NBTXR3 Crystalline Nanoparticles and Radiation Therapy in Treating Patients With Locally Advanced Squamous Cell Carcinoma of the Oral Cavity or Oropharynx

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Nanobiotix
Sponsor:
Information provided by (Responsible Party):
Nanobiotix
ClinicalTrials.gov Identifier:
NCT01946867
First received: September 10, 2013
Last updated: September 17, 2013
Last verified: August 2013
  Purpose

RATIONALE: Cancers of the oral cavity represent 30% of head and neck carcinomas in the western world. The oropharynx is the posterior continuation of the oral cavity and connects with the nasopharynx (above) and laryngopharynx (below). It is also a frequent site of primary head and neck cancers. These structures play a crucial role in swallowing, breath and speech. Locally advanced oropharyngeal cancers can obstruct the air flow or infiltrate muscles or nerves, which significantly disturb local functions. The incidence of Head and Neck Squamous Cell Cancer in patients older 65 years is high, 47% occurred in this population as recorded by the Surveillance, Epidemiology, and End Results registries in the United States. Regarding the therapeutic strategies, the association of radiotherapy with chemotherapy or biologics has demonstrated significant improvement of outcomes with the drawback of higher toxicity, or as demonstrated by 2 meta-analyses, without survival improvement in older patients. NBTXR3 and radiation therapy may increase the cancer cell killing and complete tumor shrinkage allowing a definitive treatment and preservation of local structures and functions in patients older 65 years, who cannot receive cisplatin.


Condition Intervention Phase
Head and Neck Cancer
Device: NBTXR3
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PhI Study of NBTXR3 With Intensity Modulated Radiation Therapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Oral Cavity or Oropharynx

Resource links provided by NLM:


Further study details as provided by Nanobiotix:

Primary Outcome Measures:
  • Determination of the Recommended Doses and the early Dose Limiting Toxicities (DLT) [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    To determine the Recommended Doses and the early Dose Limiting Toxicities (DLT) of NBTXR3 administered as two different schedules (intra-arterial or intratumor injection), activated by Intensity Modulated Radiation Therapy (IMRT)


Secondary Outcome Measures:
  • Evaluation of the safety and tolerability of NBTXR3 [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Safety and tolerability of NBTXR3, as an intra-arterial or intratumor injection schedule, activated by Intensity Modulated Radiation Therapy (IMRT) will be assessed in terms of incidence and severity of clinical and laboratory Adverse Events.

  • Evaluation of the Objective Response Rate (ORR) and the complete Response Rate as per Response Evaluation Criteria in Solid Tumors (RECIST) and the Tumor Volume estimation [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    To evaluate the Objective Response Rate (ORR) and the complete Response Rate by Magnetic Resonance Imaging (MRI) using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) and the Tumor Volume estimation (Lenght×Width×Depth) of NBTXR3, as an intra-arterial or intratumor injection schedule, activated by Intensity Modulated Radiation Therapy (IMRT)

  • Evaluation of the Local Progression Free Survival (LPFS) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    To evaluate the local Progression Free Survival (lPFS) of NBTXR3, as an intra-arterial or intratumor injection schedule, activated by Intensity Modulated Radiation Therapy (IMRT)

  • Evaluation of the Progression Free Survival (PFS) of NBTXR3 [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    To evaluate the Progression Free Survival (PFS) of NBTXR3, as an intra-arterial or intratumor injection schedule, activated by Intensity Modulated Radiation Therapy (IMRT)

  • Characterization of the body kinetics profile of NBTXR3 [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    To characterize the body kinetics on Day 1 and 2, of NBTXR3 administered by intratumor or intra-arterial injection before its activation by Intensity Modulated Radiation Therapy (IMRT)

  • Evaluation of the feasibility of local administration either intratumor or intra-arterial route [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    The feasibility of local administration, either intratumor or intra-arterial slow injection of NBTXR3, then activated by Intensity Modulated Radiation Therapy (IMRT) will be assessed by duration of injection, number of punctures, and in terms of the NBTXR3 nanoparticles intratumor dispersion.


Estimated Enrollment: 48
Study Start Date: August 2013
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NBTXR3 IntraTumoral injection (IT)
Single intratumor injection
Device: NBTXR3
Experimental: NBTXR3 Intra-Arterial Injection (IA)
Single intra-arterial injection
Device: NBTXR3

Detailed Description:

Patients will receive a single administration of NBTXR3 on day 1, either as an intra-arterial or intratumor injection, followed by Intensity Modulated Radiation Therapy starting 24 hours later (day 2), and up to completion of 7 weeks, i.e. 70 Grays, 2Grays/fraction. Patients whose tumor has completely shrunk will be followed for the post-radiotherapy evaluation up to the End of Treatment visit. Those patients whose tumor has not shrunk more than 50% of the baseline size, will stop the radiotherapy and may have a salvage tumor surgery. Then, all patients will be followed every 8 weeks, for the safety evaluation and cancer disease status until the end of the study.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged ≥ 70 years old
  • Patients aged ≥ 65 years old and < 70 years old with contra-indication to cisplatin
  • Histologically or cytologically confirmed Squamous Cell Carcinoma (SCC) of the oral cavity or oropharynx
  • T3 or T4 primary tumor or Stage III or IVA according to American Joint Committee on Cancer guidelines (AJCC, 7th Edition, 2010)
  • No evidence of distant metastatic disease, as determined by a negative Positron Emission Tomography (PET Scan) or Computerized Tomography (CT Scan)
  • Clinically eligible for either intra-arterial or intratumor implantation by injection
  • KPS Karnofsky performance status) ≥ 70
  • Adequate function of Bone marrow:

    • White Blood Cell (WBC) > 3.0 x 109/l
    • Absolute neutrophil count (ANC) >= 1.0 x 109/l
    • Platelet count >= 100 x 109/l
    • Hemoglobin >= 9.0 g/dL
  • Adequate function of Kidney:

    • Creatinine <= 1.5 x ULN or creatinine clearance >= 50 mL/min/1.73m²
  • Adequate function of liver:

    • AST (Aspartate aminotransferase) <= 5 x ULN
    • ALT (Alanine aminotransferase) <= 5 x ULN
    • Bilirubin <= 1.5 x ULN

Exclusion Criteria:

  • Written Informed Consent not obtained, signed and dated
  • Confirmed patient inoperability
  • Prior radiotherapy to any area within the planned radiotherapy field
  • Tumor-related dyspnea
  • Tumor ulceration which implies vascular risk
  • Non measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
  • History of stroke, Coronary Artery Bypass Graft (CABG), or significant blockage of carotid arteries or coronary arteries or current blockage of coronary or carotid arteries equal to or in excess of 50% blockage
  • Uncontrolled intercurrent illness including, but not limited to,ongoing or active severe infection, symptomatic congestive heart failure, acute coronary syndrome, etc.
  • Medical history of life-threatening ventricular arrhythmia
  • Prior or concurrent non-head and neck malignancies, excluding adequately treated basal or squamous cell cancer of the skin, and in situ cervical cancer, and any other cancer from which the subject has been cancer free for 5 years
  • Concurrent treatment with any other anticancer therapy, including chemotherapy, immunotherapy, targeted therapy, gene therapy, or patients planning to receive these treatments during the study
  • Patients unable to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures or those with severe psychiatric illness/social situations that would limit compliance with study requirements
  • Patients participating in another clinical investigation at the time of signature of the informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01946867

Contacts
Contact: Mikaela Dimitriu, PhD +33 (0)1 40 26 44 44 mikaela.dimitriu@nanobiotix.com
Contact: Elsa BORGHI, MD +33 (0)1 40 26 26 87 elsa.borghi@nanobiotix.com

Locations
France
Institut Curie Recruiting
Paris, France, 75005
Contact: Christophe LE TOURNEAU, MD-PhD         
Contact: José RODRIGUEZ, MD         
Principal Investigator: Christophe LE TOURNEAU, MD-PhD         
Sub-Investigator: José RODRIGUEZ, MD         
Sub-Investigator: Valentin CALUGARU, MD-PhD         
Sponsors and Collaborators
Nanobiotix
Investigators
Principal Investigator: Christophe LE TOURNEAU, MD-PhD Medical Oncology Department
  More Information

No publications provided

Responsible Party: Nanobiotix
ClinicalTrials.gov Identifier: NCT01946867     History of Changes
Other Study ID Numbers: NBTXR3-102, ID RCB: 2013-A00706-39
Study First Received: September 10, 2013
Last Updated: September 17, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Nanobiotix:
Oral cavity Cancer
Oropharynx Cancer

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell

ClinicalTrials.gov processed this record on October 23, 2014