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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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ClinicalTrials.gov Identifier: NCT02979977
Recruitment Status : Recruiting
First Posted : December 2, 2016
Last Update Posted : May 6, 2021
Sponsor:
Collaborators:
National Comprehensive Cancer Network
Boehringer Ingelheim
Information provided by (Responsible Party):
Yale University

Tracking Information
First Submitted Date  ICMJE November 29, 2016
First Posted Date  ICMJE December 2, 2016
Last Update Posted Date May 6, 2021
Actual Study Start Date  ICMJE March 24, 2017
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 29, 2016)
Tumor shrinkage [ Time Frame: Disease progression or end of treatment (up to 2 years) ]
Objective Response Rate (Complete Response + Partial Response), defined by tumor shrinkage (mm), per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2016)
  • Progression-free survival in weeks [ Time Frame: 1 year follow-up ]
    We will use Kaplan-Meier survival analysis to estimate the median PFS in the cohort.
  • Overall survival in months [ Time Frame: 1 year follow-up ]
    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 [ Time Frame: 1 year follow-up ]
  • Toxicity assessed with National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 2.5 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 29, 2016)
Exploratory biomarker analysis [ Time Frame: Up to 2 years ]
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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Dual Inhibition of EGFR With Afatinib and Cetuximab in the Treatment of Advanced Squamous Cell Cancers of the Head and Neck
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Squamous Cell Cancers of the Head and Neck
Intervention  ICMJE
  • Drug: cetuximab
    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).
    Other Name: Erbitux
  • Drug: afatinib
    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.
    Other Name: GIOTRIF or GILOTRIF
Study Arms  ICMJE Experimental: All subjects
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.
Interventions:
  • Drug: cetuximab
  • Drug: afatinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 29, 2016)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alexander Hoslet, CCRP 203-785-5573 Alexander.hoslet@yale.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02979977
Other Study ID Numbers  ICMJE 1608018260
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE
  • National Comprehensive Cancer Network
  • Boehringer Ingelheim
Investigators  ICMJE
Principal Investigator: Aarti Bhatia, MD, MPH Yale University
PRS Account Yale University
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP