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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 : July 11, 2019
Sponsor:
Collaborators:
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.

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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.
Other Name: GIOTRIF or GILOTRIF




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



Information from the National Library of Medicine

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

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 ClinicalTrials.gov identifier (NCT number): NCT02979977


Contacts
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Contact: Julie Holub, CCRP 203-737-4784 julie.holub@yale.edu

Locations
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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         
Sponsors and Collaborators
Yale University
National Comprehensive Cancer Network
Boehringer Ingelheim
Investigators
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Principal Investigator: Aarti Bhatia, MD, MPH Yale University

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02979977     History of Changes
Other Study ID Numbers: 1608018260
First Posted: December 2, 2016    Key Record Dates
Last Update Posted: July 11, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma
Neoplasms by Site
Cetuximab
Afatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action