Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Durvalumab

Tremelimumab

Antineoplastic Agents, Immunological

Durvalumab (1500 mg,q4W) + Tremelimumab (75 mg, q4W / since Amendment 3: 300 mg absolute dose d5) for up to a maximum of 4 doses/cycles combined with radiotherapy (35 x 2.0/1.8/1.6 Gy) followed by durvalumab monotherapy 1500mg via IV infusion q4W, starting 4 weeks after the last infusion of the combination, for up to a maximum of 8 additional durvalumab doses.

Patients with an increased CD8+ tumor infiltrating immune cell density and at least clinically stable disease will receive radioimmunotherapy with the PD-L1 Inhibitor Durvalumab and the CTLA4-Inhibitor Tremelimumab (altogether 4 doses q4w including the induction dose) followed by maintenance therapy with Durvalumab (8 additional doses q4w).

Durvalumab + Tremelimumab + RT

Rainer Fietkau, Prof.

Wilfried Budach, Prof.

Claus Rödel, Prof.

Markus Hecht, M.D.

Udo Gaipl, Prof.

First-line treatment of locally advanced HNSCC with double checkpoint blockade and radiotherapy dependent on intratumoral CD8+ T cell Infiltration.

This is a single arm, open-label, prospective, non-randomized Phase II clinical trial of locally advanced HNSCC with double checkpoint blockade and radiotherapy dependent on intratumoral CD8+ T cell Infiltration.

All patients will initially be treated with the PD-L1 inhibitor Durvalumab (1500 mg q4w) and the CTLA-4 Inhibitor Tremelimumab (75 mg q4w / since Amendment 3 (01.04.2020): 300 mg absolute dose d5) and one cycle with Cisplatin (30mg/m² d1-3) and Docetaxel (75mg/m² d1). Treatment response will be evaluated clinically by endoscopy with biopsy. Changes of the CD8+ T cell density in the second biopsy compared to the first one before therapy will be used for patient selection. Patients with a stable or decreased CD8+ tumor infiltrating immune cell density or clinical progressive disease will receive standard CRT outside the trial. For these patients toxicity will be monitored until the first dose of the subsequent standard CRT. Patients with an increased CD8+ tumor infiltrating immune cell density and at least clinically stable disease will receive radioimmunotherapy with the PD-L1 Inhibitor Durvalumab and the CTLA4-Inhibitor Tremelimumab (altogether 4 doses q4w including the induction dose) followed by maintenance therapy with Durvalumab (8 additional doses q4w). The primary endpoint is feasibility. Feasibility criteria are receiving the protocol treatment until cycle 6 of antibody treatment and absence of any of the DLT defined in the protocol. A feasibility rate of ≥80% is expected. The efficacy of radioimmunotherapy and predictive character of changes of CD8+ tumor infiltrating immune cells after induction chemo-immunotherapy are further endpoints. The follow up period will be two years after the completion of radiotherapy.

Radiotherapy With Double Checkpoint Blockade of Locally Advanced HNSCC

First-line Treatment of Locally Advanced HNSCC With Double Checkpoint Blockade and Radiotherapy Dependent on Intratumoral CD8+ T Cell Infiltration (CheckRad-CD8, EudraCT NUMBER: 2017-003226-33)

Longitudinal analysis of the immune phenotype in the peripheral blood.

Feasibility means the number of participants receiving the protocol treatment

Changes of the CD8+ T cell density in the second biopsy compared to the first one before therapy will be used for patient selection.

Feasibility means the number of dose-limiting toxicities of Grade 3 or higher toxicity that occurs during the trial

All patients will receive tumor imaging (CT or MRI) 12 weeks after completion of radiotherapy and panendoscopy with biopsy.

Spots Global Cancer Trial Database for durvalumab + tremelimumab + rt