sEphB4-HSA With RT+Chemo or Cetux in Patients With Intermediate to High Risk LAHNSCC

NCT04091867 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 16-2575.ccNCI-2019-06321
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Squamous Cell Carcinoma of Head and Neck

Outcome Measures

Primary Outcomes (1)

• 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).

  13 weeks

Secondary Outcomes (4)

• 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

  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

  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

  13 weeks

• Overall Survival

  13 weeks

Other Outcomes (6)

• 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

  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

  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

  13 weeks

Study Arms (1)

sEphB4-HSA with CRT

EXPERIMENTAL

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

Interventions

sEphB4-HSA with chemotherapy DRUG

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).

sEphB4-HSA with CRT

Cetuximab DRUG

Loading dose 400 mg/m2 on D9 Concurrent dose 250mg/m2 weekly D15± 3 day window

sEphB4-HSA with CRT

Radiation Therapy RADIATION

6930 cGy IMRT starting D15-D18

sEphB4-HSA with CRT

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision to sign and date the consent form.
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Patients must be willing to consent for two mandatory biopsies to be collected at baseline and again one week after the loading dose of sEphB4-HSA. A third optional biopsy will be collected if feasible 5-10 days after initiation of radiation treatment.
• Be a male or female aged 18-100.
• Pathologically confirmed (from the primary lesion and/or regional lymph nodes) squamous cell carcinoma of the oropharynx, hypopharynx, oral cavity, unknown primary, or larynx.
• High risk, locally advanced HNSCC which may include any of the following by AJCC 8th Edition:
• Stage III Hypopharyngeal Carcinoma AJCC v8
• Stage III Laryngeal Cancer AJCC v8
• Stage III Lip and Oral Cavity Cancer AJCC v8
• Stage III Oropharyngeal (p16-Negative) Carcinoma AJCC v8 or Stage III Oropharyngeal (p16-positive) Carcinoma ≥ 10 pack-years history of smoking
• Stage IVA Hypopharyngeal Carcinoma AJCC v8
• Stage IVA Laryngeal Cancer AJCC v8
• Stage IVA Lip and Oral Cavity Cancer AJCC v8
• Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8 or Stage IVA Oropharyngeal (p16-positive) Carcinoma ≥ 10 pack-years history of smoking
• Stage IVB Hypopharyngeal Carcinoma AJCC v8

You may not qualify if:

• Pregnant, attempting to conceive, lactating, or declining to use appropriate contraception for duration of study.
• Hypertension that is uncontrolled (requiring 3+ antihypertensive medications to control).
• Hypertension at screening (SBP ≥140mmHg or DBP ≥90mmHg, corresponding to Stage 2 according to JNC 7).
• Prior history of allergic or infusion reaction to cetuximab or sEphB4.
• Febrile illness within 7 days prior to enrollment.
• Concomitant use of EGFR-directed therapies (besides cetuximab given as part of this trial), including erlotinib, gefitinib.
• Major surgery (excluding tumor biopsy) within 4 weeks prior to start of study treatment.
• Prior unrelated malignancy requiring current active treatment within 3 years prior to enrollment with exceptions of cervical carcinoma in situ, basal cell carcinoma of skin, resected T1-T2N0M0 differentiated thyroid cancers, Ta bladder cancer, prostatic adenocarcinoma of low or intermediate risk (per NCCN criteria).
• Treatment with another investigational drug or other intervention within 30 days of treatment start.
• Resectable oral cavity primary site
• p16-positive carcinoma of the oropharynx or unknown primary that are T0-3, N0-1 (AJCC 8th Edition) AND ≤ 10 pack-year smoking history
• Stage IVC (M1) disease per AJCC 8th edition.
• Prior receipt of systemic chemotherapy for the study cancer (including "induction" or "neoadjuvant" chemotherapy) within 60 days of diagnosis; prior chemotherapy for a different cancer diagnosis is allowed.
• Any severe, active comorbidity, defined as follows:
• Cardiovascular disease or cerebrovascular disease, for example cerebrovascular accidents or myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or with the potential to interfere with protocol treatment;

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Vasgene Therapeutics, Inc: collaborator

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Drug Therapy; Cetuximab; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will be enrolled using a 3+3 model. All patients will receive a fixed loading dose of 10 mg/kg to be followed by the assigned dose level during the concurrent phase. The 3+3 design model applies only to the concurrent phase. An expansion cohort of 6 patients will be added for testing biological endpoints.

Study Record Dates

• First Submitted: August 9, 2019
• First Posted: September 17, 2019
• Study Start: January 6, 2020
• Primary Completion: May 14, 2021
• Study Completion: October 25, 2022
• Last Updated: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)