Ignite Creation Date:
2024-05-05 @ 12:08 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00256243
Status:
COMPLETED
Last Update Posted:
2018-03-02
First Post:
2005-11-17
Brief Title:
Neoadjuvant Biweekly Treatment Followed by Weekly Treatment of Breast Cancer
Sponsor:
Rita Sanghvi Mehta
Organization:
University of California Irvine
Study Overview
Official Title:
A Pilot Study of Neoadjuvant Biweekly Doxorubicin and Cyclophosphamide AC With GMCSF Followed by Weekly CarboplatinPaclitaxel With Plus or Minus Trastuzumab TC H in the Treatment of Breast Cancer
Status:
COMPLETED
Status Verified Date:
2018-02
Last Known Status:
None
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:
We proposed to use 4 cycles of AC q 2 weeks as used in the dose dense adjuvant study with GM-CSF support on days 3-9 of the cycle After the completion of AC we plan to administer paclitaxel and carboplatin weekly for a total of 12 doses with one week rest after every 3 weeks of treatment over 12 weeks Patients who are her-2 over-expressors by FISH fluorescence in situ hybridization will also receive Trastuzumab with weekly carboplatin and paclitaxel as the combination TCH has been found to be synergistic in advanced breast cancer with improved clinical outcome
Detailed Description:
Neoadjuvant chemotherapy also termed primary induction or preoperative chemotherapy is defined as chemotherapy administered before locoregional treatment It was first used in locally advanced breast cancer 30 years ago Classically these tumors were treated with radical surgery andor radiotherapy However despite this aggressive local therapy most patients relapsed with distant metastases and eventually died 12 The aim of neoadjuvant therapy is to reduce the tumor volume in patients before surgical resection thus increasing the likelihood of breast conservation More recently neoadjuvant therapy has been studied as a way of testing the relevance of biological markers in predicting disease outcome
At least six randomized trials have compared survival in patients managed with either the neoadjuvant or adjuvant approaches3456789 Two of the smaller trials suggested a survival advantage for patients treated with neoadjuvant chemotherapy 56 Other studies including the largest trial 1523 patients run by the NSABP found no differences in disease-free and overall survival 469
Induction of a pCR should be one of the primary goals of neoadjuvant therapy because patients with no evidence of tumor cells in breast and lymph nodes after treatment may have a longer disease-free and overall survival 10
Biweekly and weekly regimens may enhance dose intensity by minimizing re-growth of cells between cycles of treatment In fact dose dense regimens have even shown a survival benefit in an adjuvant setting in lymph node positive breast cancer made possible with use of G-CSF 11 There is as yet no standard best neoadjuvant treatment Generally patients receive AC NSABP 14 on 3-weekly regimens in neoadjuvant setting In addition incorporation of taxanes on a 3 weekly schedule has resulted in statistically higher pathological CR 1213 More recently weekly paclitaxel regimens have reported increased pathological responses compared to 3 weekly taxane regimens Carboplatin has also emerged as an effective agent in the treatment of metastatic breast cancer 14 Moreover the combination of carboplatin and paclitaxel has been found to be synergistic both in three-weekly regimens and weekly regimens In fact combination of carboplatin paclitaxel and trastuzumab has demonstrated a survival advantage over paclitaxel and trastuzumab alone The Phase III study the preliminary results of which were presented at the San Antonio Breast Cancer Symposium show that the addition of carboplatin to trastuzumab and paclitaxel resulted in a six-month improvement in the time it took for the disease to progress compared to the standard trastuzumab and paclitaxel regimen The study found median survival in the trastuzumab and paclitaxel arm was 335 months while the group receiving the tripartite therapy had yet to reach that point after 36 months of follow-up Furthermore the weekly regimens of these drugs have been found to have significantly improved tolerability over three weekly regimens 15 Therefore we propose to use 4 cycles of AC q 2 weeks as used in the dose dense adjuvant study with GM-CSF support on days 5-14 of the cycle After the completion of AC we plan to administer taxol and carboplatin weekly for a total of 9 doses with one week rest after every 3 weeks of treatment over 12 weeks
Patients who are her-2 overexpressors by FISH will also receive Trastuzumab with weekly carboplatin and paclitaxel as the combination has been found to be synergistic in advanced breast cancer with improved clinical outcome
In a separate trial GMCSF was used in breast cancer patients treated with adriamycin based chemotherapy as the preferred growth factor in a neoadjuvant setting 16 The initial results are suggestive of improved survival of breast cancer patients given 6 versus 5 versus 4 cycles of chemotherapy with GMCSF support Higher dendritic cell DC trafficking showed a trend toward improved survival Moreover intrapatient comparison before and after treatment showed that the percentage of S100 DC significantly increased over the course of GM-CSF treatment The results form the basis of current hypothesis that the primary tumor may be an in vivo antigenic stimulus for dendritic cell trafficking and that the combination of prolonged neoadjuvant chemotherapy with GM-CSF induced immune enhancement may contribute to better tumor control and better survival
At least six randomized trials have compared survival in patients managed with either the neoadjuvant or adjuvant approaches3456789 Two of the smaller trials suggested a survival advantage for patients treated with neoadjuvant chemotherapy 56 Other studies including the largest trial 1523 patients run by the NSABP found no differences in disease-free and overall survival 469
Induction of a pCR should be one of the primary goals of neoadjuvant therapy because patients with no evidence of tumor cells in breast and lymph nodes after treatment may have a longer disease-free and overall survival 10
Biweekly and weekly regimens may enhance dose intensity by minimizing re-growth of cells between cycles of treatment In fact dose dense regimens have even shown a survival benefit in an adjuvant setting in lymph node positive breast cancer made possible with use of G-CSF 11 There is as yet no standard best neoadjuvant treatment Generally patients receive AC NSABP 14 on 3-weekly regimens in neoadjuvant setting In addition incorporation of taxanes on a 3 weekly schedule has resulted in statistically higher pathological CR 1213 More recently weekly paclitaxel regimens have reported increased pathological responses compared to 3 weekly taxane regimens Carboplatin has also emerged as an effective agent in the treatment of metastatic breast cancer 14 Moreover the combination of carboplatin and paclitaxel has been found to be synergistic both in three-weekly regimens and weekly regimens In fact combination of carboplatin paclitaxel and trastuzumab has demonstrated a survival advantage over paclitaxel and trastuzumab alone The Phase III study the preliminary results of which were presented at the San Antonio Breast Cancer Symposium show that the addition of carboplatin to trastuzumab and paclitaxel resulted in a six-month improvement in the time it took for the disease to progress compared to the standard trastuzumab and paclitaxel regimen The study found median survival in the trastuzumab and paclitaxel arm was 335 months while the group receiving the tripartite therapy had yet to reach that point after 36 months of follow-up Furthermore the weekly regimens of these drugs have been found to have significantly improved tolerability over three weekly regimens 15 Therefore we propose to use 4 cycles of AC q 2 weeks as used in the dose dense adjuvant study with GM-CSF support on days 5-14 of the cycle After the completion of AC we plan to administer taxol and carboplatin weekly for a total of 9 doses with one week rest after every 3 weeks of treatment over 12 weeks
Patients who are her-2 overexpressors by FISH will also receive Trastuzumab with weekly carboplatin and paclitaxel as the combination has been found to be synergistic in advanced breast cancer with improved clinical outcome
In a separate trial GMCSF was used in breast cancer patients treated with adriamycin based chemotherapy as the preferred growth factor in a neoadjuvant setting 16 The initial results are suggestive of improved survival of breast cancer patients given 6 versus 5 versus 4 cycles of chemotherapy with GMCSF support Higher dendritic cell DC trafficking showed a trend toward improved survival Moreover intrapatient comparison before and after treatment showed that the percentage of S100 DC significantly increased over the course of GM-CSF treatment The results form the basis of current hypothesis that the primary tumor may be an in vivo antigenic stimulus for dendritic cell trafficking and that the combination of prolonged neoadjuvant chemotherapy with GM-CSF induced immune enhancement may contribute to better tumor control and better survival
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2004-3517 | OTHER | University of California Irvine | None |