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Bioimmunoradiotherapy (Cetuximab/RT/Avelumab)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02938273
Recruitment Status : Completed
First Posted : October 19, 2016
Last Update Posted : December 11, 2019
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
The Netherlands Cancer Institute

Brief 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.

Condition or disease Intervention/treatment Phase
Carcinoma, Squamous Cell of Head and Neck Drug: avelumab Radiation: radiotherapy Drug: cetuximab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 1, 2017
Actual Primary Completion Date : June 26, 2019
Actual Study Completion Date : September 30, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Bioimmunoradiotherapy
Concurrent 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.
Drug: avelumab
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
Other Name: MSB0010718C

Radiation: radiotherapy
5 times a week, 7 weeks, total dose 70 Gy

Drug: cetuximab
loading dose 400 mg/m2 i.v. day -7, 250 mg/m2 i.v weekly wk 1-7
Other Name: erbitux

Primary Outcome Measures :
  1. occurence of grade 3-5 toxicity in new combination [ Time Frame: 6 months after start of treatment ]
    according to CTC 4.03

Secondary Outcome Measures :
  1. Overall Response Rate [ Time Frame: at week 10 and week 26 of treatment ]

Other Outcome Measures:
  1. differences in tumor microenvironment [ Time Frame: prior to treatment and at day 14 ]
    investigate therapy induced changes in tumor microenvironment in tissue biopsies through immunochemistry

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.
  • 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:

    1. Absolute Neutrophil Count (ANC) ≥1.5 x 109/L;
    2. Platelets ≥100 x 109/L;
    3. 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:

  1. Total serum bilirubin ≤1.5 x ULN;
  2. 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.

Exclusion Criteria:

- 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).
  • 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:

    1. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment
    2. 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
    3. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02938273

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Antoni van Leeuwenhoek
Amsterdam, Netherlands, 1066CX
Sponsors and Collaborators
The Netherlands Cancer Institute
Merck KGaA, Darmstadt, Germany
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Principal Investigator: Jan Paul de Boer, MD, PhD The Netherlands Cancer Institute
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: The Netherlands Cancer Institute Identifier: NCT02938273    
Other Study ID Numbers: N16BIR
First Posted: October 19, 2016    Key Record Dates
Last Update Posted: December 11, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Head and Neck Neoplasms
Neoplasms by Site
Antineoplastic Agents, Immunological
Antineoplastic Agents