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Afatinib After Chemoradiation and Surgery in Treating Patients With Stage III-IV Squamous Cell Carcinoma of the Head and Neck at High-Risk of Recurrence

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ClinicalTrials.gov Identifier: NCT01824823
Recruitment Status : Terminated (Slow accrual)
First Posted : April 5, 2013
Results First Posted : April 4, 2016
Last Update Posted : January 27, 2021
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )

Brief Summary:
This randomized phase II trial studies how well giving afatinib after chemoradiation and surgery works in treating patients with stage III-IV squamous cell carcinoma of the head and neck at high-risk of recurrence. Afatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Drug: afatinib Other: placebo Phase 2

Detailed Description:


I. Examine disease-free survival (DFS) given afatinib/placebo adjuvant therapy in patients with viable tumors in lymph nodes after neck dissection for suspected residual disease after concurrent chemoradiation.


I. Evaluate the recurrence rate, recurrence patterns, development of second primary malignancies, overall survival (OS) and toxicity of afatinib/placebo.

II. Evaluate on-target inhibition by afatinib, and determine circulating deoxyribonucleic acid (DNA) as a biomarker of afatinib resistance.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive afatinib orally (PO) once daily (QD) on days 1-28.

ARM B: Patients receive placebo PO QD on days 1-28.

In both Arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 1 year and then every 12 months for 2 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Placebo Controlled Phase II Trial of Afatinib (BIBW2992) as Adjuvant Therapy Following Chemoradiation in Patients With Head and Neck Squamous Cell Carcinoma at High Risk of Recurrence
Actual Study Start Date : July 11, 2013
Actual Primary Completion Date : December 13, 2015
Actual Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Arm A (afatinib)
Patients receive afatinib PO QD on days 1-28.
Drug: afatinib
Given PO
Other Name: BIBW 2992

Placebo Comparator: Arm B (placebo)
Patients receive placebo PO QD on days 1-28.
Other: placebo
Given PO

Primary Outcome Measures :
  1. Disease-free Survival (DFS) [ Time Frame: Assessed every 3 months for patients < 2 years from registration and every 6 months if patient is 2-3 years from registration and every 12 months if patient is 4-5 years from registration ]
    DFS is defined as the time from randomization to the earlier of disease recurrence, second primary cancer, or death without recurrence.

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

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Patients must have pathological evidence of persistent primary and/or lymph node disease with viable tumor cells following primary concurrent chemoradiotherapy of locoregionally advanced (stage III/IV) HNSCC of the oral cavity, oropharynx, larynx, hypopharynx or p16-positive unknown primary of the head and neck region; persistent primary and/or lymph node disease with viable tumor cells will be determined by the histological determination of tumor viability defined as tumor cells with intact cellular compartments (i.e. cytoplasm and nucleus) that do not exhibit karyolysis, pyknosis, or karyorrhexis on haematoxylin and eosin (H&E) staining
  • Patients must have undergone a neck dissection following completion of chemoradiotherapy and must have involved at the minimum a compartment dissection of nodal levels with residual abnormalities on post-treatment imaging studies and/or received a complete resection of the residual primary lesion with negative margins
  • Patients must have achieved a complete response at the primary disease site after chemoradiotherapy or complete resection of the residual primary site disease with negative margins
  • All persistent lymph node disease must have received at least 66 Gy of radiotherapy and must have been completely surgically resected prior to registration, and surgical incisions should be adequately healed
  • Patients with extracapsular lymph node extension, perineural or lymphovascular invasion will be eligible
  • Patients must be at least 6 weeks (42 days) and no more than 36 weeks (252 days) from completion of chemoradiation at the time of registration
  • Patients will be eligible regardless of ability to swallow; patients with dysphagia may have afatinib/placebo administered via gastrostomy tube
  • Absolute neutrophil count >= 1,000/mm^3
  • Platelets >= 100,000/mm^3
  • Total bilirubin =< 1.5 x the upper limit of normal (ULN)
  • Aspartate amino transferase (AST) =< 3 x the ULN
  • Alanine amino transferase (ALT) =< 3 x the ULN
  • Calculated creatinine clearance must be >= 50 ml/min using the Cockcroft-Gault formula
  • Prior cetuximab or any epidermal growth factor receptor (EGFR) inhibitors will not be permitted including cetuximab administered with a chemoradiotherapy or radiotherapy regimen
  • As all patients in this study will have received prior full dose, curative-intent external-beam radiotherapy to the involved neck, no additional external-beam radiotherapy will be permitted prior to or during study participation
  • Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception
  • Patients must have electrocardiogram (ECG) within 8 weeks prior to randomization to the study
  • Patients must be assessed for cardiac function by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) within 8 weeks prior to randomization

Exclusion Criteria:

  • Patients with known distant metastatic disease or with any gross residual disease following salvage primary tumor resection or neck dissection
  • Known hypersensitivity to afatinib or any of the excipients of this product
  • Prior adjuvant chemotherapy (aside from the initial induction chemotherapy followed by chemoradiotherapy or chemoradiotherapy regimen)
  • History of acute myocardial infarction within 3 months prior to registration, and any history of uncontrolled angina, uncontrolled arrhythmia, or uncontrolled heart failure
  • Pregnant or breast-feeding women
  • Active infections, other cancers, or history of other cancers
  • Participation in any other clinical trials or taking any other experimental medications
  • Left ventricular dysfunction
  • Evidence of interstitial lung disease

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): NCT01824823

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Sponsors and Collaborators
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
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Principal Investigator: Christine Chung Eastern Cooperative Oncology Group
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Responsible Party: ECOG-ACRIN Cancer Research Group
ClinicalTrials.gov Identifier: NCT01824823    
Other Study ID Numbers: E1311
NCI-2013-00357 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
U10CA021115 ( U.S. NIH Grant/Contract )
First Posted: April 5, 2013    Key Record Dates
Results First Posted: April 4, 2016
Last Update Posted: January 27, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
Keywords provided by Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group ):
head and neck squamous cell carcinoma
Additional relevant MeSH terms:
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Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Disease Attributes
Pathologic Processes
Head and Neck Neoplasms
Neoplasms by Site
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action