Intervention: Afatinib
Trial phase: Phase 2
ATC code: L01EB03 | L01XE13
SMILES: CN(C)C/C=C/C(=O)Nc1cc2c(Nc3ccc(F)c(Cl)c3)ncnc2cc1O[C@H]1CCOC1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 2
Group description: Patients receive afatinib PO QD on days 1-28.
Eligibility criteria:
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