A Phase 1 interventional study of sEphB4-HSA with chemotherapy and Cetuximab in Squamous Cell Carcinoma of Head and Neck, sponsored by University of Colorado, Denver. Completed at 1 site in United States. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2025-02-24.
Sponsored by University of Colorado, Denver · Phase 1, Interventional, and Treatment
This is a Phase I dose-escalation study of sEphB4-HSA in combination with chemotherapy, cetuximab and radiotherapy (RT). The purpose is to estimate the maximum tolerated dose (MTD) that can be administered concurrently with Cetuximab and radiation in patients with locally advanced, Stage III or IV A-B squamous cell carcinomas of the head or neck with a history of at least ten pack-years of smoking.
RT combined with the EGFR-targeted agent cetuximab represents a valuable alternative to platinum-based CRT and is FDA-approved for initial treatment of LAHNSCC, but outcomes remain unfavorable. Recently, EphB4 has emerged as another rational target. While minimally expressed in normal tissue, it is highly expressed in LAHNSCC and has been implicated in resistance to both EGFR-targeted therapy and to RT. Suppression of EphB4 in the preclinical setting has enhanced tumor death and enhanced radiosensitivity. The novel agent sEphB4-HSA is a fusion protein that binds the ligand for EphB4 and leads to inhibition of tumor proliferation and angiogenesis. It was well-tolerated as monotherapy in a phase I trial but has yet to be explored in combination with radiotherapy or EGFR-directed treatments. A combined modality approach adding sEphB4-HSA to standard-of-care RT plus cetuximab represents a rational, targeted approach for investigation in patients with high risk LAHNSS p16-negative or any patient with heavy smoking histories. Moreover, a short window period of sEphB4-HSA monotherapy between baseline biopsy and repeat biopsy prior to initiation of cetuximab with RT will both minimize potential treatment delay and allow for the identification of potential biomarkers of response to sEphB4-HSA. Finally, a third optional biopsy, to be done if feasible after initiation of cetuximab-radiation, will allow us to identify radiosensitization markers and potential markers for treatment de-escalation. MTD.
6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.
This study's enrollment of 3 is below the median of 45 across 5,170 interventional studies indexed under Carcinoma.
Browse Carcinoma studies →University of Colorado, Denver is the lead sponsor of 1,499 studies on the registry; 315 are open to participants now.
Of its 139 completed or terminated interventional studies of FDA-regulated products, 89 (64%) have results posted.
Counted across the registry records on this site, refreshed daily.
High risk, locally advanced HNSCC which may include any of the following by AJCC 8th Edition:
Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
Agreement to exercise appropriate use of contraception, as indicated.
Pretreatment imaging to include the following within 28 days of treatment initiation:
CT Neck (with contrast unless contraindicated) with CT chest OR PET-CT. MRI of the neck with contrast (unless contraindicated) can replace CT neck.
N.B.: a CT Neck performed for radiation planning and read by a radiologist may serve as appropriate staging and planning tools.
Exclusion Criteria:
Any severe, active comorbidity, defined as follows:
sEphB4-HSA: Loading dose at fixed dose of 10mg/Kg per below schema on D1 Concurrent dose per below schema D15-43 and given on an every other week basis Concurrent chemotherapy drug (either cisplatin or carboplatin): Per treating physician discretion, and treatment plan is based per NCCN guidelines. These can be administered in tri-weekly or weekly doses during the radiation period. The participant will receive the first infusion on Day 15 (+/- 3 days). Cetuximab: Loading dose 400 mg/m2 on D9 Concurrent dose 250mg/m2 weekly D15± 3 day window RT: 6930 cGy IMRT starting D15-D18
Drug: sEphB4-HSA with chemotherapy · Drug: Cetuximab · Radiation: Radiation Therapy
sEphB4-HSA is a fusion protein combining the soluble extracellular EphB4 domain with albumin that targets the ephrin B2 receptor, which is thought to mediate resistance to EGFR-targeted therapy, and acts as a radiosensitizer by enhancing DNA damage and promoting apoptosis. Concurrent chemotherapy drug (either cisplatin or carboplatin): Per treating physician discretion, and treatment plan is based per NCCN guidelines. These can be administered in tri-weekly or weekly doses during the radiation period. The participant will receive the first infusion on Day 15 (+/- 3 days).
Loading dose 400 mg/m2 on D9 Concurrent dose 250mg/m2 weekly D15± 3 day window
6930 cGy IMRT starting D15-D18
The primary endpoint is whether a dose-limiting toxicity (DLT) occurs
Severe cetuximab-associated rash is defined as per Lacouture 2010 criteria69, namely \> 20 papules or pustules OR \> 5 areas of erythema or edema \< 1 cm (this is grade 3A) or \> 20 papules/pustules OR \> 5 areas of erythema or edema \< 1 cm AND pain, pruritus, or effect on emotions or functioning (this is a commonly used criteria for grading of rash specifically related to EGFR inhibitors, such as cetuximab).
Time frame: 13 weeks
To assess the effect of adding sEphB4-HSA to radiation and cetuximab in newly-diagnosed EGFR-expressing LAHNSCC and heavy smoking histories on Locoregional disease
Tumor response will be assessed in participants with measurable disease at start of therapy by measuring change in size (and/or FDG avidity) on CT (and/or PET/CT). LRC will be calculated as the time from completion of locoregional therapy until disease recurrence at the primary site or in the neck.
Time frame: 13 weeks
To assess the effect of adding sEphB4-HSA to radiation and cetuximab in newly-diagnosed EGFR-expressing LAHNSCC and heavy smoking histories on Distant Control
DC will be calculated as the time from completion of locoregional therapy until disease recurrence at a site other than the primary site or neck.
Time frame: 13 weeks
To assess the effect of adding sEphB4-HSA to radiation and cetuximab in newly-diagnosed EGFR-expressing LAHNSCC and heavy smoking histories on Disease Free Survival
DFS will be calculated as the time from completion of locoregional therapy until either disease recurrence at any site or until death.
Time frame: 13 weeks
Overall Survival
OS will be calculated as the time from diagnosis of LAHNSCC to death
Time frame: 13 weeks
To assess target expression analysis, genomic, and immune analysis in tumor and blood samples obtained at baseline, after loading dose of s-EphB4-HSA, during CRT and at follow-up
To establish a gene signature panel on biopsy samples that can assess the response to sEphB4HSA
Time frame: 13 weeks
To assess target expression analysis, genomic, and immune analysis in tumor and blood samples obtained at baseline, after loading dose of s-EphB4-HSA, during CRT and at follow-up
Evaluate immune infiltration by multiplex immunofluorescence
Time frame: 13 weeks
To assess target expression analysis, genomic, and immune analysis in tumor and blood samples obtained at baseline, after loading dose of s-EphB4-HSA, during CRT and at follow-up
Blood samples to evaluate biomarkers of immune response including mass cytometry on circulating peripheral blood, and analysis of plasma cytokine, cleaved soluble ephrin-B2 as well as for evaluation of circulating auto-antibodies. Blood will be collected at baseline (before the administration of sEphB4) and after administration of sEphB4, as well as on day 22 of treatment and at the end of treatment at the follow-up visit. Cytokine mesoscale assays as well as Elisas will be used
Time frame: 13 weeks
To assess target expression analysis, genomic, and immune analysis in tumor and blood samples obtained at baseline, after loading dose of s-EphB4-HSA, during CRT and at follow-up
Tumor or nodal tissue taken at the time of initial biopsy and after sEphB4 HSA and will be profiled for whole gene and transcriptome sequencing of FFPE tissue, tumor infiltrating lymphocytes; activation markers and antigen specific TCR utilization/diversity.
Time frame: 13 weeks
To assess target expression analysis, genomic, and immune analysis in tumor and blood samples obtained at baseline, after loading dose of s-EphB4-HSA, during CRT and at follow-up
On long-term follow-up (6 months), tumor antigen specific T lymphocyte memory populations will be monitored for representation and robustness in in-vitro stimulation assays as potential biomarker of continued anti-tumor activity. PBMCs will be separately collected for this purpose.
Time frame: 13 weeks
To assess target expression analysis, genomic, and immune analysis in tumor and blood samples obtained at baseline, after loading dose of s-EphB4-HSA, during CRT and at follow-up
Circulating tumor DNA (ctDNA) will also be collected.
Time frame: 13 weeks
Plan to share: No
No publications or documents are linked to this record.
This study is completed, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
University of Colorado, Denver