Trials / Recruiting

RecruitingNCT04754321

Combining Immunotherapy Salvage Surgery & IORT Tx Persistent/Recurrent Head & Neck Cancer

HNSALV Trial: Combining Immunotherapy With Salvage Surgery and IORT for Treatment of Persistent/Recurrent Head and Neck Cancers

Status: Recruiting
Phase: Phase 1
Study type: Interventional
Enrollment: 45 (estimated)

Sponsor: Ohio State University Comprehensive Cancer Center · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase I trial is to find out the possible side effects of pembrolizumab and radiation therapy before and during surgery in treating patients with head and neck squamous cell cancer that remains despite treatment (persistent) or has come back (recurrent). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays or protons to kill tumor cells and shrink tumors. Giving pembrolizumab and radiation therapy before and during surgery may kill more tumor cells.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the potential toxicity of immunotherapy and preoperative radiation combined with intra-operative radiation in patients with recurrent or persistent head and neck squamous cell carcinoma (HNSCC). SECONDARY OBJECTIVES: I. To evaluate the clinical efficacy, measured as a locoregional control rate (LCR) and progression-free survival (PFS), of immunotherapy and preoperative radiation combined with intra-operative radiation in patients with recurrent or persistent HNSCC. II. To evaluate the pre-operative radiation dose effect (0 Gy, 2 Gy X 2, 8 Gy X 2) on anti-tumor immune response in the setting of immunotherapy in patients with recurrent or persistent HNSCC. III. To evaluate the radiation dose effect (0 Gy, 2 Gy X 2, 8 Gy X 2) on the expression of the deoxyribonucleic acid (DNA) exonuclease Trex1. IV. To compare the overall survival (OS) of pembrolizumab and pre and post-operative external beam radiation therapy (EBRT) plus intraoperative radiation therapy (IORT) in subjects with recurrent or persistent HNSCC. V. To assess the overall safety and tolerability of pre-operative pembrolizumab and pre-operative EBRT and IORT plus post-operative pembrolizumab versus pre-operative pembrolizumab plus IORT and post-operative pembrolizumab in subjects with with recurrent or persistent HNSCC. VI. To evaluate whether PD-L1 expression is a predictive biomarker for LCR and PFS. VII. To evaluate whether TNF-alpha expression is a predictive biomarker for LCR and PFS. VIII. To evaluate whether NFkappaB expression is a predictive biomarker for LCR and PFS. IX. To evaluate whether tumor mutational burden is predictive of immunotherapy response. X. To evaluate the Health Related Quality of Life (HRQoL) as assessed by European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) and QLQ-HN35. EXPLORATORY OBJECTIVES: I. To evaluate associations between gene expression status of tumor samples and clinical efficacy (LRC, PFS and overall survival \[OS\]). II. To evaluate whether mutational burden is a predictive biomarker for LCR and PFS. III. To explore potential biomarkers associated with clinical efficacy (LRC, PFS, and OS) by analyzing circulating tumor DNA quantitative load with polymerase chain reaction (PCR), chemokines/cytokines and immune cells (e.g. CD8+ T cells, regulatory T cells \[Tregs\], myeloid derived suppressor cells \[MDSCs\]) with FACS in blood, tumor tissue and correlating those with clinical outcomes. OUTLINE: Patients are randomized to 1 of 3 arms. ARM A: Patients receive pembrolizumab intravenously (IV) on day 1 of week 1, and undergo salvage surgery during week 4. Beginning week 8, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo intraoperative radiation therapy (IORT) for 1 fraction during week 9. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab. ARM B: Patients receive pembrolizumab IV on day 1 of week 1, and undergo low dose EBRT for 2 fractions on 2 consecutive days during week 4. Patients also undergo salvage surgery during week 8. Beginning week 11, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 11. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab. ARM C: Patients receive pembrolizumab IV on day 1 of week 1, and undergo high dose EBRT for 2 fractions on 2 consecutive days during week 4. Patients also undergo salvage surgery during week 8. Beginning week 11, patients receive pembrolizumab IV every 3 weeks for up to 18 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo IORT for 1 fraction during week 11. Treatment with pembrolizumab may continue beyond initial progression per investigator-assessed clinical benefit and if the patient is tolerating pembrolizumab. After completion of study treatment, patients are followed up at 90 and 180 days, then every 90 weeks for 24 months, and then every 6 months up to year 5.

Conditions

Interventions

Type	Name	Description
RADIATION	External Beam Radiation Therapy	Undergo EBRT
RADIATION	Intraoperative Radiation Therapy	Undergo IORT
BIOLOGICAL	Pembrolizumab	Given IV
OTHER	Quality-of-Life Assessment	Ancillary studies
PROCEDURE	Salvage Surgery	Undergo salvage surgery

Timeline

Start date: 2022-05-12
Primary completion: 2026-12-31
Completion: 2026-12-31
First posted: 2021-02-15
Last updated: 2026-02-02

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT04754321. Inclusion in this directory is not an endorsement.