PF-00299804 in Patients With Head and Neck Squamous Cell Carcinoma

• Best objective response [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]
  Tumor assessment by RECIST criteria version 1.1 will be followed every 8 weeks treatment until disease progression
• Progression-free survival [ Time Frame: every 8 weeks ] [ Designated as safety issue: No ]
  from C1D1 until confirmed disease progression or death
• Overall survival [ Time Frame: every 12 weeks ] [ Designated as safety issue: No ]
  from C1D1 to death
• Toxicity profile [ Time Frame: every 4 weeks ] [ Designated as safety issue: No ]
  from C1D1 to 1 months after the last dose adminitration

• Best objective response [ Time Frame: OCT 2012 [anticipated] ] [ Designated as safety issue: No ]
  Tumor assessment by RECIST criteria version 1.1 will be followed at the end of first 28-day treatment, then every 48-day treatment until disease progression
• Progression-free survival [ Time Frame: APR 2013 [anticipated] ] [ Designated as safety issue: No ]
• Overall survival [ Time Frame: APR 2013 [anticipated] ] [ Designated as safety issue: No ]
• Toxicity profile [ Time Frame: OCT 2012 [anticipated] ] [ Designated as safety issue: No ]
  Check every cycle day 1 and every unscheduled visit
• Predictive biomarker analysis [ Time Frame: APR 2013 [anticipated] ] [ Designated as safety issue: No ]
  EGFR pathway analysis
• Duration of response [ Time Frame: OCT 2012 [anticipated] ] [ Designated as safety issue: No ]

Epidermal growth factor receptor (EGFR) is often over-expressed, and have been related to poor prognosis in patients with HNSCC. EGFR targeting strategies showed clinical anti-tumor efficacy in patients with HNSCC. PF-00299804 is a second-generation quinazoline-based irreversible pan-HER inhibitor. In preclinical studies, PF-00299804 has much lower IC50 values than gefitinib in cell lines engineered to express EGFRvIII mutations (1.2 nM versus 2,700 nM) and produces tumor growth inhibition in gefitinib-resistant xenografts. A phase II trial of PF-00299804 in patients with recurrent or metastatic HNSCC is currently ongoing and preliminary report in ASCO 2010 showed its anti-tumor activity against HNSCC. The investigators suggest a phase II trial of pan-HER inhibitor PF-00299804 in patients with recurrent or metastatic HNSCC previously treated with platinum-based chemotherapy.

• Head Neck Cancer Squamous Cell Metastatic
• Head Neck Cancer Squamous Cell Recurrent

Inclusion Criteria:

• Histologically confirmed squamous cell carcinoma of head and neck
• Age ≥ 18
• ECOG PS 0-2
• Documented progressive disease after platinum-based systemic chemotherapy (either cisplatin or carboplatin) with or without cetuximab
• At least one bidimensionally measurable disease
• Adequate organ function for treatment
• Availability of tumor tissue for molecular analysis (archival or rebiopsy tissue)

Exclusion Criteria:

• Nasopharyngeal carcinoma
• Eligibility for local therapy (surgery or radiotherapy)
• Previous treatment with small molecule EGFR tyrosine kinase inhibitors
• More than one systemic chemotherapy
• Any major operation or irradiation within 4 weeks of baseline disease assessment
• Any clinically significant gastrointestinal abnormalities which may impair intake or absorption of the study drug
• CNS metastasis with continuous corticosteroid use within 4 weeks of baseline disease assessment
• Patients with known interstitial lung disease
• Patients with uncontrolled or significant cardiovascular disease (AMI within 12 months, Unstable angina within 6 months, NYHA Class III, IV Congestive heart failure or left ventricular ejection fraction below local institutional lower limit of normal or below 45%, Congenital long QT syndrome, Any significant ventricular arrhythmia, Any uncontrolled second or third degree heart block, Uncontrolled hypertension)
• Concomitant malignancy (except adequately treated basal cell cancer of skin or cervical cancer in situ)
• Pregnant or breast-feeding women
• Other severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial.