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Carcinoma, Squamous Cell of Head and NeckPhase 1NCT02938273

Bioimmunoradiotherapy (Cetuximab/RT/Avelumab)

A Phase 1 study testing avelumab, radiotherapy and cetuximab in people with Carcinoma, Squamous Cell of Head and Neck, run by The Netherlands Cancer Institute at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is an open-label phase IB trial with Bioimmunoradiotherapy, i.e. concurrent radiotherapy with intravenous administration of cetuximab and avelumab followed by avelumab maintenance therapy in patients with locally advanced head and neck cancer, unfit for cisplatin. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
avelumab, radiotherapy and cetuximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteNetherlands
Study dates
1 Feb 2017to 30 Sep 2019
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

  • Be willing and able to provide written informed consent for the trial.
  • Be ≥18 years of age on day of signing informed consent.
  • WHO Performance Status 0,1 or 2
  • Have histologically confirmed Locally Advanced (i.e. stage III or IV) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx and larynx.
  • Unfit for concurrent chemoradiation with cisplatin, e.g. GFR < 60 ml/min, cardiovascular co-morbidity, hearing loss or polyneuropathy or written refusal for treatment with chemotherapy
  • Be willing to provide tissue for tumor microenvironment analysis from archival tumor material (i.e. formalin fixed, paraffin embedded (FFPE) tumor tissue block not older than 42 days before start of treatment) or newly obtained core or excisional biopsy, and willingness to provide a core or excisional biopsy at day 14 (±2 days) after start of treatment.
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  • Have at least one measurable lesion as defined by RECIST 1.1.
  • Be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
  • Demonstrate adequate organ function, i.e. adequate bone marrow function, including:
  • Absolute Neutrophil Count (ANC) ≥1.5 x 109/L;
  • Platelets ≥100 x 109/L;
  • Hemoglobin ≥6 mmol/L. Adequate renal function, i.e. estimated creatinine clearance ≥30 mL/min as calculated using the Cockcroft-Gault (CG) equation (or local institutional standard method).
  • Adequate liver function, including:
  • Total serum bilirubin ≤1.5 x ULN;
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
  • Have a negative serum pregnancy test at screening (for females of childbearing potential).
  • Both male and female subjects should agree to use highly effective contraception if the risk of conception exists. (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential and men able to father a child must agree to use 2 highly effective contraception, defined as methods with a failure rate of less than 1 % per year.) Highly effective contraception is required throughout the study and for at least 120 days after Avelumab treatment.

Who cannot join

  • Prior treatment with: Systemic therapy, radiotherapy or surgery directed at locally advanced SCCHN. Immunotherapy with IL-2, IFN-α, or anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
  • A diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Current or prior use of immunosuppressive medication within 7 days prior to registration, except the following:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra-articular injection);
  • Systemic corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent;
  • Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
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  • Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of partially controlled asthma Global Initiative for Asthma 2011.
  • Known prior or suspected hypersensitivity to study drugs or any component in their formulations.
  • Diagnosis of any other malignancy within 5 years prior to start of treatment except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (e.g. surgery, radiation, or castration).
  • Significant acute or chronic infections including, among others:
  • Known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive)
  • Prior organ transplantation, including allogeneic stem cell transplantation
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent, except the following:
  • Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment
  • Subjects requiring hormone replacement with corticosteroids if the steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or 10 mg equivalent prednisone per day
  • Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation)
  • Persisting toxicity related to prior therapy of Grade >1; however, alopecia and sensory neuropathy Grade ≤ 2 is acceptable
  • Pregnancy or lactation
  • Known alcohol or drug abuse
  • All other significant diseases (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the Investigator, might impair the subject's tolerance of trial treatment
  • Any psychiatric condition that would prohibit the understanding or rendering of informed consent
  • Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines).
  • Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis or symptomatic pulmonary embolism.
  • Subjects with brain metastases

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Antoni van Leeuwenhoek

    Amsterdam, 1066CX

Other trials in Netherlands

About this study

Official title: Bioimmunoradiotherapy (BIR) With Concurrent Avelumab, Cetuximab and Radiotherapy as First Line Treatment in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck. A Feasibility Study in Patients Unfit for Cisplatin

This is an open-label phase IB trial with Bioimmunoradiotherapy, i.e. concurrent radiotherapy with intravenous administration of cetuximab and avelumab followed by avelumab maintenance therapy in patients with locally advanced head and neck cancer, unfit for cisplatin.

Being tested
avelumab, radiotherapy, cetuximab
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.

  • avelumabDrug

    Also called MSB0010718C

    Avelumab10 mg/kg i.v. at day -7, 7, 21,35 + maintenance therapy i.e avelumab10 mg/kg i.v. every 2 weeks for 6 months

  • radiotherapyRadiation

    5 times a week, 7 weeks, total dose 70 Gy

  • cetuximabDrug

    Also called erbitux

    loading dose 400 mg/m2 i.v. day -7, 250 mg/m2 i.v weekly wk 1-7

Study groups in NCT02938273
Study groupRoleWhat they receive
BioimmunoradiotherapyExperimentalConcurrent Radiation therapy (i.e. 5 times a week, 7 weeks, total dose 70 Gy) with cetuximab (loading dose 400 mg/m2 i.v. day -7, 250 mg/m2 i.v weekly wk 1-7) and Avelumab10 mg/kg i.v. at day -7, 7, 21,35 + maintenance therapy i.e avelumab10 mg/kg i.v. every 2 weeks for 6 months (wk 8,10, 12, 14, 16, 18, 20, 22, 24, 26.
Receives: Drug: avelumab; Radiation: radiotherapy; Drug: cetuximab

What is being measured

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

  1. occurence of grade 3-5 toxicity in new combination

    according to CTC 4.03

    Measured: 6 months after start of treatment

Secondary outcomes (1)

  1. Overall Response Rate

    Measured: at week 10 and week 26 of treatment

Timeline

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

  1. First posted19 Oct 2016 (estimated)
  2. Study start1 Feb 2017
  3. Primary completion26 Jun 2019
  4. Study completion30 Sep 2019

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
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02938273
Sponsor's protocol ID
N16BIR
Status last verified
Dec 2019
First submitted
26 Sep 2016
Last updated
11 Dec 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Elbers JBW, Al-Mamgani A, Tesseslaar MET, van den Brekel MWM, Lange CAH, van der Wal JE, Verheij M, Zuur CL, de Boer JP. Immuno-radiotherapy with cetuximab and avelumab for advanced stage head and neck squamous cell carcinoma: Results from a phase-I trial. Radiother Oncol. 2020 Jan;142:79-84. doi: 10.1016/j.radonc.2019.08.007. Epub 2019 Sep 26.

    PubMed 31563412

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing avelumab, radiotherapy and cetuximab in people with Carcinoma, Squamous Cell of Head and Neck, run by The Netherlands Cancer Institute 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 17 inclusion and 25 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: finished, as of the sponsor's last update on 11 Dec 2019. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

occurence of grade 3-5 toxicity in new combination (time frame: 6 months after start of treatment). 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 NCT02938273, which also lists 1 linked publication.

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 11 Dec 2019.

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