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

NCT02379845 | Completed Phase 2 DMC

• 1 other identifier: NBTXR3-301
• Study Type: interventional
• Target: 180
• Locations: 13 countries
• Sites: 42

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.

Conditions

Adult Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Incidence of early and late TEAE, post-TEAE, SAE and laboratory abnormalities (NCI CTCAE V4.0)

  36 months

• Objective Response Rate (ORR) by Imaging (MRI) according to RECIST 1.1

  36 months

• Tumor volume changes (theoretical tumor volume estimated as: Length x Width x Depth

  36 months

• Resection Margins (R0, R1, R2)

  36 months

• Hyalinization, fibrosis, necrosis and tumor infarction percentage

  36 months

Other Outcomes (1)

• Local and distant recurrence rate

  12 months and 24 months

Study Arms (2)

Arm A

EXPERIMENTAL

NBTXR3 + Radiotherapy

Device: NBTXR3; Device: Radiation therapy

Arm B

ACTIVE COMPARATOR

Radiotherapy alone

Device: Radiation therapy

Interventions

NBTXR3 DEVICE

One intratumor implantation by injection

Also known as: PEP503

Arm A

Radiation therapy DEVICE

5 weeks/50 Gy (5 x 2 Gy by week)

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nanobiotix: lead
• PharmaEngine: collaborator

Study Sites (42)

Capital Region Cancer Service, Canberra Hospital

Canberra, Australia

Location

Chris O'Brien Lifehouse

Sydney, Australia

Location

Jules Bordet Institute

Brussels, Belgium

Location

Ghent University Hospital

Ghent, Belgium

Location

Centre Rene Gauducheau

Nantes, Saint Herblain, France

Location

Institut Bergonie

Bordeaux, France

Location

Centre Leon Berard

Lyon, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Centre Regional de Lutte Contre Le Cancer Paul Lamarque

Montpellier, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Institut Curie

Paris, France

Location

Institut Claudius Regaud - Oncopole

Toulouse, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Klinikum Mannheim

Mannheim, Germany

Location

Klinikum Nürnberg

Nuremberg, Germany

Location

Princes of Wales Hospital

Shatin, Hong Kong

Location

Medical Centre, Hungarian Defence Forces

Budapest, Hungary

Location

National Institute of Oncology

Budapest, Hungary

Location

University Pècs

Pécs, Hungary

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

Institute of Oncology Veneto IOV

Padua, Italy

Location

Instituto Nazionale Tumori Regina Elena

Rome, Italy

Location

Oslo University Hospital

Oslo, Norway

Location

Perpetual Succour Hospital Cebu

Cebu City, Philippines

Location

University of Santo Thomas

Manila, Philippines

Location

The Medical City

Pasig, Philippines

Location

St. Luke's Medical Center

Quezon City, Philippines

Location

Cancer Center Institute

Warsaw, Poland

Location

Institutul Oncologic Bucuresti

Bucharest, Romania

Location

Spitalului Universitar de Urgenta Militar Central

Bucharest, Romania

Location

Amethyst-Cluj

Floreşti, Romania

Location

County Hospital 'Dr Gavril Curteanu'

Oradea, Romania

Location

County Hospital, Targu Mures

Târgu Mureş, Romania

Location

Municipal Emergency Hospital

Timișoara, Romania

Location

Iatros International

Bloemfontein, South Africa

Location

The Oncology Centre

Durban, South Africa

Location

Gvi Outeniqua Oncology Unit

George, South Africa

Location

Wilgers Oncology Centre

Pretoria, South Africa

Location

Hospital Universitari Vall D'Hebron

Barcelona, Spain

Location

Hospital Clinico Universitario San Carlos

Madrid, Spain

Location

START MADRID, Hospital Fundacion Jimenez Diaz

Madrid, Spain

Location

START MADRID, Hospital Universitario Madrid Norte Sanchinarro

Madrid, Spain

Location

Related Publications (1)

• 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.

  PMID: 31296491 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2015
• First Posted: March 5, 2015
• Study Start: March 3, 2015
• Primary Completion: May 22, 2018
• Study Completion: September 20, 2020
• Last Updated: April 6, 2021

Record last verified: 2021-04

Locations

RO (6); AU (2); BE (2); DE (2); PL (1); IT (3); HU (3); ES (4); HK (1); FR (9); PH (4); NO (1); ZA (4)