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
Condition: Head and Neck Squamous Cell Carcinoma
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Recurrence
Intervention: afatinib; placebo
Intervention description: Given PO; Given PO
Intervention MeSH terms: Afatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: afatinib; head and neck squamous cell carcinoma

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.
    

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