Ignite Creation Date:
2024-05-05 @ 12:00 PM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00206453
Status:
TERMINATED
Last Update Posted:
2013-02-05
First Post:
2005-09-14
Brief Title:
Extension Neoadjuvant Taxotere Study of the Effects of Taxotere in Patients With Breast Cancer
Sponsor:
Baylor Breast Care Center
Organization:
Baylor Breast Care Center
Study Overview
Official Title:
An Extension Phase II Study of the Clinical and Biologic Effects of Docetaxel Taxotere in Patients With Locally Advanced Breast Cancer
Status:
TERMINATED
Status Verified Date:
2013-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
accrual too difficult to meet
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
We the investigators at Baylor Breast Care Cancer are doing this study to learn how well Taxotere makes tumors become smaller We are also doing this study to find out how well Taxotere treats the type of breast cancer that some patients have We are asking patients to take part in this study because they have locally advanced breast cancer Women with this breast cancer will usually receive chemotherapy medicines to reduce or shrink the cancer before surgery to take out the cancer If patients choose to take part in this study they will receive Taxotere and the combination of cyclophosphamide and doxorubicin These medicines are part of the standard good medical care for this type of breast cancer They are approved for the treatment of this problem To help us learn how the patients cancer responds to these medicines we will take a small tissue sample biopsy of the patients breast cancer before beginning treatment one day after the first dose of treatment once each week for the first three weeks of treatment and when surgery is done as part of treatment for their cancer These samples will be collected also to look at the biology of the patients cancer We will also use a new method called cDNA array technology which lets us look at thousands of genes coding information inside the cancer cell at once By looking at different genes in the breast cancer we may learn important information about which cancers will respond to a chemotherapy medicine We hope to learn if there are different gene patterns in patients whose tumors shrink or do not shrink with this chemotherapy medicine This information may help us in the future to choose the right medicines for women with breast cancer so that they have the highest chance of their cancer shrinking with chemotherapy medicine We cannot and do not know if patients will benefit if they take part in this study
Detailed Description:
New treatment strategies are needed to improve the clinical outcome in breast cancer patients at high risk of tumor recurrence Even with the best present combination chemotherapy radiotherapy and surgery the five-year rate of disease recurrence and death is at least 60 in patients with locally advanced breast cancer Recent advances that may improve clinical outcome include the use of taxanes paclitaxel and docetaxel a new class of cytotoxic agents with reported higher response rates than standard anthracycline-based chemotherapy Understanding the in vivo mechanism of action of chemotherapeutic agents would also allow for rational combination of agents For example if apoptosis is the main mechanism of therapeutic action then future developments in restoring function of p53 by gene therapy or treatment with apoptosis regulating molecules may prove to be important future advances in the treatment of cancer If specific therapeutic targets and pathways are identified new molecules with selective action against these targets may be developed which may have potential for decreased toxicity with increased efficacy
To this end we undertook a Phase II clinical trial of neoadjuvant docetaxel Taxotere in patients with locally advanced breast cancer H-8448 with the primary goal of defining the clinical efficacy and the biologic effects of docetaxel The secondary aim of the study was to identify distinctive gene expression patterns predictive of response to docetaxel chemotherapy For this we proposed to use microarray expression technology Affymetrix U95A and allied validation technologies eg IHC western blot quantitative RT-PCR to identify and validate patterns of gene expression associated with chemotherapy sensitivity or resistance
The purpose of this Phase II extension study is to determine the biologic effects of docetaxel Taxotere to identify gene expression profiles predictive of response and to further describe the efficacy of Taxotere in women with locally advanced breast cancer In addition to surgical operability and clinical response the endpoints will include the comparison of histologic and molecular markers from sequential core biopsies of primary breast cancers of patients receiving Taxotere Expression arrays will be used to identify and validate patterns of gene expression associated with Taxotere sensitivity or resistance
Clinical study A diagnostic core biopsy will be performed prestudy and tissue obtained from this will be available for analysis Other required baseline investigations including CBC kidney function tests liver function tests EKG and pregnancy tests are part of the standard of care Docetaxel Taxotere 100 mgm2 is to be administered on day 1 A core biopsy is to be performed one day after chemotherapy day 2 and on days 8 15 and 22 On day 22 after repeat core biopsy a second cycle of docetaxel Taxotere chemotherapy 100 mgm2 will be given Docetaxel Taxotere will be given three-weekly for a total of four cycles Primary surgery will then be conducted if operable following completion of neoadjuvant treatment Adjuvant AC doxorubicin 60 mgm2 and cyclophosphamide 600 mgm2 every three weeks for four cycles will then be administered Adjuvant radiotherapy will be considered following completion of AC chemotherapy Patients whose tumors were ER andor PgR positive would be commenced on tamoxifen for five years after completion of AC chemotherapy
Core biopsies Core biopsies for biologic marker evaluation will be performed prestudy excess from diagnostic biopsy and on days 2 8 15 and 22 following entry into study Tissue for analysis will also be obtained at surgery Prestudy biopsy and specimen at surgery will be part of standard of care while four additional biopsies will be performed solely for research purposes only Thus a total of six biopsies will be obtained prestudy day 2 day 8 day 15 day 22 and at surgery
Biologic markers to be assessed Docetaxel Taxotere may produce a therapeutic response by induction of programmed cell death or by inhibition of cell division Hence apoptosis by TUNEL assay and other regulatory molecules p53 bcl-2 and bax will be measured Proliferation will be assessed by measuring Ki67 From animal models antiangiogenic effects with docetaxel Taxotere have been described and this would be assessed in these clinical samples by measuring VEGF and microvessel counting CD31 Remaining frozen tissue will be snap frozen and stored temporarily in liquid nitrogen for microarray analysis
Side effects with chemotherapy are part of standard of care The chemotherapy treatments used in this protocol have all been widely used in breast cancer patients and represent some of the most effective treatments for this condition Some known effects for all chemotherapy include neutropenia infections anemia cardiotoxicity congestive heart failure alopecia nail discoloration nausea vomiting fatigue and loss of appetite
Side effects from core biopsies Risks associated with breast biopsy include bleeding bruising mild discomfort and infection Discomfort and minor complications from the four additional biopsy procedures will be minimized by use of experienced personnel
To this end we undertook a Phase II clinical trial of neoadjuvant docetaxel Taxotere in patients with locally advanced breast cancer H-8448 with the primary goal of defining the clinical efficacy and the biologic effects of docetaxel The secondary aim of the study was to identify distinctive gene expression patterns predictive of response to docetaxel chemotherapy For this we proposed to use microarray expression technology Affymetrix U95A and allied validation technologies eg IHC western blot quantitative RT-PCR to identify and validate patterns of gene expression associated with chemotherapy sensitivity or resistance
The purpose of this Phase II extension study is to determine the biologic effects of docetaxel Taxotere to identify gene expression profiles predictive of response and to further describe the efficacy of Taxotere in women with locally advanced breast cancer In addition to surgical operability and clinical response the endpoints will include the comparison of histologic and molecular markers from sequential core biopsies of primary breast cancers of patients receiving Taxotere Expression arrays will be used to identify and validate patterns of gene expression associated with Taxotere sensitivity or resistance
Clinical study A diagnostic core biopsy will be performed prestudy and tissue obtained from this will be available for analysis Other required baseline investigations including CBC kidney function tests liver function tests EKG and pregnancy tests are part of the standard of care Docetaxel Taxotere 100 mgm2 is to be administered on day 1 A core biopsy is to be performed one day after chemotherapy day 2 and on days 8 15 and 22 On day 22 after repeat core biopsy a second cycle of docetaxel Taxotere chemotherapy 100 mgm2 will be given Docetaxel Taxotere will be given three-weekly for a total of four cycles Primary surgery will then be conducted if operable following completion of neoadjuvant treatment Adjuvant AC doxorubicin 60 mgm2 and cyclophosphamide 600 mgm2 every three weeks for four cycles will then be administered Adjuvant radiotherapy will be considered following completion of AC chemotherapy Patients whose tumors were ER andor PgR positive would be commenced on tamoxifen for five years after completion of AC chemotherapy
Core biopsies Core biopsies for biologic marker evaluation will be performed prestudy excess from diagnostic biopsy and on days 2 8 15 and 22 following entry into study Tissue for analysis will also be obtained at surgery Prestudy biopsy and specimen at surgery will be part of standard of care while four additional biopsies will be performed solely for research purposes only Thus a total of six biopsies will be obtained prestudy day 2 day 8 day 15 day 22 and at surgery
Biologic markers to be assessed Docetaxel Taxotere may produce a therapeutic response by induction of programmed cell death or by inhibition of cell division Hence apoptosis by TUNEL assay and other regulatory molecules p53 bcl-2 and bax will be measured Proliferation will be assessed by measuring Ki67 From animal models antiangiogenic effects with docetaxel Taxotere have been described and this would be assessed in these clinical samples by measuring VEGF and microvessel counting CD31 Remaining frozen tissue will be snap frozen and stored temporarily in liquid nitrogen for microarray analysis
Side effects with chemotherapy are part of standard of care The chemotherapy treatments used in this protocol have all been widely used in breast cancer patients and represent some of the most effective treatments for this condition Some known effects for all chemotherapy include neutropenia infections anemia cardiotoxicity congestive heart failure alopecia nail discoloration nausea vomiting fatigue and loss of appetite
Side effects from core biopsies Risks associated with breast biopsy include bleeding bruising mild discomfort and infection Discomfort and minor complications from the four additional biopsy procedures will be minimized by use of experienced personnel
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