Gerandomiseerde studie van Avelumab-cetuximab-radiotherapie versus SOC's in LA SCCHN (REACH) (REACH)
Een gerandomiseerde fase III-studie van Avelumab-cetuximab-radiotherapie versus zorgstandaarden bij lokaal gevorderd plaveiselcelcarcinoom van het hoofd-halsgebied
The purpose of this study is to demonstrate that treatment with avelumab in combination with RT-cetuximab is superior to standard of care (SOC) cisplatin-RT and/or to SOC RT-cetuximab alone in terms of progression-free survival (PFS) in front-line patients with locally advanced SCCHN.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
This open-label, randomized, controlled, multicenter phase III study will include 688 patients with LA SCCHN (420 fit for HD cisplatin and 268 unfit for HD cisplatin), histologically confirmed who had not received previous treatment for this setting. The study is designed with the primary objective of demonstrating that treatment with avelumab in combination with cetuximab-RT is superior to SOC Cisplatin-RT or cetuximab-RT alone in terms of PFS. Randomization will assign the 2 treatment arms of each cohort with a 1:1 ratio. In each cohort (fit for cisplatin and unfit for cisplatin), the randomization will be stratified for the 2 most established prognostic factors N stage (N0-N1 vs N2-3) and p16 expression (OPC p16+ versus OPC p16- or non OPC). All patients will be followed until death or at least 60 months.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 3
Contacten en locaties
Studie Locaties
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Lorient, Frankrijk, 56322
- Centre Hospitalier Bretagne Sud
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
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Age ≤ 80 years
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Performance Status ECOG 0-1
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Squamous cell carcinoma, previously untreated
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Stage III, stage IVa (i.e. operable, but not operated) or IVb (non resectable)
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Oral cavity, oropharynx, hypopharynx or larynx
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Availability of pre-treatment tumour tissue sample (for p16 & PD -L1 expression, TILs and immune landscape)
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Recording of alcohol consumption and smoking history
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Determination of the patient's ability to receive cisplatin 100 mg /m2 for 3 cycles (fit / unfit)*
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Written informed consent
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Criteria for determining if a patient is fit for receiving high dose cisplatin:
- Calculated creatinin clearance ≥ 60 mL/min as determined by the modified. method of Cockcroft and Gault or by the EDTA method
- Absolute neutrophil count ≥1 500/μL, platelets ≥100 000/μL, hemoglobin ≥ 10 g/dL, aspartate (AST) and alanine transaminase (ALT) less than 2 times the upper limit of the normal range (ULN), total bilirubin ≤ 1.5 mg/dL, serum albumin > 35 g/L
- Peripheral neuropathy < grade 2
- No clinical hearing loss (confirmed by audiogram)
- Cardiac function compatible with hyperhydration; Left ventricular ejection fraction within the institutional normal ranges as measured by echocardiogram
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Exclusion Criteria:
- Nasopharyngeal, paranasal sinuses, nasal cavity tumors or thyroid cancers
- Squamous cell carcinoma involving cervical neck nodes with unknown primary site
- Metastatic disease (stage IVc)
- Viral infection (HIV, Hepatitis B/C)
- Autoimmune disease
- Immunodeficiency or immunosuppressive therapy
- Active CNS disease
- Interstitial lung disease
- Active infection
- Any prior or current treatment for invasive head and neck cancer. This will include but is not limited to: prior tyrosine kinase inhibitors, any monoclonal antibody, induction chemotherapy, prior surgical resection or RT, or use of any investigational agent
- Weight loss of > 10% during the last 4 weeks (except if renutrition with a feeding tube is planned before the onset of treatment or is ongoing)
- Concurrent treatment with any other systemic anti-cancer therapy that is not specified in the protocol
- Concomitant treatment with any drug on the prohibited medication list such as live vaccines
- History of other malignancy within the last 3 years (exception of in situ carcinoma and skin carcinomas)
- Significant disease which, in the judgment of the investigator, as a result of the medical interview, physical examinations, or screening investigations would make the patient inappropriate for entry into the trial
- Known hypersensitivity reaction to study drugs
- Any social, personal, medical and/or psychological factor(s) that could interfere with the observance of the patient to the protocol and/or the follow-up and/or the signature of the informed consent.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Actieve vergelijker: Arm A Patient FIT
Lead-in phase (Day-8) : no treatment Concomitant radiotherapy phase : Radiotherapy by IMRT + cisplatin 100mg/m2 Maintenance phase : no treatment until follow-up phase |
100 mg/m² IV after hyperhydration and at a maximal rate of 1 mg/min, on days 1, 22, 43. RT will be performed using IMRT (intensity modulated radiotherapy), with a simultaneous integrated boost (SIB) technique. RT dose to the GTV will be 69.96 Gy in 2.12 Gy daily fractions over 6.5 weeks (33 fractions). Prophylactic dose will be 52.8 Gy in 1.6 Gy daily fractions over 6.5 weeks (33 fractions). |
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Experimenteel: Arm B Patient FIT
Lead-in phase (Day-8) : Cetuximab 400mg/m2 and avelumab 10mg/kg Concomitant radiotherapy phase : Radiotherapy by IMRT + cetuximab 250mg/m2 and avelumab 10mg/kg Maintenance phase : avelumab 10mg/kg every 2 weeks during 12 months |
RT will be performed using IMRT (intensity modulated radiotherapy), with a simultaneous integrated boost (SIB) technique. RT dose to the GTV will be 69.96 Gy in 2.12 Gy daily fractions over 6.5 weeks (33 fractions). Prophylactic dose will be 52.8 Gy in 1.6 Gy daily fractions over 6.5 weeks (33 fractions). Loading dose of 400 mg/m² IV on Day-8, followed by weekly dose of 250 mg/m² IV during the whole course of RT. IV infusion of avelumab (10 mg/kg over 1 hour) once every 2 weeks. Avelumab will start on Day-8 together with cetuximab and subsequently every 2 weeks during the course of RT. Avelumab with be continued every 2 weeks for an additional 12 months following RT. |
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Experimenteel: Arm C Patient UNFIT
Lead-in phase (Day-8) : Cetuximab 400mg/m2 and avelumab 10mg/kg Concomitant radiotherapy phase: Radiotherapy by IMRT + cetuximab 250mg/m2 and avelumab 10mg/kg Maintenance phase : avelumab 10mg/kg every 2 weeks during 12 months |
RT will be performed using IMRT (intensity modulated radiotherapy), with a simultaneous integrated boost (SIB) technique. RT dose to the GTV will be 69.96 Gy in 2.12 Gy daily fractions over 6.5 weeks (33 fractions). Prophylactic dose will be 52.8 Gy in 1.6 Gy daily fractions over 6.5 weeks (33 fractions). Loading dose of 400 mg/m² IV on Day-8, followed by weekly dose of 250 mg/m² IV during the whole course of RT. IV infusion of avelumab (10 mg/kg over 1 hour) once every 2 weeks. Avelumab will start on Day-8 together with cetuximab and subsequently every 2 weeks during the course of RT. Avelumab with be continued every 2 weeks for an additional 12 months following RT. |
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Actieve vergelijker: Arm D Patient UNFIT
Lead-in phase (Day-8): Cetuximab 400mg/m2 Concomitant radiotherapy phase: Radiotherapy by IMRT + cetuximab 250mg/m2 Maintenance phase : no treatment until follow-up phase |
RT will be performed using IMRT (intensity modulated radiotherapy), with a simultaneous integrated boost (SIB) technique. RT dose to the GTV will be 69.96 Gy in 2.12 Gy daily fractions over 6.5 weeks (33 fractions). Prophylactic dose will be 52.8 Gy in 1.6 Gy daily fractions over 6.5 weeks (33 fractions). Loading dose of 400 mg/m² IV on Day-8, followed by weekly dose of 250 mg/m² IV during the whole course of RT. |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Progression free survival
Tijdsspanne: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 74 months
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Time between randomization and the first event among progression (per modified Response Evaluation Criteria in Solid Tumors (RECIST) version v1.1) and death, whatever the cause of death. |
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 74 months
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Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
|---|---|
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Algemeen overleven
Tijdsspanne: Vanaf de datum van randomisatie tot de datum van overlijden door welke oorzaak dan ook, beoordeeld tot 74 maanden
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Vanaf de datum van randomisatie tot de datum van overlijden door welke oorzaak dan ook, beoordeeld tot 74 maanden
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Veiligheid: acute bijwerkingen beoordeeld door NCI CTCAE v4.03
Tijdsspanne: Vanaf de datum van randomisatie tot het einde van de studie, beoordeeld tot 74 maanden
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Vanaf de datum van randomisatie tot het einde van de studie, beoordeeld tot 74 maanden
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Medewerkers en onderzoekers
Medewerkers
Publicaties en nuttige links
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Geschat)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Neoplasmata per site
- Neoplasmata
- Neoplasmata per histologisch type
- Neoplasmata, glandulair en epitheel
- Carcinoom
- Carcinoom, plaveiselcel
- Plaveiselcelcarcinoom van hoofd en hals
- Hoofd- en nekneoplasmata
- Aminozuren, peptiden en eiwitten
- Eiwitten
- Antilichamen, monoklonaal, gehumaniseerd
- Antilichamen, monoklonaal
- Antilichamen
- Immunoglobulinen
- Immunoproteïnen
- Bloedeiwitten
- Serum -globulines
- Globulines
- Anorganische chemicaliën
- Chloorverbindingen
- Stikstofverbindingen
- Platinumverbindingen
- Cetuximab
- Cisplatine
- evelumab
Andere studie-ID-nummers
- GORTEC 2017-01
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Informatie over medicijnen en apparaten, studiedocumenten
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