NCT03317327

REirradiation and Programmed Cell Death Protein 1 (PD-1) Blockade On Recurrent Squamous Cell Head and Neck Tumors

REPORT; REirradiation and PD-1 Blockade On Recurrent Squamous Cell Head and Neck Tumors

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Oslo University Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Each subject will participate in the trial until death, drop out, or loss-to follow-up from the time the subject signs the Informed Consent Form (ICF) through the final contact. After a screening phase of up to 28 days, each eligible subject will receive nivolumab. Two weeks after start of nivolumab the patients will receive radiotherapy (RT) to a total dose of 60 Gy, given as 1.5 Gy fractions twice daily for a total period of 4 weeks. Treatment with nivolumab will continue until disease progression, unacceptable adverse event(s), intercurrent illness that prevents further administration of treatment, Investigator's decision to withdraw the subject, noncompliance with trial treatment or procedures requirements, subject receives nivolumab for 12 months, pregnancy, or administrative reasons. After the end of treatment, each subject will be followed for 30 days for adverse event monitoring serious adverse events (SAEs) will be collected for 90 days after the end of treatment. Patients without disease progression will have follow-up visits for 4 years after end of study therapy.

Detailed description

In this study, the aim is to release the brake on the immune response by use of nivolumab, an inhibitory antibody against Programmed cell death protein 1 (PD-1). Nivolumab has shown efficacy and mild toxicity when given as monotherapy for HNSCC at a dose of 3.0 mg/kg every 2 weeks, which is the target dose in the present trial. Radiotherapy is a powerful inducer of inflammation, and the expression of Programmed death-ligand 1 (PD-L1) is known to be enhanced by inflammatory cytokines, including interferon-gamma (IFNg). Experimental evidence from mice models have shown that radiotherapy induces increased PD-L1 expression in tumor tissue. Moreover, there is evidence suggesting that HNSCC with T-cell infiltration is more sensitive to radiotherapy. There is thus a strong rationale for combing PD-1 inhibitors with radiotherapy. However, this potential remains largely unexplored in humans. The investigators consider that head-and-neck cancer is a particularly attractive entity for investigating this therapeutic combination, because of i) the high radiosensitivity of this cancer form ii) the clinical efficacy of Programmed cell death protein 1 (PD-1) inhibitors as monotherapy in early clinical trials iii) the availability of tumor biopsies for translational/biomarker research.The RT given in the present study gives considerable side effects, related to inflammation that may be enhanced by Programmed cell death protein 1 (PD-1) blockade.

Conditions

• Head and Neck Squamous Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Nivolumab	Nivolumab is a humanized antibody used in cancer immunotherapy.
RADIATION	Radiotherapy (RT)	Radiotherapy (RT) will be given to a total dose of 60 Gy (1,5 Gy fractions twice daily) for a total period of 4 weeks

Timeline

• Start date: 2017-09-09
• Primary completion: 2022-11-28
• Completion: 2022-11-28
• First posted: 2017-10-23
• Last updated: 2025-06-03

Locations

1 site across 1 country: Norway