Clinical trial NCT02379845: NBTXR3 Crystalline Nanoparticles and Radiation Therapy in Treating Randomized Patients in Two Arms With Soft Tissue Sarcoma of the Extremity and Trunk Wall
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Adult Soft Tissue Sarcoma
Lead sponsor: Nanobiotix
Sponsor class: INDUSTRY
Collaborators: name: PharmaEngine
First posted: 2015-03-05
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Pathological Complete Response Rate (pCRR)
timeFrame: 36 months
Secondary outcomes:
measure: Incidence of early and late TEAE, post-TEAE, SAE and laboratory abnormalities (NCI CTCAE V4.0)
timeFrame: 36 months
measure: Objective Response Rate (ORR) by Imaging (MRI) according to RECIST 1.1
timeFrame: 36 months
measure: Tumor volume changes (theoretical tumor volume estimated as: Length x Width x Depth
timeFrame: 36 months
measure: Resection Margins (R0, R1, R2)
timeFrame: 36 months
measure: Hyalinization, fibrosis, necrosis and tumor infarction percentage
timeFrame: 36 months
measure: Limb amputation rate
timeFrame: 36 months
Other outcomes:
measure: Local and distant recurrence rate
timeFrame: 12 months and 24 months
Locations:
city: Canberra
country: Australia
facility: Capital Region Cancer Service, Canberra Hospital
city: Sydney
country: Australia
facility: Chris O'Brien Lifehouse
city: Bruxelles
country: Belgium
facility: Jules Bordet Institute
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Nantes
country: France
facility: Centre Rene Gauducheau
state: Saint Herblain
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre Le Cancer Paul Lamarque
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie
city: Toulouse
country: France
facility: Institut Claudius Regaud - Oncopole
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Mannheim
country: Germany
facility: Klinikum Mannheim
city: Nürnberg
country: Germany
facility: Klinikum Nürnberg
city: Shatin
country: Hong Kong
facility: Princes of Wales Hospital
city: Budapest
country: Hungary
facility: Medical Centre, Hungarian Defence Forces
city: Budapest
country: Hungary
facility: National Institute of Oncology
city: Pecs
country: Hungary
facility: University Pècs
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Padova
country: Italy
facility: Institute of Oncology Veneto IOV
city: Rome
country: Italy
facility: Instituto Nazionale Tumori Regina Elena
city: Oslo
country: Norway
facility: Oslo University Hospital
city: Cebu City
country: Philippines
facility: Perpetual Succour Hospital Cebu
city: Manila
country: Philippines
facility: University of Santo Thomas
city: Pasig City
country: Philippines
facility: The Medical City
city: Quezon City
country: Philippines
facility: St. Luke's Medical Center
city: Warsaw
country: Poland
facility: Cancer Center Institute
city: Bucharest
country: Romania
facility: Institutul Oncologic Bucuresti
city: Bucharest
country: Romania
facility: Spitalului Universitar de Urgenta Militar Central
city: Floresti
country: Romania
facility: Amethyst-Cluj
city: Oradea
country: Romania
facility: County Hospital 'Dr Gavril Curteanu'
city: Targu Mures
country: Romania
facility: County Hospital, Targu Mures
city: Timisoara
country: Romania
facility: Municipal Emergency Hospital
city: Bloemfontein
country: South Africa
facility: Iatros International
city: Durban
country: South Africa
facility: The Oncology Centre
city: George
country: South Africa
facility: Gvi Outeniqua Oncology Unit
city: Pretoria
country: South Africa
facility: Wilgers Oncology Centre
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron
city: Madrid
country: Spain
facility: Hospital Clinico Universitario San Carlos
city: Madrid
country: Spain
facility: START MADRID, Hospital Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: START MADRID, Hospital Universitario Madrid Norte Sanchinarro
Study officials:
References:
citation: Bonvalot S, Rutkowski PL, Thariat J, Carrere S, Ducassou A, Sunyach MP, Agoston P, Hong A, Mervoyer A, Rastrelli M, Moreno V, Li RK, Tiangco B, Herraez AC, Gronchi A, Mangel L, Sy-Ortin T, Hohenberger P, de Baere T, Le Cesne A, Helfre S, Saada-Bouzid E, Borkowska A, Anghel R, Co A, Gebhart M, Kantor G, Montero A, Loong HH, Verges R, Lapeire L, Dema S, Kacso G, Austen L, Moureau-Zabotto L, Servois V, Wardelmann E, Terrier P, Lazar AJ, Bovee JVMG, Le Pechoux C, Papai Z. NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial. Lancet Oncol. 2019 Aug;20(8):1148-1159. doi: 10.1016/S1470-2045(19)30326-2. Epub 2019 Jul 8.