INST 0514C- Biologic Correlative Study: Trial of GW572016 in HER2 Overexpressing Breast Cancer Patients
Neoadjuvant chemotherapy has become the standard of care for breast cancer patients with large tumors in order to render them operable for mastectomy or, in some cases, for lumpectomy and radiation therapy. Building on this theme, several large hormonal therapies are extensively investigated in the neoadjuvant setting, together with biologic correlates for response and resistance. As a further extension, neoadjuvant therapies with biologic agents are now too, being investigated for biologic evidence of efficacy before large-scale clinical trials of thousands of patients are embarked on. The neoadjuvant setting is especially attractive for these studies for several reasons including early assessment of response to therapy, biopsiable access to the primary tumor, and considerable reduced sample sizes compared to those required in the adjuvant setting. In addition, clinical response to neoadjuvant chemotherapy is a validated surrogate marker for improved survival. It may be used to test the overall efficacy of neoadjuvant treatment regimens and mirrors the effect of therapy on micrometastases setting. In a recent study, good clinical response to neoadjuvant chemotherapy was the only independent variable, by multivariate analysis, associated with decreased risk of death.
GW572016 is a new and promising dual tyrosine kinase inhibitor against HER1/2. Hundreds of patients were treated in phase I and II studies world-wide and results indicate that this reversible, oral small molecule is generally well-tolerated. Studies of neoadjuvant Trastuzumab indicate that HER2 interference leads to significant tumor regression even after 3 weeks of monotherapy. We aim to extend these findings with a novel agent, GW572016 that may be more effective, especially from its in vitro data, and to discover the true response rate to inhibiting HER1/2 signal transduction in breast cancer patients.
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||INST 0514C- A Neoadjuvant Phase II Trial of GW572016 in HER2 Overexpressing Breast Cancer Patients: Biologic Correlative Study|
- The primary end point of this study is clinical efficacy of GW572016 in treatment naïve patients with locally advanced breast cancer. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
- The secondary end points would be the biologic correlative of relevant biomarkers. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||July 2005|
|Study Completion Date:||October 2009|
|Primary Completion Date:||October 2009 (Final data collection date for primary outcome measure)|
|United States, New Mexico|
|Albuquerque, New Mexico, United States, 87106|
|Principal Investigator:||Melanie Royce, MD||University of New Mexico Cancer Center|