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

Primary Purpose

Adult Soft Tissue Sarcoma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
NBTXR3
Radiation therapy
Sponsored by
Nanobiotix
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Soft Tissue Sarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Capital Region Cancer Service, Canberra Hospital
  • Chris O'Brien Lifehouse
  • Jules Bordet Institute
  • Ghent University Hospital
  • Centre Rene Gauducheau
  • Institut Bergonie
  • Centre Leon Berard
  • Institut Paoli Calmettes
  • Centre Regional de Lutte Contre Le Cancer Paul Lamarque
  • Centre Antoine Lacassagne
  • Institut Curie
  • Institut Claudius Regaud - Oncopole
  • Institut Gustave Roussy
  • Klinikum Mannheim
  • Klinikum Nürnberg
  • Princes of Wales Hospital
  • Medical Centre, Hungarian Defence Forces
  • National Institute of Oncology
  • University Pècs
  • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Institute of Oncology Veneto IOV
  • Instituto Nazionale Tumori Regina Elena
  • Oslo University Hospital
  • Perpetual Succour Hospital Cebu
  • University of Santo Thomas
  • The Medical City
  • St. Luke's Medical Center
  • Cancer Center Institute
  • Institutul Oncologic Bucuresti
  • Spitalului Universitar de Urgenta Militar Central
  • Amethyst-Cluj
  • County Hospital 'Dr Gavril Curteanu'
  • County Hospital, Targu Mures
  • Municipal Emergency Hospital
  • Iatros International
  • The Oncology Centre
  • Gvi Outeniqua Oncology Unit
  • Wilgers Oncology Centre
  • Hospital Universitari Vall D'Hebron
  • Hospital Clinico Universitario San Carlos
  • START MADRID, Hospital Fundacion Jimenez Diaz
  • START MADRID, Hospital Universitario Madrid Norte Sanchinarro

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A

Arm B

Arm Description

NBTXR3 + Radiotherapy

Radiotherapy alone

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Incidence of early and late TEAE, post-TEAE, SAE and laboratory abnormalities (NCI CTCAE V4.0)
Objective Response Rate (ORR) by Imaging (MRI) according to RECIST 1.1
Tumor volume changes (theoretical tumor volume estimated as: Length x Width x Depth
Resection Margins (R0, R1, R2)
Hyalinization, fibrosis, necrosis and tumor infarction percentage
Limb amputation rate

Full Information

First Posted
February 19, 2015
Last Updated
April 5, 2021
Sponsor
Nanobiotix
Collaborators
PharmaEngine
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1. Study Identification

Unique Protocol Identification Number
NCT02379845
Brief Title
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

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
March 3, 2015 (Actual)
Primary Completion Date
May 22, 2018 (Actual)
Study Completion Date
September 20, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nanobiotix
Collaborators
PharmaEngine

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Soft Tissue Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
180 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm Description
NBTXR3 + Radiotherapy
Arm Title
Arm B
Arm Type
Active Comparator
Arm Description
Radiotherapy alone
Intervention Type
Device
Intervention Name(s)
NBTXR3
Other Intervention Name(s)
PEP503
Intervention Description
One intratumor implantation by injection
Intervention Type
Device
Intervention Name(s)
Radiation therapy
Intervention Description
5 weeks/50 Gy (5 x 2 Gy by week)
Primary Outcome Measure Information:
Title
Pathological Complete Response Rate (pCRR)
Description
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
Time Frame
36 months
Secondary Outcome Measure Information:
Title
Incidence of early and late TEAE, post-TEAE, SAE and laboratory abnormalities (NCI CTCAE V4.0)
Time Frame
36 months
Title
Objective Response Rate (ORR) by Imaging (MRI) according to RECIST 1.1
Time Frame
36 months
Title
Tumor volume changes (theoretical tumor volume estimated as: Length x Width x Depth
Time Frame
36 months
Title
Resection Margins (R0, R1, R2)
Time Frame
36 months
Title
Hyalinization, fibrosis, necrosis and tumor infarction percentage
Time Frame
36 months
Title
Limb amputation rate
Time Frame
36 months
Other Pre-specified Outcome Measures:
Title
Local and distant recurrence rate
Time Frame
12 months and 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Capital Region Cancer Service, Canberra Hospital
City
Canberra
Country
Australia
Facility Name
Chris O'Brien Lifehouse
City
Sydney
Country
Australia
Facility Name
Jules Bordet Institute
City
Bruxelles
Country
Belgium
Facility Name
Ghent University Hospital
City
Ghent
Country
Belgium
Facility Name
Centre Rene Gauducheau
City
Nantes
State/Province
Saint Herblain
Country
France
Facility Name
Institut Bergonie
City
Bordeaux
Country
France
Facility Name
Centre Leon Berard
City
Lyon
Country
France
Facility Name
Institut Paoli Calmettes
City
Marseille
Country
France
Facility Name
Centre Regional de Lutte Contre Le Cancer Paul Lamarque
City
Montpellier
Country
France
Facility Name
Centre Antoine Lacassagne
City
Nice
Country
France
Facility Name
Institut Curie
City
Paris
Country
France
Facility Name
Institut Claudius Regaud - Oncopole
City
Toulouse
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
Country
France
Facility Name
Klinikum Mannheim
City
Mannheim
Country
Germany
Facility Name
Klinikum Nürnberg
City
Nürnberg
Country
Germany
Facility Name
Princes of Wales Hospital
City
Shatin
Country
Hong Kong
Facility Name
Medical Centre, Hungarian Defence Forces
City
Budapest
Country
Hungary
Facility Name
National Institute of Oncology
City
Budapest
Country
Hungary
Facility Name
University Pècs
City
Pecs
Country
Hungary
Facility Name
Fondazione IRCCS Istituto Nazionale dei Tumori
City
Milan
Country
Italy
Facility Name
Institute of Oncology Veneto IOV
City
Padova
Country
Italy
Facility Name
Instituto Nazionale Tumori Regina Elena
City
Rome
Country
Italy
Facility Name
Oslo University Hospital
City
Oslo
Country
Norway
Facility Name
Perpetual Succour Hospital Cebu
City
Cebu City
Country
Philippines
Facility Name
University of Santo Thomas
City
Manila
Country
Philippines
Facility Name
The Medical City
City
Pasig City
Country
Philippines
Facility Name
St. Luke's Medical Center
City
Quezon City
Country
Philippines
Facility Name
Cancer Center Institute
City
Warsaw
Country
Poland
Facility Name
Institutul Oncologic Bucuresti
City
Bucharest
Country
Romania
Facility Name
Spitalului Universitar de Urgenta Militar Central
City
Bucharest
Country
Romania
Facility Name
Amethyst-Cluj
City
Floresti
Country
Romania
Facility Name
County Hospital 'Dr Gavril Curteanu'
City
Oradea
Country
Romania
Facility Name
County Hospital, Targu Mures
City
Targu Mures
Country
Romania
Facility Name
Municipal Emergency Hospital
City
Timisoara
Country
Romania
Facility Name
Iatros International
City
Bloemfontein
Country
South Africa
Facility Name
The Oncology Centre
City
Durban
Country
South Africa
Facility Name
Gvi Outeniqua Oncology Unit
City
George
Country
South Africa
Facility Name
Wilgers Oncology Centre
City
Pretoria
Country
South Africa
Facility Name
Hospital Universitari Vall D'Hebron
City
Barcelona
Country
Spain
Facility Name
Hospital Clinico Universitario San Carlos
City
Madrid
Country
Spain
Facility Name
START MADRID, Hospital Fundacion Jimenez Diaz
City
Madrid
Country
Spain
Facility Name
START MADRID, Hospital Universitario Madrid Norte Sanchinarro
City
Madrid
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
31296491
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. Erratum In: Lancet Oncol. 2019 Sep;20(9):e468.
Results Reference
derived

Learn more about this trial

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

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