Lapatinib and Radiation for Stage III-IV Head and Neck Cancer Patients Who Cannot Tolerate Concurrent Chemotherapy
Condition: Head and Neck Cancer; Carcinoma, Squamous Cell; Head and Neck Cancers
MeSH terms: Head and Neck Neoplasms; Carcinoma, Squamous Cell
Intervention: Lapatinib; Radiotherapy (radiation); G.E. Healthcare 1.5T MR, systems revision 12.0 M5; DCE-MRI
Intervention description: 1500 mg po daily orally; Standard of Care; Standard of Care, used to deliver IMRT; A subset of patients received imaging before and after Lapatinib loading, prior to starting radiotherapy.
Intervention MeSH terms: Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      We propose to combine lapatinib with RT alone in patients with locally advanced head and neck
      cancer who cannot tolerate chemotherapy. The main objective of the study is to determine the
      efficacy of combining concurrent radiation and lapatinib in terms of time-to-progression
      (TTP) in this group of patients. In addition, we will determine the 2-year locoregional
      control rate (LRC), progression-free survival (PFS) and overall survival (OS) in these
      patients. We will also evaluate the profile and frequency of late toxicity, specifically
      mucosal and dermatologic toxicity, of the combination of lapatinib and RT in patients with
      locally advanced head and neck squamous cell carcinoma (HNSCC).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Newly diagnosed stage III-IV HNSCC, pathologically confirmed (HNSCC from unknown
             primary sites are allowed)

          -  No evidence of distant metastasis

          -  No prior radiation therapy to the head and neck sites.

          -  Able to sign a study-specific informed consent form.

          -  Women of childbearing potential and men with partners capable of producing offspring
             must be willing to practice acceptable methods of birth control to prevent pregnancy.

          -  Left ventricular ejection fraction (LVEF) within the institutional normal range as
             measured by ECHO (If ECHO cannot be performed or if the Investigator feels that it is
             not conclusive to evaluate LVEF, then a MUGA scan should be performed).

          -  Having one of the following parameters that would preclude the use of concurrent CRT:

               -  ECOG PS > 2.

               -  Creatinine > 1.3 or calculate or measure creatinine clearance < 60 ml/min.

               -  AST or ALT > 1.5 times normal limit but < 3 times normal limit

               -  Total bilirubin > 1.5 mg/dL but < 3mg/dL

               -  History of hearing loss that would preclude cisplatin chemotherapy. These would
                  include the existing need of a hearing aid or a >= 25 decibel shift over 2
                  contiguous frequencies on a pretreatment hearing test.

               -  Pre-existing peripheral neuropathy that would preclude cisplatin chemotherapy

               -  Refuse or cannot tolerate chemotherapy

          -  Age 18 years or older

        Exclusion Criteria:

          -  Known hypersensitivity to lapatinib or any of the excipients of this product
             (quinazolines).

          -  Uncontrolled angina, arrhythmia or congestive heart failure at the time of HNSCC
             diagnosis and treatment.

          -  History of myocardial infarction < 6 months from study entry.

          -  Treatment with a non-approved or investigational drug within 30 days before Day 1 of
             study treatment.

          -  Prior treatment with EGFR or Her2/Neu directed therapies.

          -  HIV-positive patients receiving combination anti-retroviral therapy are excluded from
             the study because of possible pharmacokinetic interactions with Lapatinib.

          -  Absolute neutrophil count < 1500/uL