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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Adult Soft Tissue Sarcoma

Intervention / Treatment
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* Device: NBTXR3
* Device: Radiation therapy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>NBTXR3 + Radiotherapy | Device: NBTXR3<br>* One intratumor implantation by injection<br>* Other names: PEP503;Device: Radiation therapy<br>* 5 weeks/50 Gy (5 x 2 Gy by week)<br>|
| Active Comparator: Arm B<br>Radiotherapy alone | Device: Radiation therapy<br>* 5 weeks/50 Gy (5 x 2 Gy by week)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Limb amputation rate |  | 36 months |