusion Criteria:

• Absence of written Informed Consent duly signed and dated

• Patients with the following histological type: embryonal or alveolar rhabdomyosarcoma, Ewing's sarcoma, osteosarcoma or chondrosarcoma, Kaposi's sarcoma, primitive neuroectodermal tumor, angiosarcoma, aggressive fibromatosis or dermatofibrosarcoma protuberans

• Soft Tissue Sarcoma of the Trunk Wall localized in the abdominal region i.e. the region defined cranially by the xiphoid process of the sternum and the costal margins, and caudally by the line joining the anterior superior iliac spines, both limited by the perpendicular lines crossing both nipples

• Patient with a calculated tumor baseline volume > 3000 mL

• Metastatic disease (CT-scan / MRI verification) with life expectancy shorter than 6 months

• Previous radiation therapy in relapse site of soft tissue sarcoma (no radiation re-challenge is permitted)

• Concurrent treatment with any other anticancer therapy, including chemotherapy, immunotherapy, targeted therapy, gene therapy, or patients planning to receive these treatments during the study

• Absence of histologically or cytologically proven cancer at the first diagnosis

• Previous neoadjuvant chemotherapy treatment given as an upfront of the current treatment line

• Hemolytic anemia

• Autoimmune disease

• Complete initial work up earlier than 4 weeks prior to patient registration

• Patients unable to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

• Patients participating in another clinical investigation at the time of signature of the informed consent

Related Conditions & MeSH terms

• Adult Soft Tissue Sarcoma
• Sarcoma

Intervention

Device:
• NBTXR3
One intratumor implantation by injection
• Radiation therapy
5 weeks/50 Gy (5 x 2 Gy by week)

Locations

Country	Name	City	State
Australia	Capital Region Cancer Service, Canberra Hospital	Canberra
Australia	Chris O'Brien Lifehouse	Sydney
Belgium	Jules Bordet Institute	Bruxelles
Belgium	Ghent University Hospital	Ghent
France	Institut Bergonie	Bordeaux
France	Centre Leon Berard	Lyon
France	Institut Paoli Calmettes	Marseille
France	Centre Regional de Lutte Contre Le Cancer Paul Lamarque	Montpellier
France	Centre Rene Gauducheau	Nantes	Saint Herblain
France	Centre Antoine Lacassagne	Nice
France	Institut Curie	Paris
France	Institut Claudius Regaud - Oncopole	Toulouse
France	Institut Gustave Roussy	Villejuif
Germany	Klinikum Mannheim	Mannheim
Germany	Klinikum Nürnberg	Nürnberg
Hong Kong	Princes of Wales Hospital	Shatin
Hungary	Medical Centre, Hungarian Defence Forces	Budapest
Hungary	National Institute of Oncology	Budapest
Hungary	University Pècs	Pecs
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milan
Italy	Institute of Oncology Veneto IOV	Padova
Italy	Instituto Nazionale Tumori Regina Elena	Rome
Norway	Oslo University Hospital	Oslo
Philippines	Perpetual Succour Hospital Cebu	Cebu City
Philippines	University of Santo Thomas	Manila
Philippines	The Medical City	Pasig City
Philippines	St. Luke's Medical Center	Quezon City
Poland	Cancer Center Institute	Warsaw
Romania	Institutul Oncologic Bucuresti	Bucharest
Romania	Spitalului Universitar de Urgenta Militar Central	Bucharest
Romania	Amethyst-Cluj	Floresti
Romania	County Hospital 'Dr Gavril Curteanu'	Oradea
Romania	County Hospital, Targu Mures	Targu Mures
Romania	Municipal Emergency Hospital	Timisoara
South Africa	Iatros International	Bloemfontein
South Africa	The Oncology Centre	Durban
South Africa	Gvi Outeniqua Oncology Unit	George
South Africa	Wilgers Oncology Centre	Pretoria
Spain	Hospital Universitari Vall D'Hebron	Barcelona
Spain	Hospital Clinico Universitario San Carlos	Madrid
Spain	START MADRID, Hospital Fundacion Jimenez Diaz	Madrid
Spain	START MADRID, Hospital Universitario Madrid Norte Sanchinarro	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
Nanobiotix	PharmaEngine

Countries where clinical trial is conducted

Australia,  Belgium,  France,  Germany,  Hong Kong,  Hungary,  Italy,  Norway,  Philippines,  Poland,  Romania,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Local and distant recurrence rate		12 months and 24 months
Primary	Pathological Complete Response Rate (pCRR)	To compare antitumor activity in terms of Pathological complete response rate (pCRR) of intratumor injection of NBTXR3 activated by external beam radiation therapy (EBRT), versus EBRT alone	36 months
Secondary	Incidence of early and late TEAE, post-TEAE, SAE and laboratory abnormalities (NCI CTCAE V4.0)		36 months
Secondary	Objective Response Rate (ORR) by Imaging (MRI) according to RECIST 1.1		36 months
Secondary	Tumor volume changes (theoretical tumor volume estimated as: Length x Width x Depth		36 months
Secondary	Resection Margins (R0, R1, R2)		36 months
Secondary	Hyalinization, fibrosis, necrosis and tumor infarction percentage		36 months
Secondary	Limb amputation rate		36 months