Randomized Phase III Trial of Sequential Re-Radiochemotherapy and Pembrolizumab Versus Immuno(Chemo)Therapy for Locoregionally Recurrent PD-L1 Positive HNSCC (CPS≥1)
Prospective, open-label, randomized controlled phase III trail that aims to investigate whether Re-Radiochemotherapy (Re-RCT) and sequential immunotherapy with pembrolizumab improves overall survival compared to the standard treatment with pembrolizumab alone (± chemotherapy) in locoregionally recurrent PD-L1 positive (CPS≥1) HNSCC.
• Written informed consent obtained from the subject prior to performing any protocol-related procedures.
• Age ≥ 18 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• Locoregionally recurrent or second primary HNSCC.
• Histological confirmation of HNSCC.
• Tumor is surgically not resectable or surgical resection bears great potential for relevant functional morbidity or patient refuses surgery.
• No distant metastases (cM0).
• PD-L1 combined positive score (CPS) ≥1 according to local pathological PD-L1 assessment. A validated test must be used in an accredited laboratory.
• Prior radio(chemo)therapy of the neck (time interval ≥ 6 months).
• Adequate normal organ and marrow function as defined: Haemoglobin ≥ 9.0 g/dL; Leukocytes (WBC) ≥ 3,000 per mm3or Neutrophils ≥ 1,500 per mm3; Platelet count \> 100,000 per mm3.
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology).
• AST (SGOT) / ALT (SGPT) ≤ 2.5 x institutional ULN.
• Creatinine Clearance ≥ 40ml/min (calculated from serum creatinine using the Cockcroft-Gault formula).
• Female subject of childbearing potential should have a negative serum pregnancy within 72 hours prior to receiving the first dose of RT and/or the first dose of pembrolizumab. A highly sensitive pregnancy test must be used.
• Female subjects of childbearing potential must be willing to use a highly effective contraceptive measure (see also Section 7.1.9 Contraception and pregnancy testing during the trial). Highly effective contraception is required for the course of the trial through 120 days after the last dose of trial therapy.
• Generative male subjects must agree to use a highly effective method of contraception (see also Section 7.1.9 Contraception and pregnancy testing during the trial), starting with the first dose of trial therapy through 120 days after the last dose of trial therapy.
• Subject is willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits and examinations including.