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

NCT ID: NCT02379845

Last Updated: 2021-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-03
• Study Completion Date: 2020-09-20

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.

Conditions

Adult Soft Tissue Sarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

NBTXR3 + Radiotherapy

Group Type: EXPERIMENTAL

NBTXR3

Intervention Type: DEVICE

One intratumor implantation by injection

Radiation therapy

Intervention Type: DEVICE

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

Arm B

Radiotherapy alone

Group Type: ACTIVE_COMPARATOR

Radiation therapy

Intervention Type: DEVICE

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

Interventions

NBTXR3

One intratumor implantation by injection

Intervention Type: DEVICE

Radiation therapy

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

Intervention Type: DEVICE

Other Intervention Names

PEP503

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmaEngine

INDUSTRY

Sponsor Role: collaborator

Nanobiotix

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Capital Region Cancer Service, Canberra Hospital

Canberra, , Australia

Chris O'Brien Lifehouse

Sydney, , Australia

Jules Bordet Institute

Brussels, , Belgium

Ghent University Hospital

Ghent, , Belgium

Centre Rene Gauducheau

Nantes, Saint Herblain, 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 Antoine Lacassagne

Nice, , France

Institut Curie

Paris, , France

Institut Claudius Regaud - Oncopole

Toulouse, , France

Institut Gustave Roussy

Villejuif, , France

Klinikum Mannheim

Mannheim, , Germany

Klinikum Nürnberg

Nuremberg, , Germany

Princes of Wales Hospital

Shatin, , Hong Kong

Medical Centre, Hungarian Defence Forces

Budapest, , Hungary

National Institute of Oncology

Budapest, , Hungary

University Pècs

Pécs, , Hungary

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Institute of Oncology Veneto IOV

Padua, , Italy

Instituto Nazionale Tumori Regina Elena

Rome, , Italy

Oslo University Hospital

Oslo, , Norway

Perpetual Succour Hospital Cebu

Cebu City, , Philippines

University of Santo Thomas

Manila, , Philippines

The Medical City

Pasig, , Philippines

St. Luke's Medical Center

Quezon City, , Philippines

Cancer Center Institute

Warsaw, , Poland

Institutul Oncologic Bucuresti

Bucharest, , Romania

Spitalului Universitar de Urgenta Militar Central

Bucharest, , Romania

Amethyst-Cluj

Floreşti, , Romania

County Hospital 'Dr Gavril Curteanu'

Oradea, , Romania

County Hospital, Targu Mures

Târgu Mureş, , Romania

Municipal Emergency Hospital

Timișoara, , Romania

Iatros International

Bloemfontein, , South Africa

The Oncology Centre

Durban, , South Africa

Gvi Outeniqua Oncology Unit

George, , South Africa

Wilgers Oncology Centre

Pretoria, , South Africa

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, , Spain

Countries

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

References

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.

Reference Type: DERIVED

PMID: 31296491 (View on PubMed)

Other Identifiers

NBTXR3-301

Identifier Type: -

Identifier Source: org_study_id