Ignite Creation Date:
2024-05-06 @ 12:31 AM
Last Modification Date:
2024-10-26 @ 10:51 AM
Study NCT ID:
NCT01592721
Status:
COMPLETED
Last Update Posted:
2022-09-21
First Post:
2012-04-26
Brief Title:
Radiation and Cetuximab Plus Intratumoral EGFR Antisense DNA in Locally Advanced Head and Neck Squamous Cell Carcinoma
Sponsor:
The University of Texas Health Science Center at San Antonio
Organization:
The University of Texas Health Science Center at San Antonio
Study Overview
Official Title:
Safety and Efficacy of Radiation and Cetuximab Plus Intratumoral EGFR Antisense DNA in Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma
Status:
COMPLETED
Status Verified Date:
2022-08
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:
The incorporation of novel targeted therapies to radiation therapy is of particular interest in head and neck cancer and may improve efficacy without significantly increasing toxicity The investigators hypothesize that the addition of a second EGFR-targeted agent that inhibits EGFR at the intracellular level will improve the antitumor effect of standard radiation and cetuximab The goal of this study is to evaluate the safety efficacy and the biologic effects in patients with locally advanced SCCHN of an antisense gene targeting the EGFR in combination with standard therapy with radiation and cetuximab
Detailed Description:
The Epidermal Growth Factor Receptor EGFR is highly expressed in SCCHN and its overexpression is associated with poor patient outcome EGFR is a promising target of anticancer therapy The investigators have developed EGFR antisense DNA as a safe and potentially efficacious treatment for SCCHN as shown in a previous phase I study conducted at the University of Pittsburgh Cetuximab Erbitux or C225 is a chimerized EGFR monoclonal antibody that has produced positive results in a phase III trial in SCCHN when added to radiation therapy and was approved by the FDA for the treatment of locally advanced SCCHN Radiation plus cetuximab is considered a standard treatment especially for patients who are not good candidates for chemotherapy In the current study the investigators plan to evaluate the addition of intratumoral EGFR antisense DNA EGFR AS to standard radiation with concurrent cetuximab in patients
Objectives
To evaluate the safety of the combination of intratumoral EGFS AS DNA with standard cetuximab and radiation
To evaluate the locoregional progression-free survival in selected patients with locally advanced SCCHN treated with intratumoral EGFR AS DNA combined with standard radiation plus cetuximab
To evaluate other efficacy parameters including the objective response rate distant control and overall progression-free survival and overall survival
To determine the effect of EGFR antisense therapy on EGFR-related biomarkers The investigators will use reverse phase protein microarrays RPPA and immunohistochemical IHC analysis of tissue microarrays TMA on baseline and post-treatment tumor tissue to determine the expression level and modulation of a panel of EGFR and EGFR-pathway related biomarkers including but not necessarily limited to EGFR pEGFR Src pMAPK STAT3 pSTAT3 pSTAT5 pSTAT1 pAKT p38 p21 p27 PARP E-cadherin p-ErbB3 and Ki67
To examine the transfection of the EGFR antisense gene therapy in vivo
Subject population
The investigators will enroll patients with SCCHN who are suitable for intratumoral injections of EGFR antisense
Treatment plan
EGFR AS will be administered by direct intratumoral injection using direct visualization endoscopy or imaging-guidance ultrasound as clinically determined see protocol Patients will receive a total of up to 4 weekly intratumoral injections of EGFR antisense or less if there is no identifiable tumor starting 2 weeks prior to radiation study schema in protocol Patients will receive standard radiation 70 Gy200 cGydaily 5 daysweek with concurrent cetuximab 250 mgm2 after a loading dose of 400 mgm2 2 weeks prior to starting radiation
Statistical Design and Sample Size
The study will be conducted in two-stages In the first stage 11 patients with stage IVA-C or recurrent disease will be evaluated for safety If the regimen is deemed safe a total of 31 patients with stage III or IVA-B previously untreated SCCHN will be enrolled in the second stage of the study
Objectives
To evaluate the safety of the combination of intratumoral EGFS AS DNA with standard cetuximab and radiation
To evaluate the locoregional progression-free survival in selected patients with locally advanced SCCHN treated with intratumoral EGFR AS DNA combined with standard radiation plus cetuximab
To evaluate other efficacy parameters including the objective response rate distant control and overall progression-free survival and overall survival
To determine the effect of EGFR antisense therapy on EGFR-related biomarkers The investigators will use reverse phase protein microarrays RPPA and immunohistochemical IHC analysis of tissue microarrays TMA on baseline and post-treatment tumor tissue to determine the expression level and modulation of a panel of EGFR and EGFR-pathway related biomarkers including but not necessarily limited to EGFR pEGFR Src pMAPK STAT3 pSTAT3 pSTAT5 pSTAT1 pAKT p38 p21 p27 PARP E-cadherin p-ErbB3 and Ki67
To examine the transfection of the EGFR antisense gene therapy in vivo
Subject population
The investigators will enroll patients with SCCHN who are suitable for intratumoral injections of EGFR antisense
Treatment plan
EGFR AS will be administered by direct intratumoral injection using direct visualization endoscopy or imaging-guidance ultrasound as clinically determined see protocol Patients will receive a total of up to 4 weekly intratumoral injections of EGFR antisense or less if there is no identifiable tumor starting 2 weeks prior to radiation study schema in protocol Patients will receive standard radiation 70 Gy200 cGydaily 5 daysweek with concurrent cetuximab 250 mgm2 after a loading dose of 400 mgm2 2 weeks prior to starting radiation
Statistical Design and Sample Size
The study will be conducted in two-stages In the first stage 11 patients with stage IVA-C or recurrent disease will be evaluated for safety If the regimen is deemed safe a total of 31 patients with stage III or IVA-B previously untreated SCCHN will be enrolled in the second stage of the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| HSC20120131H | OTHER | UTHSCSA IRB | None |