Tolerance and Efficacy of Pembrolizumab or Cetuximab Combined With RT in Patients With Locally Advanced HNSCC
Condition: Squamous Cell Carcinoma of the Head and Neck
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
Study type: Interventional
Phase: Phase 2

Summary: 
      The general aim of the study is to evaluate the anti-tumour activity and the tolerance
      profile of Pembrolizumab + RT in comparison to cetuximab + RT in patients with locally
      advanced HNSCC and to explore potential correlations between treatment outcome and the immune
      landscape.
    

Detailed description: 
      A majority of HNSCC are locally advanced and commonly treated with concomitant
      chemo-radiotherapy (CT-RT). However, a large proportion of patients with locally advanced
      stage are not suitable for receiving cisplatinum-based chemotherapy (CT) concomitant with
      radiotherapy (RT) either due to age, general and/or medical condition(s).

      An alternative standard treatment has been established, combining RT and cetuximab.

      However, both CT-RT and cetuximab-RT which are considered as standard approaches in locally
      advanced non operated HNSCC are associated with poor outcome in patients with the most
      advanced T stage (T4) and/or N stage (>=N2) and/or HPV negative tumours. A new and promising
      approach could target immune response.

      Pembrolizumab is a high-affinity monoclonal anti-PD1 antibody which showed antitumor activity
      in melanoma and NSCLC. In the KEYNOTE-012 (multi-center, nonrandomized Phase Ib HNSCC),
      Pembrolizumab was well tolerated and safe with no serious drug related AEs reported. About
      51% (26/51) of patients had decreased tumor burden which was seen both in HPV (-) and HPV(+)
      HNSCC.

      This observation led to the hypothesis generated in the current study that Pembrolizumab is
      potentially a very active drug in HNSCC and that the combination of Pembrolizumab with
      radiotherapy will be well tolerated, given the very good toxicity profile of the drug and
      will improve the outcome of patients with locally advanced HNSCC non suitable for CT-RT, as
      compared to the treatment of reference combining cetuximab and RT.
    

Intervention name(s): Pembrolizumab; Cetuximab; Radiotherapy
Intervention type(s): Drug; Drug; Radiation
Intervention description(s): 200mg IV infusion every 3 weeks, i.e. on day 1, 22, 43 during the course of radiotherapy.
Radiotherapy will be delivered daily for 5 days per week to a total dose of 69.96 Gy in 2.12 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 radiotherapy.
Radiotherapy will be delivered daily for 5 days per week to a total dose of 69.96 Gy in 2.12 Gy daily fractions over 6.5 weeks (33 fractions).; Radiotherapy will be delivered daily for 5 days per week to a total dose of 69.96 Gy in 2.12 Gy daily fractions over 6.5 weeks (33 fractions).
Other intervention name(s): antibody; antibody; Conventional Radiotherapy
Intervention MeSH terms: Pembrolizumab; Cetuximab; Antibodies; Immunoglobulins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Determine the tolerance and efficacy of Pembrolizumab