Dual Inhibition of EGFR With Afatinib and Cetuximab in the Treatment of Advanced Squamous Cell Cancers of the Head and Neck

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02979977
Recruitment Status : Recruiting
First Posted : December 2, 2016
Last Update Posted : August 15, 2018
National Comprehensive Cancer Network
Boehringer Ingelheim
Information provided by (Responsible Party):
Yale University

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.

Condition or disease Intervention/treatment Phase
Squamous Cell Cancers of the Head and Neck Drug: cetuximab Drug: afatinib Phase 2

Detailed Description:
Patients with recurrent/metastatic squamous cell carcinoma of the head and neck, who are previously treated with a platinum based regimen or with an immune checkpoint inhibitor will be eligible for participation on the study. After a baseline evaluation and biopsy, they will be treated with weekly IV cetuximab and daily oral afatinib. Biopsy will be repeated where feasible after 4 weeks 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 1 despite appropriate supportive care.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 24, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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 40 mg per day and weekly IV cetuximab.
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. Doses will be administered on the same day of each week (+/- 1 day).
Other Name: Erbitux

Drug: afatinib
Patients will take a single oral dose of afatinib each day at a dose of 40 mg. Afatinib dose will not be escalated beyond the 40 mg daily oral dose; dose reductions of afatinib can occur to manage treatment related adverse events.

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Duration of response in weeks [ Time Frame: 1 year follow-up ]
  4. 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 Outcome Measures:
  1. 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

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
  • 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 for no more than 9 doses in combination with radiation therapy or chemoradiation therapy for initial treatment of locally advanced disease.
  • Measurable disease based on RECIST v 1.1.
  • ECOG performance status ≤2
  • Adequate organ function, defined as all of the following:
  • Hemoglobin ≥ 9 g/dl.
  • Absolute neutrophil count (ANC) ≥1500 / mm3. (ANC >1000/mm3 may be considered in special circumstances such as benign cyclical neutropenia as judged by the investigator and in discussion with the sponsor).
  • 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).
  • Recovered from any previous therapy related toxicity to ≤Grade 1 or baseline at study entry (except for stable sensory neuropathy ≤Grade 2 and alopecia).
  • 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 4 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.
  • Major surgery within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study.
  • Known hypersensitivity to afatinib or its excipients
  • History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure NYHA classification of ≥ 3, unstable angina or poorly controlled arrhythmia as determined by the investigator. Myocardial infarction within 6 months.
  • 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 that result in a low failure rate of less than 1% per year when used consistently and correctly 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.
  • Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 2 years and is considered to be cured.
  • Requiring treatment with any of the prohibited concomitant medications that cannot be stopped for the duration of trial participation.
  • Known pre-existing interstitial lung disease.
  • Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (e.g. Crohn's disease, ulcerative colitis, chronic diarrhea, malabsorption).
  • Active hepatitis B infection (defined as presence of HepB sAg and/ or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier.
  • Patients with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids, anti-convulsants or have been on stable dose of corticosteroids for at least 4 weeks before starting study treatment. Any symptoms attributed to brain metastases must be stable for at least 4 weeks before starting study treatment.
  • Leptomeningeal carcinomatosis, diagnosed on cytology or appropriate imaging.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02979977

Contact: Julie Holub 203-737-4784
Contact: Tara McPartland 203-737-7173

United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06520-8028
Contact: Clinical Trials Office    203-785-5702      
Principal Investigator: Aarti Bhatia, MD         
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital Not yet recruiting
Baltimore, Maryland, United States, 21287
Contact: Hyunseok Kang, MD, MPH         
United States, Pennsylvania
Fox Chase Cancer Center Not yet recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Jessica Bauman, MD         
Sponsors and Collaborators
Yale University
National Comprehensive Cancer Network
Boehringer Ingelheim
Principal Investigator: Aarti Bhatia, MD, MPH Yale University

Responsible Party: Yale University Identifier: NCT02979977     History of Changes
Other Study ID Numbers: 1608018260
First Posted: December 2, 2016    Key Record Dates
Last Update Posted: August 15, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Antineoplastic Agents