Dual Inhibition of EGFR With Afatinib and Cetuximab in the Treatment of Advanced Squamous Cell Cancers of the Head and Neck
Primary Purpose
Squamous Cell Cancers of the Head and Neck
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
cetuximab
afatinib
Sponsored by
About this trial
This is an interventional treatment trial for Squamous Cell Cancers of the Head and Neck
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed squamous cell carcinoma of the head and neck that is metastatic, recurrent or locally advanced and not treatable with curative intent.
- Previous treatment with a platinum-based regimen or immune checkpoint inhibitor or both.2-week washout period prior to treatment start will be required.
- Patients who have experienced progression of disease within 6 months following completion of a platinum-based chemoradiation in the definitive or adjuvant setting will be permitted.
- Prior cetuximab permitted if it was given as part of multi-modality therapy for initial treatment of locally advanced disease.
- Measurable disease based on RECIST v 1.1. Baseline measurements and evaluations must be obtained within 4 weeks of enrollment. Disease in previously irradiated sites is considered measurable if there has been unequivocal disease progression or biopsy-proven residual carcinoma following radiation therapy.
- ECOG performance status ≤2
- Adequate organ function, defined as all of the following:
- Hemoglobin ≥ 8 g/dl.
- Absolute neutrophil count (ANC) ≥1000 / mm3.
- Platelet count ≥75,000 / mm3.
- Estimated creatinine clearance > 45ml / min.
- Total Bilirubin ≤ 1.5 times upper limit of (institutional/central) normal (Patients with Gilbert's syndrome total bilirubin must be ≤4 times institutional upper limit of normal).
- Aspartate amino transferase (AST) or alanine amino transferase (ALT) ≤ three times the upper limit of (institutional/central) normal (ULN) (if related to liver metastases ≤ five times ULN).
- Ability to understand and the willingness to sign a written informed consent that is consistent with ICH-GCP guidelines.
- Negative urine or serum pregnancy test for women of childbearing potential
Exclusion Criteria:
- Prior erlotinib, gefitinib or lapatinib therapy or prior exposure to any investigational EGFR or panErbB reversible or irreversible inhibitor or any prior panitumumab or investigational EGFR-directed monoclonal antibody.
- Radiotherapy within 2 weeks prior to enrollment. Palliative radiation to target organs may be allowed up to 2 weeks prior to enrollment, as long as there are other target lesions that can be monitored for response to study treatment.
- Known hypersensitivity to afatinib or its excipients
- Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use highly effective methods of birth control prior to study entry, for the duration of study participation and for at least 4 weeks after treatment has ended.
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
- Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug.
- Concomitant malignancies at other sites that are being actively treated with systemic therapy
- Requiring treatment with any of the prohibited concomitant medications that cannot be stopped for the duration of trial participation.
- Clinically significant interstitial lung disease.
- Known history of untreated viral hepatitis or HIV.
- Patients with parenchymal brain metastases are not eligible, unless they have completed local therapy
- Leptomeningeal carcinomatosis
Sites / Locations
- Yale Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
All subjects
Arm Description
Advanced squamous cell carcinoma of the head and neck region, having previously been treated on a platinum based regimen or with an immune checkpoint inhibitor. Subjects will receive Afatinib dose 30 mg per day and weekly/bi-weekly intravenous cetuximab.
Outcomes
Primary Outcome Measures
Tumor shrinkage
Objective Response Rate (Complete Response + Partial Response), defined by tumor shrinkage (mm), per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Secondary Outcome Measures
Progression-free survival in weeks
We will use Kaplan-Meier survival analysis to estimate the median PFS in the cohort.
Overall survival in months
Measured by a monthly phone calls. We will use Kaplan-Meier survival analysis to estimate the median and OS in the cohort.
Duration of response in weeks
Toxicity assessed with National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Full Information
NCT ID
NCT02979977
First Posted
November 29, 2016
Last Updated
October 3, 2023
Sponsor
Yale University
Collaborators
National Comprehensive Cancer Network, Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT02979977
Brief Title
Dual Inhibition of EGFR With Afatinib and Cetuximab in the Treatment of Advanced Squamous Cell Cancers of the Head and Neck
Official Title
Single-Arm Phase II Trial of Dual Inhibition of EGFR With Afatinib and Cetuximab With Correlative Studies in the Treatment of Advanced Squamous Cell Cancers of the Head and Neck
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 24, 2017 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
January 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
Collaborators
National Comprehensive Cancer Network, Boehringer Ingelheim
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a single arm Phase II study for patients with recurrent or metastatic squamous cell carcinoma of the head and neck, who are previously treated with a platinum based regimen or with an immune checkpoint inhibitor. The primary objective is to evaluate the efficacy of the combination of cetuximab and afatinib.
Detailed Description
This study will be a multicenter, single-arm, open-label Phase II trial. Patients with advanced squamous cell carcinoma of the head and neck, who are previously treated with a platinum based regimen or with immune checkpoint inhibitor therapy or both, will be eligible for participation on the study. After a baseline evaluation and biopsy (where feasible), they will be treated with weekly/bi-weekly intravenous cetuximab and daily oral afatinib. Biopsy will be repeated where feasible after 4 weeks (window of +1 week) on therapy and again at disease progression or end of treatment.
Treatment will continue until disease progression or development of Grade 3 or higher drug related toxicities that fail to resolve to Grade 2 despite appropriate supportive care.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Squamous Cell Cancers of the Head and Neck
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
All subjects
Arm Type
Experimental
Arm Description
Advanced squamous cell carcinoma of the head and neck region, having previously been treated on a platinum based regimen or with an immune checkpoint inhibitor. Subjects will receive Afatinib dose 30 mg per day and weekly/bi-weekly intravenous cetuximab.
Intervention Type
Drug
Intervention Name(s)
cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
30-60 minutes after the recommended pre-medications, cetuximab will be administered intravenously at a dose of 400mg/m2 on cycle 1, day 1 of treatment (loading dose) and at a dose of 250mg/m2 every 7 days (+/- 1 day) thereafter. Alternatively, patients can be treated at a dose of 500mg/m2 every 14 days (+/- 2 days).
Intervention Type
Drug
Intervention Name(s)
afatinib
Other Intervention Name(s)
GIOTRIF or GILOTRIF
Intervention Description
Patients will take a single oral dose of afatinib each day at a dose of 30 mg. Afatinib dose will not be escalated beyond the 30 mg daily oral dose; dose reductions of afatinib can occur to manage treatment related adverse events.
Primary Outcome Measure Information:
Title
Tumor shrinkage
Description
Objective Response Rate (Complete Response + Partial Response), defined by tumor shrinkage (mm), per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time Frame
Disease progression or end of treatment (up to 2 years)
Secondary Outcome Measure Information:
Title
Progression-free survival in weeks
Description
We will use Kaplan-Meier survival analysis to estimate the median PFS in the cohort.
Time Frame
1 year follow-up
Title
Overall survival in months
Description
Measured by a monthly phone calls. We will use Kaplan-Meier survival analysis to estimate the median and OS in the cohort.
Time Frame
1 year follow-up
Title
Duration of response in weeks
Time Frame
1 year follow-up
Title
Toxicity assessed with National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame
Up to 2.5 years
Other Pre-specified Outcome Measures:
Title
Exploratory biomarker analysis
Description
Analysis of tumor-tissue from biopsies obtained at baseline, after four weeks of treatment with the combination, and again at disease progression or end of treatment
Time Frame
Up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed squamous cell carcinoma of the head and neck that is metastatic, recurrent or locally advanced and not treatable with curative intent.
Previous treatment with a platinum-based regimen or immune checkpoint inhibitor or both.2-week washout period prior to treatment start will be required.
Patients who have experienced progression of disease within 6 months following completion of a platinum-based chemoradiation in the definitive or adjuvant setting will be permitted.
Prior cetuximab permitted if it was given as part of multi-modality therapy for initial treatment of locally advanced disease.
Measurable disease based on RECIST v 1.1. Baseline measurements and evaluations must be obtained within 4 weeks of enrollment. Disease in previously irradiated sites is considered measurable if there has been unequivocal disease progression or biopsy-proven residual carcinoma following radiation therapy.
ECOG performance status ≤2
Adequate organ function, defined as all of the following:
Hemoglobin ≥ 8 g/dl.
Absolute neutrophil count (ANC) ≥1000 / mm3.
Platelet count ≥75,000 / mm3.
Estimated creatinine clearance > 45ml / min.
Total Bilirubin ≤ 1.5 times upper limit of (institutional/central) normal (Patients with Gilbert's syndrome total bilirubin must be ≤4 times institutional upper limit of normal).
Aspartate amino transferase (AST) or alanine amino transferase (ALT) ≤ three times the upper limit of (institutional/central) normal (ULN) (if related to liver metastases ≤ five times ULN).
Ability to understand and the willingness to sign a written informed consent that is consistent with ICH-GCP guidelines.
Negative urine or serum pregnancy test for women of childbearing potential
Exclusion Criteria:
Prior erlotinib, gefitinib or lapatinib therapy or prior exposure to any investigational EGFR or panErbB reversible or irreversible inhibitor or any prior panitumumab or investigational EGFR-directed monoclonal antibody.
Radiotherapy within 2 weeks prior to enrollment. Palliative radiation to target organs may be allowed up to 2 weeks prior to enrollment, as long as there are other target lesions that can be monitored for response to study treatment.
Known hypersensitivity to afatinib or its excipients
Women of child-bearing potential (WOCBP) and men who are able to father a child, unwilling to be abstinent or use highly effective methods of birth control prior to study entry, for the duration of study participation and for at least 4 weeks after treatment has ended.
Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
Any history of or concomitant condition that, in the opinion of the Investigator, would compromise the patient's ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug.
Concomitant malignancies at other sites that are being actively treated with systemic therapy
Requiring treatment with any of the prohibited concomitant medications that cannot be stopped for the duration of trial participation.
Clinically significant interstitial lung disease.
Known history of untreated viral hepatitis or HIV.
Patients with parenchymal brain metastases are not eligible, unless they have completed local therapy
Leptomeningeal carcinomatosis
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Cindy Voghell
Phone
203-737-4784
Email
cynthia.voghell@yale.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aarti Bhatia, MD, MPH
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520-8028
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Trials Office
Phone
203-785-5702
First Name & Middle Initial & Last Name & Degree
Aarti Bhatia, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Dual Inhibition of EGFR With Afatinib and Cetuximab in the Treatment of Advanced Squamous Cell Cancers of the Head and Neck
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