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Recurrent Head and Neck Squamous Cell CarcinomaPhase 2NCT04834349

Re-irradiation With NBTXR3 in Combination With Pembrolizumab for the Treatment of Inoperable Locoregional Recurrent Head and Neck Squamous Cell Cancer

A Phase 2 study testing Hafnium Oxide-containing Nanoparticles NBTXR3, Intensity-Modulated Proton Therapy and Intensity-Modulated Radiation Therapy in people with Recurrent Head and Neck Squamous Cell Carcinoma and Unresectable Head and Neck Squamous Cell Carcinoma, run by M.D. Anderson Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Hafnium Oxide-containing Nanoparticles NBTXR3, Intensity-Modulated Proton Therapy and Intensity-Modulated Radiation Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
9 Mar 2021to 21 Nov 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • 30 Gy for conventional fractionation
  • 15 Gy for hypofractionation
  • 10 Gy for single fraction
  • Time interval from prior radiotherapy to NBTXR3 injection (day 1) of at least 6 months
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  • 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
  • Hemoglobin >= 9.0 g/dL
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Leukocytes >= 1500/mm^3
  • Creatinine =< 1.5 x upper limit of normal (ULN)
  • Calculated (Calc.) creatinine clearance > 30 mL/min
  • Total bilirubin =< 1.5 mg/dL
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN)
  • Serum albumin > 3.5 g/L
  • Negative urine or serum pregnancy test =< 7 days prior to NBTXR3 injection in all women of child-bearing potential (WOCBP). WOCBP must agree to follow instructions for method(s) of contraception for the duration the entire study period and 6 months after the last dose of pembrolizumab treatment. Local laws and regulations may require use of alternative and/or additional contraception methods. WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements but should still undergo pregnancy testing
  • Signed informed consent form (ICF) indicating that participant understands the purpose of, and procedures required for, the study and is willing to participate in the study

Who cannot join

  • 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
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  • 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
  • Prior allogenic stem cell transplantation or organ allograft
  • Known contraindication to iodine-based or gadolinium-based IV contrast
  • Active malignancy, in addition to head and neck carcinoma, with the exception of basal cell carcinoma of the skin definitively treated and relapse free within at least 1 year since diagnosis or low risk prostate cancer
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, renal failure, cardiac arrhythmia, or psychiatric illness that would limit compliance with treatment
  • Known active, uncontrolled (high viral load) human immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
  • Female patients who are pregnant or breastfeeding
  • Women of child-bearing potential and their male partners who are unwilling or unable to use an acceptable method of birth control to avoid pregnancy for the entire study period and up to 6 months, for females, and 220 days for males after the last dose of pembrolizumab
  • Acceptable methods of contraception are those that, alone or in combination, result in a failure rate of < 1% per year when used consistently and correctly
  • Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments

About this study

Official title: A Phase II Study of Reirradiation With NBTXR3 in Patients With Inoperable Locoregional Recurrent Head and Neck Squamous Cell Carcinoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate progression free survival (PFS) and early clinical benefit in patients treated with hafnium oxide-containing nanoparticles NBTXR3 (NBTXR3) activated by stereotactic body radiation therapy (SBRT) reirradiation, with concurrent pembrolizumab.

II. To assess the safety profile and estimate early clinical benefit of NBXTR3 activated by dose reduction intensity modulated radiation therapy (IMRT) or intensity modulated proton therapy (IMPT) reirradiation with concurrent pembrolizumab, in subjects with locoregional recurrent head and neck squamous cell carcinoma (HNSCC) not eligible for SBRT.

SECONDARY OBJECTIVES:

  1. To evaluate tumor response after NBTXR3 activated by SBRT reirradiation with concurrent pembrolizumab.

II. To evaluate tumor response after NBTXR3 activated by dose reduction IMRT/IMPT reirradiation with concurrent pembrolizumab.

III. To evaluate the safety profile of NBTXR3 activated by SBRT reirradiation with concurrent pembrolizumab.

IV. To evaluate time-to-event outcomes of NBTXR3 activated by SBRT reirradiation with concurrent pembrolizumab.

  1. To evaluate time-to-event outcomes of NBTXR3 activated by dose reduction IMRT/IMPT reirradiation with concurrent pembrolizumab.

EXPLORATORY OBJECTIVES:

  1. To evaluate lymphedema/fibrosis \& dysphagia-related toxicities and functional outcomes of treatment with NBTXR3 activated by SBRT or IMRT or IMPT reirradiation and concurrent pembrolizumab.

II. To assess functional and patient reported outcomes (PRO) of treatment with NBTXR3 activated by SBRT or IMRT or IMPT reirradiation and concurrent pembrolizumab.

III. To associate radiomic measurements with outcomes of treatment with NBTXR3 activated by SBRT or IMRT or IMPT reirradiation and concurrent pembrolizumab.

IV. To evaluate biomarkers of response in subjects treated with NBTXR3 activated by SBRT or IMRT or IMPT reirradiation and concurrent pembrolizumab.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT I: Patients receive NBTXR3 intratumorally (IT) on day 1. Patients then undergo SBRT every other day (QOD) on days 15-29. Beginning the first day of radiation therapy, patients also receive pembrolizumab intravenously (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: Patients receive NBTXR3 IT on day 1. Patients then undergo IMRT/IMPT every day (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.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for up to 5 years.

Being tested
Hafnium Oxide-containing Nanoparticles NBTXR3, Intensity-Modulated Proton Therapy, Intensity-Modulated Radiation Therapy, Pembrolizumab, Quality-of-Life Assessment
Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Hafnium Oxide-containing Nanoparticles NBTXR3Other

    Also called NBTXR3

    Given IT

  • Intensity-Modulated Proton TherapyProcedure or surgery

    Also called IMPT

    Undergo IMPT

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

    Undergo IMRT

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

  • Stereotactic Body Radiation TherapyRadiation

    Also called SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

    Undergo SBRT

Study groups in NCT04834349
Study groupRoleWhat they receive
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.
Receives: Other: Hafnium Oxide-containing Nanoparticles NBTXR3; Biological: Pembrolizumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Stereotactic Body Radiation Therapy
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.
Receives: Other: Hafnium Oxide-containing Nanoparticles NBTXR3; Procedure: Intensity-Modulated Proton Therapy; Radiation: Intensity-Modulated Radiation Therapy; Biological: Pembrolizumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression free survival (PFS)

    Will be estimated using the method of Kaplan-Meier. Median times and 95% confidence intervals will also be estimated.

    Measured: 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

  2. Early clinical benefit activated by SBRT reirradiation

    Defined as radiographic evidence of complete response (CR), partial response (PR) or stable disease (SD)

    Measured: At 6-months post radiation therapy (RT)

  3. 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.

    Measured: Up to 90 days post RT

  4. 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.

    Measured: 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)

  5. 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.

    Measured: From 90 days post RT to end of study (up to 5 years)

Secondary outcomes (7)

  1. Objective response rate

    Defined as complete or partial response per RECIST v1.1 in the target lesion(s), which are those injected with NBTXR3 and irradiated.

    All other malignant lesions that have not received NBTXR3 injection will be evaluated as per RECIST v1.1, i.e. as measurable or non-measurable lesions (according to their characteristics) and included for the determination of best objective response.

    Measured: Up to 5 years post treatment

  2. Overall response

    Evaluated as per RECIST v1.1

    Measured: Up to 5 years post treatment

  3. Incidence of acute 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.

    Measured: Up to 90 days post RT

  4. Local PFS

    Will be estimated using the method of Kaplan-Meier. Median times and 95% confidence intervals will also be estimated.

    Measured: 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

  5. Regional PFS

    Will be estimated using the method of Kaplan-Meier. Median times and 95% confidence intervals will also be estimated.

    Measured: 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

  6. Distant PFS

    Will be estimated using the method of Kaplan-Meier. Median times and 95% confidence intervals will also be estimated.

    Measured: From NBTXR3 injection to the radiographic and/or histological confirmation of a new lesion outside the head and neck region, or death from any cause, whichever occurs first, assessed up to 5 years

  7. Overall survival

    Will be estimated using the method of Kaplan-Meier. Median times and 95% confidence intervals will also be estimated.

    Measured: From NBTXR3 injection to death from any cause or EoS, whichever occurs first, assessed up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2021
  2. Study start9 Mar 2021
  3. Primary completion21 Nov 2022
  4. Study completion21 Nov 2022

Why it stopped: No participants were enrolled

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04834349
Sponsor's protocol ID
2020-0354
Other IDs
NCI-2021-00123, 2020-0354
Status last verified
Sep 2023
First submitted
5 Mar 2021
Last updated
13 Sep 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Hafnium Oxide-containing Nanoparticles NBTXR3, Intensity-Modulated Proton Therapy and Intensity-Modulated Radiation Therapy in people with Recurrent Head and Neck Squamous Cell Carcinoma and Unresectable Head and Neck Squamous Cell Carcinoma, run by M.D. Anderson Cancer Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 13 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (PFS) (time frame: 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). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04834349.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2023.

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