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Oral Cavity Squamous Cell CarcinomaPhase 1NeoNivoNCT03843515

Neoadjuvant Nivolumab for Oral Cancer Combined With FDG and Anti-PD-L1 PET/CT Imaging for Response Prediction

A Phase 1 study testing Nivolumab in people with Oral Cavity Squamous Cell Carcinoma, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Safety and tolerability of neoadjuvant nivolumab for locally advanced resectable oral cancer, combined with [18F]BMS-986192 / [18F]-FDG PET imaging and immunomonitoring for response prediction Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Oral Cavity Squamous Cell Carcinoma
What is being tested?
Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteNetherlands
Study dates
11 Apr 2019to 31 Aug 2022
Phase
Phase 1
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

  • Have a histologically confirmed diagnosis of locally advanced oral cancer (stage III/IV) which is planned for treatment with curative intent including surgical resection.
  • Be willing and able to provide written informed consent/assent for the trial.
  • Be more then 18 years of age on day of signing informed consent.
  • Must agree to provide tissue from fresh tumor biopsy pretreatment and from the surgical resection material to determine the actual PD-L1 status and perform immunomonitoring/DNA/RNA profiling.
  • Willing to allow up to two additional biopsies when baseline [18F]BMS-986192 PET /[18F]-FDG PET scans show heterogeneous and/or discrepant uptake.
  • Have a performance status of 0-1 on the ECOG Performance Scale (Appendix 2).
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  • Demonstrate adequate organ function as defined in table 1. All screening labs should be performed within 2 weeks before any study imaging procedures are performed
  • Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception during the study and for 23 weeks after the last dose of nivolumab. Women who are not of childbearing potential (i.e. who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception (Appendix 4)
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception during the study and for 31 weeks after the last dose of nivolumab (Appendix 4).

Who cannot join

  • Is currently participating in or has participated in a study of an investigational agent within 4 weeks of the first dose of treatment or has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
  • Has had another known invasive malignancy within the previous 5 years and/or has had surgery, chemotherapy, targeted small molecule therapy or radiation therapy within 5 years for a known malignancy prior to study day 0.
  • Has a known current additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
  • If subject received major surgery for any other reason, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of day -5. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
  • Has an active autoimmune disease requiring systemic steroid treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids.
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  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 23 weeks after the last dose of trial treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways.
  • Has a known history of Human Immunodeficiency Virus (HIV) infection (HIV 1/2 antibodies).
  • Has known active Hepatitis B or C.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • VU University medical center

    Amsterdam, North Holland, 1081 HV

Other trials in Netherlands

About this study

Official title: "Safety and Tolerability of Neoadjuvant Nivolumab for Locally Advanced Resectable Oral Cancer Combined With [18F] BMS-986192 / [18F] -FDG PET Imaging and Immunomonitoring for Response Prediction"

Safety and tolerability of neoadjuvant nivolumab for locally advanced resectable oral cancer, combined with [18F]BMS-986192 / [18F]-FDG PET imaging and immunomonitoring for response prediction

Read the detailed description

Intensive treatment regimens with surgical resection and adjuvant (chemo)radiotherapy of patients with locally advanced oral cancer still result in only 50-60% cure rate, leaving a substantial group of patients who will develop a local recurrence or distant metastases with minimal curative salvage treatment options. Treatment with anti-PD-1 monoclonal antibodies (mAbs) has shown promise in patients with recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC). This supports the hypothesis that including treatment with anti PD-1 mAb nivolumab could improve the outcome for patients with locally advanced oral cancer resulting in a higher cure rate. Response rate with nivolumab was below 20% in unselected patients with r/m HNSCC. Therefore, biomarkers for response are urgently needed. Tumor PD-L1 immunohistochemistry (IHC) was shown to be related to nivolumab response but cannot be reliably used for patient selection. Temporal and spatial heterogeneity of tumor PD-L1 expression (within and between tumor lesions) might be responsible for its suboptimal predictive value as biomarker of response. Therefore there is a need to further evaluate tumor PD-L1 expression as predictive biomarker, as well as exploring alternatives. Serial PET imaging with [18F]BMS-986192 (anti-PD-L1 tracer) and [18F]-FDG has the potential to provide whole body information of the patient over time, at baseline as well as on treatment and represents a biomarker for toxicity and efficacy. In addition, we will investigate the immunophenotype of the patient and tumor, as well as the presence of neoantigens and other potential other biomarkers such as plasma vesicle miRNAs.

Being tested
Nivolumab
Keywords
head and neck squamous cell carcinoma, nivolumab, PD-L1, PET/CT, neoadjuvant
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.

  • NivolumabDrug

    Also called Neoadjuvant nivolumab

    Neoadjuvant nivolumab flat dose 400mg

Study groups in NCT03843515
Study groupRoleWhat they receive
Neoadjuvant nivolumabExperimentalAll subject will receive 400mg flat dose nivolumab in the neoadjuvant setting
Receives: Drug: Nivolumab

What is being measured

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

  1. (Serious) adverse events

    Adverse events

    Measured: untill 100 days after last study drug administration

  2. SUV values

    SUVpeak/mean/max of tumor lesions on FDG-PET/anti-PD-L1 PET

    Measured: 2 years

Secondary outcomes (1)

  1. Correlation between PET data and Blood/Tissue markers

    The correlation between continuous values as SUV and the categorical variables tissue PD-1 and PD-L1 IHC will be assessed for each tumor lesion. Correlation with immuno-monitoring analysis in tumor tissue/lymph nodes and blood, plasma vesicle miRNAs from blood, as well as DNA/RNA profiling in tumor tissue at baseline and at surgery will be assessed.

    Measured: 2 years

Timeline

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

  1. First posted18 Feb 2019
  2. Study start11 Apr 2019
  3. Primary completion30 Nov 2021 (estimated)
  4. Study completion31 Aug 2022 (estimated)

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Phase I safety and feasibility study with additional pilot biomarker assessments
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03843515
Sponsor's protocol ID
2018-002643
Other IDs
2018
Acronym
NeoNivo
Status last verified
Oct 2021
First submitted
13 Feb 2019
Last updated
8 Oct 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Nivolumab in people with Oral Cavity Squamous Cell Carcinoma, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.

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 9 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 8 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

Results are not available in the source record.

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?

(Serious) adverse events (time frame: untill 100 days after last study drug administration). The study lists 2 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 NCT03843515.

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 8 Oct 2021.

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