A Phase II Trial of PF-00299804 in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of Esophagus
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
- Overall Response Rate [ Time Frame: 28th day of every chemotherapy cycle ] [ Designated as safety issue: No ]Objective Tumor Response will be performed according to the Response Evaluation in Solid Tumor Criteria (RECIST).
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||March 2015|
|Estimated Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
45 mg p.o. daily and continuously (28-day treatment as one treatment cycle)
Please refer to this study by its ClinicalTrials.gov identifier: NCT01608022
|Contact: Byoung Chul Cho, MD, PhDemail@example.com|
|Korea, Republic of|
|Seoul, Korea, Republic of, 120-752|
|Contact: Joo-Hang Kim, MD PhD 82-2-2222-8131 KJHANG@yuhs.ac|
|Principal Investigator: Byoung Chul Cho, MD, PhD|