Back to resultsNBTXR3 and Radiation Therapy in Treating Patients With Locally Advanced SCC of the Oral Cavity or Oropharynx
Primary Purpose
Head and Neck Cancer
Status
Active
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
NBTXR3 activated by IMRT
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Cancer focused on measuring Oral cavity Cancer, Oropharynx Cancer
Eligibility Criteria
Inclusion criteria:
- Patients aged ≥ 70 years old, or
- Patients aged ≥ 65 years old and < 70 years old who are unable to receive cisplatin, or
- Patients who have contraindication to cisplatin or that are intolerant to cisplatin or cetuximab or that cannot receive the combination of chemoradiation, regardless the age
- 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 AJCC guidelines (8th Edition, 2018)
- No evidence of distant metastatic disease, as determined by a negative PET scan or CT scan
- Clinically eligible for intratumor implantation by injection
- Karnofsky Performance Status ≥ 70
Adequate function of Bone marrow:
- White Blood Cell (WBC) > 3.0 x 10^9/L
- Absolute neutrophil count (ANC) > or = 1.0 x 10^9/L
- Platelet count > or = 100 x 10^9/L
- Hemoglobin > or = 9.0 g/dL
Adequate function of Kidney:
o Creatinine < or = 3.0 x ULN or creatinine clearance > or = 30 mL/min/1.73m²
Adequate function of the liver:
- AST < or = 5 x ULN
- ALT < or = 5 x ULN
- Bilirubin < or = 1.5 x ULN
- Negative pregnancy test ≤ 7 days of NBTXR3 injection in all females of child-bearing potential
Exclusion Criteria:
- Written Informed Consent not obtained, signed and dated
- 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 RECIST criteria
- History of stroke, 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.
Sites / Locations
- Centre Francois Baclesse
- Centre Oscar Lambret
- Hôpital La Timone
- Centre Antoine Lacassagne
- Institut Curie
- CHU Pontchaillou
- Institut de Cancérologie de la Loire Lucien Neuwirth
- Institut Gustave Roussy
- Hungarian Defense Forces Hospital
- National Institute of Oncology
- Centrum Onkologii - Instytut im. M. Skłodowskiej- Curie, Oddział w Gliwicach
- Świętokrzyskie Centrum Onkologii Samodzielny Publiczny Zakład Opieki Zdrowotnej W Kielcach
- Centrum Onkologii Ziemi Lubelskiej im. Św. Jana z Dukli
- NU-MED, Provita Prolife
- Nu-Med Centrum Diagnostyki I Terapii Onkologicznej Zamość Spółka Z Ograniczoną Odpowiedzialnością
- Institut Catala d'Oncologia Hospital
- Vall d'Hebron Hospital
- Hospital Fundación Jimenez Diaz
- Hospital Universitario Madrid Sanchinarro
- Hospital Universitario Regional de Malaga
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
NBTXR3 IntraTumoral injection (IT)
Arm Description
Single intratumor injection
Outcomes
Primary Outcome Measures
Dose Escalation: Incidence of DLTs and determination of the Recommended Phase 2 Dose
The incidence of early DLTs (early adverse effects related to NBTXR3, as an intratumor injection, activated by IMRT)
Dose Escalation: Determination of the Recommended Phase 2 Dose
The recommended Phase II dose (RD) of NBTXR3 administered as intratumor injection, activated by Intensity Modulated Radiation Therapy (IMRT)
Dose Expansion: Overall Response Rate
The Objective Response Rate (ORR) of the primary tumor, by imaging according to RECIST 1.1
Dose Expansion: Complete Response Rate
The Complete Response Rate (CRR) of the primary tumor, by imaging according to RECIST 1.1
Secondary Outcome Measures
Dose Escalation: Objective Response Rate (ORR) of the primary tumor
The Objective Response Rate (ORR) of the primary tumor, by imaging according to RECIST 1.1
Dose Escalation: Complete Response Rate
The Complete Response Rate (CRR) of the primary tumor, by imaging according to RECIST 1.1
Dose Expansion: Local Progression Free Survival
Local Progression Free Survival (LPFS) defined as any recurrence at the site of the primary tumor
Dose Expansion: Progression Free Survival
Progression Free Survival (PFS) defined as the time to any progression at the site of the primary tumor, in regional lymph nodes and/or distant metastasis
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01946867
Brief Title
NBTXR3 and Radiation Therapy in Treating Patients With Locally Advanced SCC of the Oral Cavity or Oropharynx
Official Title
A Phase I Dose-Escalation/Dose Expansion Study Of NBTXR3 Activated By Intensity Modulated Radiation Therapy In Patients With Locally Advanced Squamous Cell Carcinoma Of The Oral Cavity Or Oropharynx
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 3, 2014 (Actual)
Primary Completion Date
February 2023 (Anticipated)
Study Completion Date
February 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nanobiotix
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
Detailed Description
Patients will receive a single administration of NBTXR3 on day 1,as an 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
Keywords
Oral cavity Cancer, Oropharynx Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
This study consists of two parts: Dose Escalation and Dose Expansion. This phase I is an open-label non-randomized, dose-escalation/dose expansion study of safety and tolerability evaluation of NBTXR3, administered as an intratumoral implantation by injection, activated by intensity modulated radiation therapy (IMRT), in patients with locally advanced squamous cell carcinoma of the oral cavity or oropharynx.
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NBTXR3 IntraTumoral injection (IT)
Arm Type
Experimental
Arm Description
Single intratumor injection
Intervention Type
Device
Intervention Name(s)
NBTXR3 activated by IMRT
Primary Outcome Measure Information:
Title
Dose Escalation: Incidence of DLTs and determination of the Recommended Phase 2 Dose
Description
The incidence of early DLTs (early adverse effects related to NBTXR3, as an intratumor injection, activated by IMRT)
Time Frame
12 months
Title
Dose Escalation: Determination of the Recommended Phase 2 Dose
Description
The recommended Phase II dose (RD) of NBTXR3 administered as intratumor injection, activated by Intensity Modulated Radiation Therapy (IMRT)
Time Frame
12 months
Title
Dose Expansion: Overall Response Rate
Description
The Objective Response Rate (ORR) of the primary tumor, by imaging according to RECIST 1.1
Time Frame
12-24 months
Title
Dose Expansion: Complete Response Rate
Description
The Complete Response Rate (CRR) of the primary tumor, by imaging according to RECIST 1.1
Time Frame
12-24 months
Secondary Outcome Measure Information:
Title
Dose Escalation: Objective Response Rate (ORR) of the primary tumor
Description
The Objective Response Rate (ORR) of the primary tumor, by imaging according to RECIST 1.1
Time Frame
12-24 months
Title
Dose Escalation: Complete Response Rate
Description
The Complete Response Rate (CRR) of the primary tumor, by imaging according to RECIST 1.1
Time Frame
12 months
Title
Dose Expansion: Local Progression Free Survival
Description
Local Progression Free Survival (LPFS) defined as any recurrence at the site of the primary tumor
Time Frame
12-24 months
Title
Dose Expansion: Progression Free Survival
Description
Progression Free Survival (PFS) defined as the time to any progression at the site of the primary tumor, in regional lymph nodes and/or distant metastasis
Time Frame
12-24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Patients aged ≥ 70 years old, or
Patients aged ≥ 65 years old and < 70 years old who are unable to receive cisplatin, or
Patients who have contraindication to cisplatin or that are intolerant to cisplatin or cetuximab or that cannot receive the combination of chemoradiation, regardless the age
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 AJCC guidelines (8th Edition, 2018)
No evidence of distant metastatic disease, as determined by a negative PET scan or CT scan
Clinically eligible for intratumor implantation by injection
Karnofsky Performance Status ≥ 70
Adequate function of Bone marrow:
White Blood Cell (WBC) > 3.0 x 10^9/L
Absolute neutrophil count (ANC) > or = 1.0 x 10^9/L
Platelet count > or = 100 x 10^9/L
Hemoglobin > or = 9.0 g/dL
Adequate function of Kidney:
o Creatinine < or = 3.0 x ULN or creatinine clearance > or = 30 mL/min/1.73m²
Adequate function of the liver:
AST < or = 5 x ULN
ALT < or = 5 x ULN
Bilirubin < or = 1.5 x ULN
Negative pregnancy test ≤ 7 days of NBTXR3 injection in all females of child-bearing potential
Exclusion Criteria:
Written Informed Consent not obtained, signed and dated
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 RECIST criteria
History of stroke, 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christophe LE TOURNEAU, MD-PhD
Organizational Affiliation
Institut Curie Paris France
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre Francois Baclesse
City
Caen
ZIP/Postal Code
14076
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59000
Country
France
Facility Name
Hôpital La Timone
City
Marseille
ZIP/Postal Code
13385
Country
France
Facility Name
Centre Antoine Lacassagne
City
Nice
ZIP/Postal Code
06189
Country
France
Facility Name
Institut Curie
City
Paris
ZIP/Postal Code
75005
Country
France
Facility Name
CHU Pontchaillou
City
Rennes
ZIP/Postal Code
35033
Country
France
Facility Name
Institut de Cancérologie de la Loire Lucien Neuwirth
City
Saint-Priest-en-Jarez
ZIP/Postal Code
42270
Country
France
Facility Name
Institut Gustave Roussy
City
Villejuif
ZIP/Postal Code
94800
Country
France
Facility Name
Hungarian Defense Forces Hospital
City
Budapest
Country
Hungary
Facility Name
National Institute of Oncology
City
Budapest
Country
Hungary
Facility Name
Centrum Onkologii - Instytut im. M. Skłodowskiej- Curie, Oddział w Gliwicach
City
Gliwice
Country
Poland
Facility Name
Świętokrzyskie Centrum Onkologii Samodzielny Publiczny Zakład Opieki Zdrowotnej W Kielcach
City
Kielce
Country
Poland
Facility Name
Centrum Onkologii Ziemi Lubelskiej im. Św. Jana z Dukli
City
Lublin
Country
Poland
Facility Name
NU-MED, Provita Prolife
City
Tomaszów Mazowiecki
Country
Poland
Facility Name
Nu-Med Centrum Diagnostyki I Terapii Onkologicznej Zamość Spółka Z Ograniczoną Odpowiedzialnością
City
Zamość
Country
Poland
Facility Name
Institut Catala d'Oncologia Hospital
City
Barcelona
Country
Spain
Facility Name
Vall d'Hebron Hospital
City
Barcelona
Country
Spain
Facility Name
Hospital Fundación Jimenez Diaz
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Madrid Sanchinarro
City
Madrid
Country
Spain
Facility Name
Hospital Universitario Regional de Malaga
City
Málaga
ZIP/Postal Code
29010
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
33607477
Citation
Hoffmann C, Calugaru V, Borcoman E, Moreno V, Calvo E, Liem X, Salas S, Doger B, Jouffroy T, Mirabel X, Rodriguez J, Chilles A, Bernois K, Dimitriu M, Fakhry N, Hee Kam SW, Le Tourneau C. Phase I dose-escalation study of NBTXR3 activated by intensity-modulated radiation therapy in elderly patients with locally advanced squamous cell carcinoma of the oral cavity or oropharynx. Eur J Cancer. 2021 Mar;146:135-144. doi: 10.1016/j.ejca.2021.01.007. Epub 2021 Feb 16.
Results Reference
derived
Learn more about this trial
NBTXR3 and Radiation Therapy in Treating Patients With Locally Advanced SCC of the Oral Cavity or Oropharynx
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