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

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ClinicalTrials.gov Identifier: NCT02379845
Recruitment Status : Active, not recruiting
First Posted : March 5, 2015
Last Update Posted : June 4, 2018
Sponsor:
Collaborator:
PharmaEngine
Information provided by (Responsible Party):
Nanobiotix

Tracking Information
First Submitted Date  ICMJE February 19, 2015
First Posted Date  ICMJE March 5, 2015
Last Update Posted Date June 4, 2018
Study Start Date  ICMJE February 2015
Estimated Primary Completion Date June 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 1, 2015)
Pathological Complete Response Rate (pCRR) [ Time Frame: 36 months ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02379845 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2018)
  • Incidence of early and late TEAE, post-TEAE, SAE and laboratory abnormalities (NCI CTCAE V4.0) [ Time Frame: 36 months ]
  • Objective Response Rate (ORR) by Imaging (MRI) according to RECIST 1.1 [ Time Frame: 36 months ]
  • Tumor volume changes (theoretical tumor volume estimated as: Lenght x Width x Depth [ Time Frame: 36 months ]
  • Resection Margins (R0, R1, R2) [ Time Frame: 36 months ]
  • Limb amputation rate [ Time Frame: 36 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 1, 2015)
  • Incidence of early and late TEAE, post-TEAE, SAE and laboratory abnormalities (NCI CTCAE V4.0) [ Time Frame: 30 months ]
  • Objective Response Rate (ORR) by Imaging (MRI) according to RECIST 1.1 [ Time Frame: 30 months ]
  • Tumor volume changes (theoretical tumor volume estimated as: Lenght x Width x Depth [ Time Frame: 30 months ]
  • Resection Margins (R0, R1, R2) [ Time Frame: 30 months ]
  • Limb amputation rate [ Time Frame: 36 months ]
Current Other Pre-specified Outcome Measures
 (submitted: June 1, 2018)
Local and distant recurrence rate [ Time Frame: 12 months and 24 months ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE NBTXR3 Crystalline Nanoparticles and Radiation Therapy in Treating and Randomized Patients in Two Arms With Soft Tissue Sarcoma of the Extremity and Trunk Wall
Official Title  ICMJE MULTICENTER RANDOMIZED, OPEN-LABEL PHASE II/III STUDY, TO COMPARE EFFICACY OF NBTXR3 IMPLANTED AS INTRATUMOR INJECTION AND ACTIVATED BY RADIOTHERAPY, VERSUS RADIOTHERAPY ALONE IN PATIENTS WITH LOCALLY ADVANCED SOFT TISSUE SARCOMA (EXTREMITY AND TRUNK WALL)
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Adult Soft Tissue Sarcoma
Intervention  ICMJE
  • Device: NBTXR3
    One intratumor implantation by injection
    Other Name: PEP503
  • Device: Radiation therapy
    5 weeks/50 Gy (5 x 2 Gy by week)
Study Arms  ICMJE
  • Experimental: Arm A
    NBTXR3 + Radiotherapy
    Interventions:
    • Device: NBTXR3
    • Device: Radiation therapy
  • Active Comparator: Arm B
    Radiotherapy alone
    Intervention: Device: Radiation therapy
Publications * Bonvalot S, Rutkowski PL, Thariat J, Carrère 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 Baère T, Le Cesne A, Helfre S, Saada-Bouzid E, Borkowska A, Anghel R, Co A, Gebhart M, Kantor G, Montero A, Loong HH, Vergés R, Lapeire L, Dema S, Kacso G, Austen L, Moureau-Zabotto L, Servois V, Wardelmann E, Terrier P, Lazar AJ, Bovée JVMG, Le Péchoux 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 Jul 8. pii: S1470-2045(19)30326-2. doi: 10.1016/S1470-2045(19)30326-2. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 1, 2015)
180
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2020
Estimated Primary Completion Date June 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 expextancy shorter than 6 months
  • Previous radiation therapy in relapse site of soft tissue sarcoma (no radiation re-chanllenge 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 visites, treatment plans, laboratory tests, and other study procedures
  • Patients participating in another clinical investigation at the time of signature of the informed consent
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   France,   Germany,   Hong Kong,   Hungary,   Italy,   Norway,   Philippines,   Poland,   Romania,   South Africa,   Spain
Removed Location Countries Canada,   Netherlands
 
Administrative Information
NCT Number  ICMJE NCT02379845
Other Study ID Numbers  ICMJE NBTXR3-301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nanobiotix
Study Sponsor  ICMJE Nanobiotix
Collaborators  ICMJE PharmaEngine
Investigators  ICMJE Not Provided
PRS Account Nanobiotix
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP