Clinical Trials /

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

NCT02979977

Description:

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.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 1608018260
  • NCT ID: NCT02979977

Conditions

  • Squamous Cell Cancers of the Head and Neck

Interventions

DrugSynonymsArms
cetuximabErbituxAll subjects
afatinibGIOTRIF or GILOTRIFAll subjects

Purpose

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

      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.
    

Trial Arms

NameTypeDescriptionInterventions
All subjectsExperimentalAdvanced 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.
  • cetuximab
  • afatinib

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) ≥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).

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Tumor shrinkage
Time Frame:Disease progression or end of treatment (up to 2 years)
Safety Issue:
Description: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

Measure:Progression-free survival in weeks
Time Frame:1 year follow-up
Safety Issue:
Description:We will use Kaplan-Meier survival analysis to estimate the median PFS in the cohort.
Measure:Overall survival in months
Time Frame:1 year follow-up
Safety Issue:
Description:Measured by a monthly phone calls. We will use Kaplan-Meier survival analysis to estimate the median and OS in the cohort.
Measure:Duration of response in weeks
Time Frame:1 year follow-up
Safety Issue:
Description:
Measure:Toxicity assessed with National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame:Up to 2.5 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Yale University

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