NCT01152853

PF-00299804 Monotherapy in Patients With HER-2 Positive Advance Gastric Cancer

A Phase II Open Label Trial of PF-00299804 Monotherapy in Patients With HER-2 Positive Advance Gastric Cancer After Failure of At Least One Prior Chemotherapy Regimen

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Seoul National University Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

In case of gastric cancer, the incidence of HER-2 positivity (2+, 3+ on IHC and/or FISH (+)) is reported as similar as that of breast cancer, that is 22% of all cases. A recent ToGA Trial, phase III trial comparing trastuzumab combined with chemotherapy (fluoropyrimidine+cisplatin) versus chemotherapy alone in chemotherapy-naïve HER-2 (+) gastric cancer shows the significant benefit of using trastuzumab in terms of overall survival and progression-free survival. It provides the clinical evidence of HER-2 as a reasonable and potential therapeutic target in gastric cancer. Nowadays, lapatinib, HER-1 and HER-2 dual inhibitor, is also testing under the clinical trial in gastric cancer. In preclinical study, PF-00299804 is highly active in HER-2 amplified gastric cancer cell lines.(SNU preclinical data) So, we plan this phase II trial of PF-00299804 monotherapy in patients with HER-2 positive advance gastric cancer after failure of at least one chemotherapy regimen.

Detailed description

The role of HER-2 during carcinogenesis and its prognostic role in breast cancer has been already well established. Furthermore the value of HER-2 as a reasonable therapeutic target in breast cancer has translated into the good clinical therapeutic result using HER-2 targeting agent, such as trastuzumab and lapatinib. In case of gastric cancer, the incidence of HER-2 positivity (2+, 3+ on IHC and/or FISH (+)) is reported as similar as that of breast cancer, that is 22% of all cases. A recent ToGA Trial, phase III trial comparing trastuzumab combined with chemotherapy (fluoropyrimidine+cisplatin) versus chemotherapy alone in chemotherapy-naïve HER-2 (+) gastric cancer shows the significant benefit of using trastuzumab in terms of overall survival and progression-free survival. It provides the clinical evidence of HER-2 as a reasonable and potential therapeutic target in gastric cancer. Nowadays, lapatinib, HER-1 and HER-2 dual inhibitor, is also testing under the clinical trial in gastric cancer. PF-00299804 is an orally available, potent, and highly selective irreversible small molecule inhibitor of the Human Epidermal Growth Factor Receptor (HER) family of tyrosine kinases:HER-1 (EGFR), HER-2 and HER-4 (HER-3 does not possess kinase activity). PF-00299804 inhibits the tyrosine kinase activity of the HER family through binding at the ATP binding site, which results in covalent modification of a cystine in the ATP binding pocket. The unique irreversible and highly selective properties of PF-00299804 for the HER kinase family results in sustained suppression of receptor tyrosine kinase activity. The long-lasting inhibition of receptor phosphorylation reduces concern over potentially short plasma half-lives. Furthermore, the low nanomolar potency and irreversible binding of the intended targets reduce the need for high peak plasma levels, which in turn could minimize target-nonspecific toxicities. In preclinical study, PF-00299804 is highly active in HER-2 amplified gastric cancer cell lines.(SNU preclinical data) Overall, the standard of care for advanced gastric cancer has been of modest benefit with plateau in response rates using various combination chemotherapies. Therefore, development of treatment options for these advanced gastric cancer patients, especially HER-2 (+) gastric cancer patients, remains a target of active research. So, the investigators plan this phase II trial of PF-00299804 monotherapy in patients with HER-2 positive advance gastric cancer after failure of at least one chemotherapy regimen.

Conditions

• Advanced Gastric Cancer
• HER2

Interventions

Type	Name	Description
DRUG	PF00299804	PF-00299804 will be given orally once daily at 45 mg daily. Patients will take study drug continuously, with cycles of 28 days.

Timeline

• Start date: 2010-07-01
• Primary completion: 2011-07-01
• Completion: 2012-09-01
• First posted: 2010-06-29
• Last updated: 2015-11-20

Locations

1 site across 1 country: South Korea