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Afatinib Dimaleate and Cetuximab as Second-Line Treatment in Treating Patients with Recurrent or Metastatic Head and Neck Squamous Cell Cancer

Trial Status: Active

This phase II trial studies how well afatinib dimaleate and cetuximab work as second-line treatment in treating patients with head and neck squamous cell cancer that has come back or has spread to other parts of the body. Afatinib dimaleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, may interfere with the ability of tumor cells to grow and spread. Giving afatinib dimaleate and cetuximab may work better in treating patients with head and neck squamous cell cancer.

Inclusion Criteria

  • Histologically or cytologically confirmed squamous cell carcinoma of the head and neck that is metastatic or recurrent and not treatable with curative intent
  • Previous disease progression on or intolerance to one line of therapy – either platinum-based or immunotherapy (pembrolizumab or nivolumab); prior chemotherapy in the induction, organ preservation, definitive or adjuvant setting permitted if it was for initial treatment of locally advanced or metastatic disease and completed more than 4 months prior to enrollment on the current study; 2-week washout period prior to treatment start will be required
  • 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 or metastatic disease and completed at least 4 months prior to study enrollment
  • Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version (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
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Hemoglobin >= 9 g/dl
  • Absolute neutrophil count (ANC) >= 1500/mm^3; (ANC > 1000/mm^3 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/mm^3
  • Estimated creatinine clearance > 45 ml/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 International Conference on Harmonization (ICH)-Good Clinical Practice (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
  • Hormonal treatment within 2 weeks prior to start of study treatment (continued use of anti-androgens and/or gonadorelin analogues for treatment of prostate cancer permitted); radiotherapy within 4 weeks prior to enrolment; palliative radiation to target organs may be allowed up to 2 weeks prior to enrolment, 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 New York Heart Association (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 3 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 hepatitis B [Hep B] surface antigen [sAg] and/or Hep B deoxyribonucleic acid [DNA]), active hepatitis C infection (defined as presence of hepatitis C [Hep C] ribonucleic acid [RNA]) and/or known human immunodeficiency virus (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


New Haven
Yale University
Status: ACTIVE
Contact: Aarti Bhatia
Phone: 203-785-2360


Fox Chase Cancer Center
Contact: Aarti Bhatia
Phone: 203-785-2360


I. To determine the response of recurrent or metastatic squamous cell carcinoma of the head and neck region to treatment with a combination of afatinib dimaleate (afatinib) and cetuximab.


I. To determine impact on long-term efficacy outcomes, safety and tolerability of the combination and laboratory correlates for more effective inhibition of epidermal growth factor receptor (EGFR) signaling with the combination of cetuximab and afatinib.


Patients receive afatinib dimaleate orally (PO) once daily (QD) on days 1-28 and cetuximab intravenously (IV) on day 1 and then every 7 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 4 weeks for up to 24 weeks, then monthly thereafter.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Yale University

Principal Investigator
Aarti Bhatia

  • Primary ID 1608018260
  • Secondary IDs NCI-2017-00236
  • ID NCT02979977