Clinical trial NCT01433068: NBTXR3 Crystalline Nanoparticles and Radiation Therapy in Treating Patients With Soft Tissue Sarcoma of the Extremity
Official title: An Open-Label, Single Arm, Feasibility And Safety Phase I Study With NBTXR3 Intratumor Implantation (By Injection) And Activated By External Beam Radiation Therapy In Patients With Soft Tissue Sarcoma Of The Extremity And Trunk Wall
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Adult Soft Tissue Sarcoma
Keywords: Adult Soft Tissue Sarcoma of the extremities and Trunk wall
Lead sponsor: Nanobiotix
Sponsor class: INDUSTRY
First posted: 2011-09-13
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 I trial aims at evaluating the feasibility of the NBTXR3 injection in the tumor, safety and the adequate dose of NBTXR3 when given with radiation therapy.

Detailed description: Patients will receive a single intratumor injection of NBTXR3 on day 1 and will receive external beam radiotherapy starting on day 2 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 events every 8 weeks until the end of study.

Eligibility criteria: Inclusion Criteria:

* Age: 18 years and older
* Soft tissue sarcoma of the extremity or trunk wall, or localized in the posterior region of the neck (i.e., coronal section passing through the posterior limit of the ear)
* Locally advanced soft tissue sarcoma,candidate to radiotherapy

  * Primary tumor or,
  * Relapsed tumor, localized out of already irradiated area or,
  * Sarcomas secondary to previous irradiation exposure due to other primary cancer
* WHO performance score 0 to 2
* Adequate function of Bone marrow:
* Adequate renal function
* Adequate liver function
* All female patients of childbearing potential must have a negative serum/urinary pregnancy test

Exclusion Criteria:

* Written Informed Consent not obtained, signed and dated
* Patients with the following histological type: Gastrointestinal Stromal Tumors (GIST), embryonal or alveolar rhabdomyosarcoma, Ewing's sarcoma, osteosarcoma or chondrosarcoma, Kaposi's sarcoma, primitive neuroectodermal tumor 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
* Angiosarcoma of the trunk wall because of its diffuse frontier
* Metastatic disease (CT-scan verification) with survival expectation \< 6 months
* Concurrent treatment with any other anticancer therapy
* Absence of histologically or cytologically proven cancer at the first diagnosis
* Previous neoadjuvant chemotherapy treatment given as an upfront of the current treatment line
* Previous radiation therapy in relapse site of the soft tissue sarcoma (no radiation re-challenge is permitted)
* Moderate and severe liver dysfunction
* 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.

Primary outcomes:
measure: Evaluation of the feasibility of the intratumor injection of NBTXR3
timeFrame: 6 months
measure: Assessment of the safety profile and determination of early dose limiting toxicity
timeFrame: 20 months
Secondary outcomes:
measure: Evaluation of the anti-tumor activity of NBTXR3 in terms of pathological Response (pR)
timeFrame: 20 months
measure: Evaluation of the Response Rate (RR) of NBTXR3 as per RECIST
timeFrame: 20 months
measure: Characterization of the body kinetic profile of NBTXR3
timeFrame: 20 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Institut Bergonie
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Head of Surgery Division
name: Sylvie BONVALOT, MD-PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Head of Radiotherapy Department
name: Guy KANTOR, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References: