Cetuximab in Head and Neck Cancer Patients
|ClinicalTrials.gov Identifier: NCT03769311|
Recruitment Status : Suspended (COVID-19)
First Posted : December 7, 2018
Last Update Posted : March 25, 2020
|Condition or disease||Intervention/treatment||Phase|
|Head and Neck Cancer Squamous Cell Carcinoma||Drug: Cetuximab||Phase 2|
This is a window of opportunity trial evaluating the hypothesis that AXL levels correlate with clinical response to cetuximab in head and neck patients. Patients with head and neck squamous cell carcinoma who are scheduled to undergo surgical resection of their tumor and are candidates for cetuximab chemotherapy are eligible to participate.
1. To test the hypothesis that low AXL correlates with clinical response to cetuximab in head and neck cancer patients
1. To further describe the safety of pre-operative administration of cetuximab
- To correlate AXL expression with change in Ki67 following cetuximab in Head and Neck Cancer (HNC) patients
- To examine other putative markers of cetuximab sensitivity such as HER3 and change in circulating tumor cells
- To establish the first panel of patient-derived xenografts from patients with known sensitivity or resistance to cetuximab
Following informed consent, tumor tissue from the research biopsy and a blood draw for circulating tumor cells will be obtained. The participant will then receive two weekly doses of pre-operative cetuximab during the interval between diagnostic biopsy and surgery (~14 days), ensuring that no delay in standard of care (SOC) will occur.
For dose #1, participants will receive cetuximab 400 mg/m2 via intravenous infusion over 2 hours (maximum infusion rate 10 mg/min) as per the standard of care loading regimen for cetuximab monotherapy.
For dose #2, participants will receive cetuximab 250 mg/m2 via intravenous infusion over 1 hour (maximum infusion rate 10 mg/min) as per the standard of care dosing regimen for cetuximab monotherapy.
At the time of surgery, another blood draw will be obtained for analysis of circulating tumor cells, and a portion of the resected tumor will be obtained for study analysis.
Correlative studies will include the measurement of proteins hypothesized to be involved in cetuximab resistance such as AXL, Ki67, EGFR, and HER3 expression from both the biopsy and the surgical specimen. Blood will be analyzed for correlative analysis of circulating tumor cells. Tissue from the research biopsy will be utilized for participant-derived xenograft (PDX) development.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Single site, open label, window of opportunity study|
|Masking:||None (Open Label)|
|Official Title:||A Window of Opportunity Trial of Cetuximab in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC)|
|Actual Study Start Date :||May 8, 2019|
|Estimated Primary Completion Date :||March 2022|
|Estimated Study Completion Date :||March 2023|
Experimental: Pre-Operative Cetuximab Therapy
Two weekly doses of pre-operative cetuximab during the interval between diagnostic HNSCC biopsy and surgery (~14 days), ensuring that no delay in standard of care (SOC) will occur. For dose #1, participants will receive cetuximab 400 mg/m2 via intravenous infusion over 2 hours (maximum infusion rate 10 mg/min) as per the standard of care loading regimen for cetuximab monotherapy. For dose #2, participants will receive cetuximab 250 mg/m2 via intravenous infusion over 1 hour (maximum infusion rate 10 mg/min) as per the standard of care dosing regimen for cetuximab monotherapy.
Monoclonal antibody against epidermal growth factor receptor (EGFR)
- Change in Tumor Size [ Time Frame: up to 42 days ]The tumor size (via clinical measurements) will be measured from the time of diagnosis (pre-CTX) to after treatment with 2 doses of cetuximab and within 48 hours prior to surgery (post-CTX). Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Committee criteria will be used to define clinical response prior to surgery.
- Objective Tumor Response Rate - AXL expression [ Time Frame: up to 42 days ]The levels of AXL expression (low vs high) at the time of diagnosis (pre-CTX) will measured and compared to change in the tumor size as reported in Primary Outcome Measure 1. The relationship between AXL expression as a continuous variable with clinical response will be analyzed using the Wilcoxon rank sum test.
- Rate of Hospital Re-admission for CTX-related Complications [ Time Frame: up to 42 days from on study ]Hospital re-admission for wound healing, surgical complications, or infection that occur within 28 days after surgery will be categorized as definitely related, probably related, possibility related, unlikely related, or unrelated to cetuximab administration and will be reported as a proportion including an exact 95% confidence interval.
- Change in Ki67 from Pre- vs Post-CTX Treated Tumors [ Time Frame: up to 30 months ]Summary statistics of the change in Ki67 (ΔKi67), as established by the surgical specimen, will be reported for the response to cetuximab endpoint.
- Correlation of Measures of Putative Markers of CTX Sensitivity [ Time Frame: up to 30 months ]Markers include: protein, RNA, circulating tumor cells with CTX response, measured by Ki67. Correlation between ΔKi67 and putative biomarkers will be analyzed as a continuous variable and will be tested using Pearson's correlation coefficient. Correlation between two biomarkers such as AXL and HER3 expression as continuous variables will be investigated using Pearson's correlation coefficient. Summary statistics will be used to report circulating tumor cells at each time point and the changes between time points. The association of change in circulating tumor cells with ΔKi67 (early response) will be explored graphically and with Pearson's correlation coefficient.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03769311
|United States, Wisconsin|
|University of Wisconsin Carbone Cancer Center|
|Madison, Wisconsin, United States, 53792|
|Principal Investigator:||Justine Bruce||University of Wisconsin, Madison|