Ignite Creation Date:
2025-12-24 @ 6:37 PM
Ignite Modification Date:
2025-12-30 @ 4:06 AM
Study NCT ID:
NCT03426657
Status:
COMPLETED
Last Update Posted:
2024-04-11
First Post:
2018-01-24
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Radiotherapy With Double Checkpoint Blockade of Locally Advanced HNSCC
Sponsor:
University of Erlangen-Nürnberg Medical School
Organization:
Study Overview
Official Title:
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)
Status:
COMPLETED
Status Verified Date:
2023-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
First-line treatment of locally advanced HNSCC with double checkpoint blockade and radiotherapy dependent on intratumoral CD8+ T cell Infiltration.
Detailed Description:
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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: