- ICH GCP
- Register voor klinische proeven in de VS.
- Klinische proef NCT02938273
Bioimmunoradiotherapy (Cetuximab/RT/Avelumab)
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
Studie Overzicht
Toestand
Interventie / Behandeling
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 1
Contacten en locaties
Studie Locaties
-
-
-
Amsterdam, Nederland, 1066CX
- Antoni van Leeuwenhoek
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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:
- 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.
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:
- 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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
---|---|
Experimenteel: 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.
|
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
Andere namen:
5 times a week, 7 weeks, total dose 70 Gy
loading dose 400 mg/m2 i.v.
day -7, 250 mg/m2 i.v weekly wk 1-7
Andere namen:
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
---|---|---|
occurence of grade 3-5 toxicity in new combination
Tijdsspanne: 6 months after start of treatment
|
according to CTC 4.03
|
6 months after start of treatment
|
Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
---|---|
Overall Response Rate
Tijdsspanne: at week 10 and week 26 of treatment
|
at week 10 and week 26 of treatment
|
Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
---|---|---|
differences in tumor microenvironment
Tijdsspanne: prior to treatment and at day 14
|
investigate therapy induced changes in tumor microenvironment in tissue biopsies through immunochemistry
|
prior to treatment and at day 14
|
Medewerkers en onderzoekers
Sponsor
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Jan Paul de Boer, MD, PhD, The Netherlands Cancer Institute
Publicaties en nuttige links
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Neoplasmata per histologisch type
- Neoplasmata
- Neoplasmata per site
- Neoplasmata, glandulair en epitheel
- Hoofd- en nekneoplasmata
- Neoplasmata, plaveiselcel
- Carcinoom
- Carcinoom, plaveiselcel
- Plaveiselcelcarcinoom van hoofd en hals
- Antineoplastische middelen
- Antineoplastische middelen, immunologisch
- Avelumab
- Cetuximab
Andere studie-ID-nummers
- N16BIR
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
Klinische onderzoeken op avelumab
-
Merck KGaA, Darmstadt, GermanyVoltooid
-
Clinique Neuro-OutaouaisVoltooidGlioblastoma Multiforme van de hersenenCanada
-
Promontory Therapeutics Inc.Pfizer; EMD SeronoVoltooidNiet-kleincellige longkanker (NSCLC)Verenigde Staten, Zwitserland
-
Vaccinex Inc.University of RochesterWervingGemetastaseerd pancreasadenocarcinoomVerenigde Staten
-
PfizerBeëindigdNeoplasmata van de urineblaas | Blaaskanker | Urotheelcarcinoom | Blaas TumorenCanada
-
Samsung Medical CenterMerck KGaA, Darmstadt, GermanyActief, niet wervendLymfoom, extranodale NK-T-celKorea, republiek van
-
4SC AGMerck KGaA, Darmstadt, GermanyIngetrokken
-
AHS Cancer Control AlbertaEMD Serono; Alberta Cancer FoundationWervingPlaveiselcelcarcinoom van de huidCanada
-
McGill University Health Centre/Research Institute...WervingMaag Adenocarcinoom | Adenocarcinoom van de slokdarmCanada
-
Vaccinex Inc.Merck KGaA, Darmstadt, GermanyVoltooidCarcinoom, niet-kleincellige longVerenigde Staten