A Phase II Trial of PF-00299804 in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of Esophagus
Status:
Completed
Trial end date:
2015-10-01
Target enrollment:
Participant gender:
Summary
Esophageal cancer (EC) is the eighth most common cause of cancer-related death in the
worldwide. Systemic chemotherapy in patients with metastatic EC has limited effectiveness,
resulting in a median survival of 8 months to 10months. The low activity and brief duration
of benefit for chemotherapy to palliate advanced disease make clear need to identify new
active agents.
Epidermal growth factor receptor (EGFR) is often over-expressed, and have been related to
poor prognosis in patients with EC. The association between EGFR-activated signaling pathways
and tumor cell survival are well documented in many studies. Some EGFR tyrosine kinase
inhibitors (TKIs) already showed clinical efficacy against EC. A study with erlotinib showed
objective response rate of 15% (2 of 13 patients), but activity was limited to squamous cell
type.8 In another study, thirty patients with malignant solid tumor were treated with
BIBW2992, irreversible inhibitor of EGFR and HER2, and one of four EC patients achieved
partial response.
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. PF-00299804 reportedly have clinical anti-tumor
activity in patients with non-small cell lung cancer and head and neck squamous cell
carcinoma with manageable toxicity.
The aim of current trial is to evaluate the antitumor efficacy and safety profile of
PF-00299804 and to identify biomarker to predict the tumor response to PF-00299804.