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

NCT02979977 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 1608018260
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Squamous Cell Cancers of the Head and Neck

Outcome Measures

Primary Outcomes (1)

• Tumor Shrinkage

  Objective Response Rate (Complete Response + Partial Response), defined by tumor shrinkage (mm), per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. RECIST v1.1 Response Categories are as follows: Complete Response (CR) - all pathological lymph nodes must be \< 10 mm in short axis; Partial Response (PR) - at least a 30% decrease in the sum of diameters of target lesions; Stable Disease (SD) - The cancer has neither clearly improved nor worsened. Progressive Disease (PD) - at least a 20% increase in the sum of diameters of target lesions AND an absolute increase of ≥ 5 mm.

  Disease progression or end of treatment (up to 2 years)

Secondary Outcomes (4)

• Progression-free Survival in Months

  1 year follow-up

• Overall Survival in Months

  1 year follow-up

• Duration of Response in Weeks

  Up to 6 years

• Toxicity Assessed With National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

  Up to 2.5 years

Other Outcomes (1)

• Exploratory Biomarker Analysis

  Up to 2 years

Study Arms (1)

All subjects

EXPERIMENTAL

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.

Drug: cetuximab; Drug: afatinib

Interventions

cetuximab DRUG

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).

Also known as: Erbitux

All subjects

afatinib DRUG

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.

Also known as: GIOTRIF or GILOTRIF

All subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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. Cetuximab is permitted if used for locally advanced disease, as long as no disease progression within 6 months. Cetuximab use is not permitted for recurrent/metastatic disease
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: collaborator
• Yale University: lead
• National Comprehensive Cancer Network: collaborator

Study Sites (1)

Yale Cancer Center

New Haven, Connecticut, 06520-8028, United States

Location

MeSH Terms

Interventions

Cetuximab; Afatinib

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Aarti Bhatia, MD, MPH, Associate Professor of Medicine (Medical Oncology)
• Organization: Yale University School of Medicine

aarti.bhatia@yale.edu

(203) 200-4622

Study Officials

• Aarti Bhatia, MD, MPH

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 2, 2016
• Study Start: March 24, 2017
• Primary Completion: January 18, 2025
• Study Completion: January 18, 2026
• Last Updated: February 4, 2026
• Results First Posted: February 4, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)