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

Study Overview
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Brief Summary
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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.

Detailed Description
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PRIMARY OBJECTIVES: 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. SECONDARY OBJECTIVES: 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.

Official Title
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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

Conditions
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Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: afatinib
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (afatinib)<br>Patients receive afatinib PO QD on days 1-28. | Drug: afatinib<br>* Given PO<br>* Other names: BIBW 2992;|
| Placebo Comparator: Arm B (placebo)<br>Patients receive placebo PO QD on days 1-28. | Other: placebo<br>* Given PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free Survival (DFS) | DFS is defined as the time from randomization to the earlier of disease recurrence, second primary cancer, or death without recurrence. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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afatinib, head and neck squamous cell carcinoma