Ignite Creation Date:
2024-05-05 @ 5:34 PM
Last Modification Date:
2024-10-26 @ 9:33 AM
Study NCT ID:
NCT00486668
Status:
UNKNOWN
Last Update Posted:
2016-06-06
First Post:
2007-06-13
Brief Title:
A Study of AC Followed by a Combination of Paclitaxel Plus Trastuzumab or Lapatinib or Both Given Before Surgery to Patients With Operable HER2 Positive Invasive Breast Cancer
Sponsor:
NSABP Foundation Inc
Organization:
NSABP Foundation Inc
Study Overview
Official Title:
A Randomized Phase III Trial of Neoadjuvant Therapy for Patients With Palpable and Operable HER2-Positive Breast Cancer Comparing the Combination of Trastuzumab Plus Lapatinib to Trastuzumab and to Lapatinib Administered With Weekly Paclitaxel Following AC Accompanied by Correlative Science Studies to Identify Predictors of Pathologic Complete Response
Status:
UNKNOWN
Status Verified Date:
2016-06
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The primary purpose of this study is to determine whether breast cancer tumors respond as measured by pathologic complete response the absence of microscopic evidence of invasive tumor cells in the breast to combined chemotherapy of ACdoxorubicin and cyclophosphamide followed by paclitaxel plus trastuzumab or lapatinib or both given before surgery to patients with HER2-positive breast cancer Trastuzumab will also be given to all patients after surgery The study will also evaluate the toxic effects of the chemotherapy combination including effects on the heart and will determine survival and progression-free survival 5 years after treatment Also the study will look at whether there are gene expression profiles in the tumor tissue that can predict pathologic complete response
Detailed Description:
Women with breast cancers that overexpress HER2 are at greater risk for disease progression and death than women whose tumors do not overexpress HER2 Trastuzumab a recombinant humanized monoclonal antibody against the extracellular domain of the HER2 protein blocks downstream signaling of HER2 and substantially improves the efficacy of chemotherapy in women with metastatic and early-stage HER2-positive breast cancers Because resistance to trastuzumab eventually results in progressive disease in the metastatic setting and contributes to recurrence following adjuvant trastuzumab-based therapy it is important to develop agents other than trastuzumab that target HER2 signaling through different mechanisms of action Lapatinib is an oral small molecule dual tyrosine kinase inhibitor of HER2 and EGFR Lapatinib has shown a lack of cross-resistance with trastuzumab in preclinical studies and activity in women with HER2-positive metastatic breast cancer that has progressed during trastuzumab treatment Trastuzumab blocks the downstream signaling of HER2 by binding to the extracellular domain of the receptor Lapatinib binds to the intracellular domains of HER2 and EGFR and prevents activation of downstream signaling pathways Because of this different mechanism of action lapatinib may be effective in trastuzumab-resistant disease The study will also provide important safety information on trastuzumab and lapatinib combinations immediately following anthracycline exposure and also provide an initial direct comparison of cardiac effects of trastuzumab and lapatinib when incorporated into a standard sequential AC followed by weekly paclitaxel neoadjuvant regimen
Availability of a second agent that can interrupt HER2-signaling pathways through completely different mechanisms than those of trastuzumab offers the potential for further improvement in the management of patients with HER2-overexpressing breast cancer in both the adjuvant and metastatic setting Co-administration of both trastuzumab and lapatinib with chemotherapy may be important in improving outcomes in subsets of HER2-positive breast cancers However use of two inhibitors of the HER2 pathway will increase costs and may increase toxicity so it will be important to identify the subsets of patients who would benefit from the dual therapy Inhibition of HER2 with a single agent clearly is sufficient for many patients as evidenced by the results of the trastuzumab trials Therefore co-administration to unselected populations of women with HER2-positive breast cancers would not represent an optimal approach Given the activity of lapatinib it is likely that it will also be sufficiently active in inhibiting HER2-pathway activation in some patients to allow for its use as the sole inhibitor of the HER2 pathway Different populations may also derive greater benefit from one of the HER2-blocking agents relative to the other Identification of potential predictive factors for pathologic complete response to the combination or to either agent administered alone in neoadjuvant trials would provide important information for adjuvant trials designed to definitively address these important issues
This study will compare 3 combined chemotherapy regimens AC followed by paclitaxel plus trastuzumab and lapatinib AC followed by paclitaxel plus lapatinib and AC followed by paclitaxel plus trastuzumab given before surgery to patients with HER2-positive breast cancer
Availability of a second agent that can interrupt HER2-signaling pathways through completely different mechanisms than those of trastuzumab offers the potential for further improvement in the management of patients with HER2-overexpressing breast cancer in both the adjuvant and metastatic setting Co-administration of both trastuzumab and lapatinib with chemotherapy may be important in improving outcomes in subsets of HER2-positive breast cancers However use of two inhibitors of the HER2 pathway will increase costs and may increase toxicity so it will be important to identify the subsets of patients who would benefit from the dual therapy Inhibition of HER2 with a single agent clearly is sufficient for many patients as evidenced by the results of the trastuzumab trials Therefore co-administration to unselected populations of women with HER2-positive breast cancers would not represent an optimal approach Given the activity of lapatinib it is likely that it will also be sufficiently active in inhibiting HER2-pathway activation in some patients to allow for its use as the sole inhibitor of the HER2 pathway Different populations may also derive greater benefit from one of the HER2-blocking agents relative to the other Identification of potential predictive factors for pathologic complete response to the combination or to either agent administered alone in neoadjuvant trials would provide important information for adjuvant trials designed to definitively address these important issues
This study will compare 3 combined chemotherapy regimens AC followed by paclitaxel plus trastuzumab and lapatinib AC followed by paclitaxel plus lapatinib and AC followed by paclitaxel plus trastuzumab given before surgery to patients with HER2-positive breast cancer
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None