Biomarker-based Study in R/M SCCHN

Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Study ID
NCT03088059
Phase
PHASE2
Status
Unknown

Conditions

  • Carcinoma, Squamous Cell of Head and Neck

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Afatinib — DRUG
    Afatinib 40 mg given orally, once daily, 1 cycle is 28 days
  • Palbociclib — DRUG
    Palbociclib 125 mg given orally, once daily, 1 cycle is 28 days (21 days on treatment, then 7 days off)
  • standard of care — DRUG
    Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care
  • IPH2201 — DRUG
    protocol v2.0 and 2.1 : Monalizumab 10mg/kg given intravenously over 60 minutes, once every 14 days, 1 cycle is 14 days protocol v4.0 : Monalizumab 750mg given intravenously over 60 minutes, once every 28 days, 1 cycle is 28 days
  • Durvalumab — DRUG
    Durvalumab 1500mg given intravenously over 60 minutes, once every 28 days, 1 cycle is 28 days
  • Niraparib — DRUG
    Niraparib 300 mg given orally, once daily, 1 cycle is 28 days
  • INCAGN01876 — DRUG
    INCAGN01876 300 mg given intravenously over 30 minutes, once every 14 days, 1 cycle is 28 days

Study Details

This is a biomarker-driven trial that will enroll patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing after first-line platinum-based chemotherapy. Based on potential biomarkers and molecular alterations identified in the biopsy from the central platform, patients will be allocated in different cohorts. There will be biomarker-positive patient cohorts and immunotherapy cohorts.

Key Dates

Start date
Nov 16, 2017
Status verified
Nov 2023
Primary completion
Jun 30, 2025
Completion
Dec 31, 2025

Study Design

Enrollment
340 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Patient Cohort B1
    Patients who are p16 negative and have an EGFR amplification/mutation or PTEN high or HER2 mutation/amplification will be randomized between afatinib or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care).
  • Experimental: Patient Cohort B2
    Patients who are p16 negative and cetuximab naïve will be randomized between afatinib or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)
  • Experimental: Patient Cohort B3
    Patients who are p16 negative and have an amplification of CCND1 will be randomized between palbociclib or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)
  • Experimental: Patient Cohort B4
    Patients who are p16 negative and 'platinum sensitive' SCCHN will receive niraparib
  • Experimental: Patient Cohort B5
    Patients whith oropharyngeal cancer and which are p16 positive will receive niraparib
  • Experimental: Patient Cohort I1
    Patients who are anti-PD(L)1-naïeve or resistant (primary or secondary resistance) will receive IPH2201 antibody (monalizumab).
  • Experimental: Patient Cohort I2
    Patient who are PD(L)1 pretreated will be randomized between monalizumab + durvalumab or the standard of care (Methotrexate, Paclitaxel, Docetaxel, Carboplatin, 5-Fluorouracil, Bleomycine, Gemcitabine, Mitomycine or Best supportive care)
  • Experimental: Patient Cohort I3
    Patient who are progressing prior PD(L)1 after having received at least 2 months of anti-PD(L)-1 will receive INCAGN01876.

Primary Outcome Measure

Progression Free Survival Rate (PFSR) at week 16 [ Time Frame: The Progression Free Survival Rate (PFSR) analysis will be performed at week 16 for each patient in cohorts 1, 2 and 3. ]

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