Study Stopped
No participants were enrolled
Re-irradiation With NBTXR3 in Combination With Pembrolizumab for the Treatment of Inoperable Locoregional Recurrent Head and Neck Squamous Cell Cancer
A Phase II Study of Reirradiation With NBTXR3 in Patients With Inoperable Locoregional Recurrent Head and Neck Squamous Cell Carcinoma
2 other identifiers
interventional
N/A
0 countries
N/A
Brief Summary
This phase II trial studies the effect of re-irradiation with NBTXR3 in combination with pembrolizumab in treating patients with head and neck squamous cell cancer that cannot be removed by surgery (inoperable) and has come back (recurrent). NBTXR3 is a drug that is designed to improve the effectiveness (how well something works) of radiation therapy. The drug is injected into a tumor and activated (turned on) by radiation. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Radiation therapy, such as intensity modulated radiation therapy or intensity modulated proton therapy, uses high energy to kill tumor cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving NBTXR3 activated by radiation together with pembrolizumab may help to control head and neck squamous cell cancer.
Trial Health
Trial Health Score
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Started Mar 2021
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 5, 2021
CompletedStudy Start
First participant enrolled
March 9, 2021
CompletedFirst Posted
Study publicly available on registry
April 8, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 21, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
November 21, 2022
CompletedSeptember 13, 2023
September 1, 2023
1.7 years
March 5, 2021
September 11, 2023
Conditions
Outcome Measures
Primary Outcomes (5)
Progression free survival (PFS)
Will be estimated using the method of Kaplan-Meier. Median times and 95% confidence intervals will also be estimated.
From NBTXR3 injection to local or regional recurrence, local or regional progression, distant (outside the head and neck region) progression, or death from any cause, whichever occurs first, assessed up to 5 years
Early clinical benefit activated by SBRT reirradiation
Defined as radiographic evidence of complete response (CR), partial response (PR) or stable disease (SD)
At 6-months post radiation therapy (RT)
Incidence of acute adverse events activated by dose reduction IMRT or IMPT reirradiation
Will assess treatment related acute and late onset toxicities defined as any grade \>= 3 adverse event (AE), excluding dermatitis and mucositis as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
Up to 90 days post RT
Incidence of late adverse events activated by dose reduction IMRT or IMPT reirradiation
Will assess treatment related acute and late onset toxicities defined as any grade \>= 3 AE, excluding dermatitis and mucositis as per NCI CTCAE v 5.0.
From 90 days post RT to end of study (up to 5 years) From 90 days post RT to end of study (up to 5 years)
Incidence of late adverse events activated by SBRT reirradiation
Will assess treatment related acute and late onset toxicities defined as any grade \>= 3 AE, excluding dermatitis and mucositis as per NCI CTCAE v 5.0.
From 90 days post RT to end of study (up to 5 years)
Secondary Outcomes (7)
Objective response rate
Up to 5 years post treatment
Overall response
Up to 5 years post treatment
Incidence of acute adverse events activated by SBRT reirradiation
Up to 90 days post RT
Local PFS
From NBTXR3 injection to the radiographic and/or histological confirmation of local (within 2 cm of the high-dose reirradiation treatment volume [PTV]) disease recurrence, local progression, or death from any cause, assessed up to 5 years
Regional PFS
From NBTXR3 injection to the radiographic and/or histological confirmation of regional disease recurrence, regional progression, or death from any cause, whichever occurs first, assessed up to 5 years
- +2 more secondary outcomes
Other Outcomes (5)
Evaluation of the clinical-grading of lymphedema/fibrosis
Up to 5 years post treatment
Evaluation of the clinical-grading of lymphedema/fibrosis
Up to 5 years post treatment
Evaluation of the clinical-grading of lymphedema/fibrosis
Up to 5 years post treatment
- +2 more other outcomes
Study Arms (2)
Cohort I (NBTXR3, SBRT, pembrolizumab)
EXPERIMENTALPatients receive NBTXR3 IT on day 1. Patients then undergo SBRT QOD on days 15-29. Beginning the first day of radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Cohort II (NBTXR3, IMRT/IMPT, pembrolizumab)
EXPERIMENTALPatients receive NBTXR3 IT on day 1. Patients then undergo IMRT/IMPT QD on days 15-50. Beginning the first day of radiation therapy, patients also receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.
Interventions
Given IT
Undergo IMPT
Undergo IMRT
Given IV
Ancillary studies
Ancillary studies
Undergo SBRT
Eligibility Criteria
You may qualify if:
- Patients with biopsy proven locoregional recurrent squamous cell carcinoma of the head and neck, or second primary HNSCC
- Previous documented receipt of at least 30 Gy and up to 70 Gy of radiation for HNSCC with overlapping fields based on actual dose, prescription percentage
- Gy for conventional fractionation
- Gy for hypofractionation
- Gy for single fraction
- Time interval from prior radiotherapy to NBTXR3 injection (day 1) of at least 6 months
- Not eligible (unresectable) or poor candidate or patient refusal of surgery for HNSCC recurrence
- Amenable to undergo the image guided intratumoral/intranodal injection of NBTXR3 by Interventional Radiologist or ear, nose, and throat (ENT) surgeon, as per investigator or treating physician
- The target lesion(s) in the head and neck should be measurable as per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 on cross sectional imaging and repeated measurements at the same anatomical location should be achievable
- Up to 3 target lesions may be injected with NBTXR3 and radiated, including the primary tumor and involved lymph node(s)
- SBRT cohort: =\< 60 cm\^3 per site, total volume =\< 120 cm\^3
- IMRT/IMPT cohort: =\< 120 cm\^3 per site, total volume =\< 200 cm\^3
- Nodal target lesions must be \>= 15mm (short axis) based on computed tomography (CT) (slice thickness of 5 mm or less) or magnetic resonance imaging (MRI)
- Age \>= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- +11 more criteria
You may not qualify if:
- Locoregional relapse with skin ulceration
- Head and neck carcinoma with radiographic evidence of metastasis at screening
- Surgery to the head and neck
- Excluding diagnostic biopsy
- History of severe immune-related adverse events observed with previous immunotherapy (anti-PD-1/L1) or known sensitivity (grade \>= 3) to any excipients
- Has received any approved or investigational anti-neoplastic agent within 4 weeks prior to NBTXR3 injection
- Except anti-PD-1 therapy, which will not require a washout window
- Note: a reduced washout window may be considered for therapies with short half-lives (i.e., kinase inhibitors) after discussion with Nanobiotix and investigator
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs)
- Replacement therapy (i.e., thyroxine, insulin, or physiologic corticosteroid replacement \[=\< 10 mg prednisone\] therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Has not recovered from adverse events (AEs) due to previous anti-neoplastic or immune-oncology therapy and/or interventions (including radiation) to =\< grade 1
- Participants with alopecia and =\< grade 2 neuropathy may be eligible
- Any live-virus vaccine therapy used for prevention of infectious diseases administered within 4 weeks prior to NBTXR3 injection
- Except killed-virus Influenza vaccine
- Exception of other vaccines (e.g. pneumonia) is at the discretion of the treating physician after conducting a personalized risk assessment on a case by case basis
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jack Phan, MD
M.D. Anderson Cancer Center
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 5, 2021
First Posted
April 8, 2021
Study Start
March 9, 2021
Primary Completion
November 21, 2022
Study Completion
November 21, 2022
Last Updated
September 13, 2023
Record last verified: 2023-09