Ignite Creation Date:
2025-12-24 @ 6:58 PM
Ignite Modification Date:
2025-12-27 @ 7:34 PM
Study NCT ID:
NCT02456857
Status:
COMPLETED
Last Update Posted:
2024-02-13
First Post:
2015-05-27
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Liposomal Doxorubicin, Bevacizumab, and Everolimus in Patients With Locally Advanced TNBC With Tumors Predicted Insensitive to Standard Chemotherapy; A Moonshot Initiative
Sponsor:
M.D. Anderson Cancer Center
Organization:
Study Overview
Official Title:
Women's Triple-Negative First-Line Study: A Phase II Trial of Liposomal Doxorubicin, Bevacizumab and Everolimus (DAE) in Patients With Localized Triple-Negative Breast Cancer (TNBC) With Tumors Predicted Insensitive to Standard Neoadjuvant Chemotherapy
Status:
COMPLETED
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase II trial studies how well pegylated liposomal doxorubicin, bevacizumab, and everolimus work in treating patients with triple-negative breast cancer with tumors predicted insensitive to standard chemotherapy. Drugs used in chemotherapy, such as pegylated liposomal doxorubicin, work in different ways to stop the growth of tumor cells by stopping them from dividing. Bevacizumab may stop or slow breast cancer by blocking the growth of new blood vessels necessary for tumor growth. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pegylated liposomal doxorubicin together with bevacizumab and everolimus may kill more tumor cells.
Detailed Description:
PRIMARY OBJECTIVE:
I. Determine excellent clinical response rates (pathologic complete response \[pCR\]/residual cancer burden \[RCB\]-0 or minimal residual disease \[RCB-I\]) in patients with anthracycline-based chemotherapy insensitive, localized triple-negative breast cancer (TNBC) who receive 4 cycles of pegylated liposomal doxorubicin hydrochloride, bevacizumab, and everolimus (DAE) following anthracycline-based chemotherapy in the neoadjuvant setting.
SECONDARY OBJECTIVES:
I. Determine response rate after 4 cycles of DAE using radiographic imaging. II. Determine toxicity associated 4 cycles of DAE in the neoadjuvant setting. III. Pathologic response rates to 4 cycles of DAE in mesenchymal tumors versus (vs.) non-mesenchymal tumors.
V. Compare pathologic response rates in mesenchymal tumors to 4 cycles of DAE vs. 12 weeks of weekly paclitaxel (using data collected from standard of care treatment).
EXPLORATORY OBJECTIVES:
I. Determine the correlation between vimentin expression by immunohistochemistry (IHC) and the presence of mesenchymal gene signatures at the time of initial tumor biopsy prior to neoadjuvant chemotherapy (NACT).
II. Determine the correlation between mutations in PIK3CA, PTEN or NF2 or PTEN loss by IHC and the presence of mesenchymal gene signatures at the time of initial tumor biopsy prior to NACT.
III. Determine rates of pCR in patients with mesenchymal tumors identified by gene signatures and compare to pCR rates in non-mesenchymal tumors.
IV. Correlate pathologic response with degree of vimentin expression as measured by IHC.
V. Determine rates of pCR in patients whose tumors contain mutations in PIK3CA, PTEN or NF2 or PTEN loss by IHC and compare to pCR rates in patients whose tumors lacks mutations in these genes.
OUTLINE:
Patients receive pegylated liposomal doxorubicin hydrochloride intravenously (IV) over about 3 hours on day 1, bevacizumab IV over 90 minutes on day 1, and everolimus orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients will not receive bevacizumab during cycle 4 of therapy. Patients then undergo surgery.
After completion of study treatment, patients are followed up within 30 days of surgery.
I. Determine excellent clinical response rates (pathologic complete response \[pCR\]/residual cancer burden \[RCB\]-0 or minimal residual disease \[RCB-I\]) in patients with anthracycline-based chemotherapy insensitive, localized triple-negative breast cancer (TNBC) who receive 4 cycles of pegylated liposomal doxorubicin hydrochloride, bevacizumab, and everolimus (DAE) following anthracycline-based chemotherapy in the neoadjuvant setting.
SECONDARY OBJECTIVES:
I. Determine response rate after 4 cycles of DAE using radiographic imaging. II. Determine toxicity associated 4 cycles of DAE in the neoadjuvant setting. III. Pathologic response rates to 4 cycles of DAE in mesenchymal tumors versus (vs.) non-mesenchymal tumors.
V. Compare pathologic response rates in mesenchymal tumors to 4 cycles of DAE vs. 12 weeks of weekly paclitaxel (using data collected from standard of care treatment).
EXPLORATORY OBJECTIVES:
I. Determine the correlation between vimentin expression by immunohistochemistry (IHC) and the presence of mesenchymal gene signatures at the time of initial tumor biopsy prior to neoadjuvant chemotherapy (NACT).
II. Determine the correlation between mutations in PIK3CA, PTEN or NF2 or PTEN loss by IHC and the presence of mesenchymal gene signatures at the time of initial tumor biopsy prior to NACT.
III. Determine rates of pCR in patients with mesenchymal tumors identified by gene signatures and compare to pCR rates in non-mesenchymal tumors.
IV. Correlate pathologic response with degree of vimentin expression as measured by IHC.
V. Determine rates of pCR in patients whose tumors contain mutations in PIK3CA, PTEN or NF2 or PTEN loss by IHC and compare to pCR rates in patients whose tumors lacks mutations in these genes.
OUTLINE:
Patients receive pegylated liposomal doxorubicin hydrochloride intravenously (IV) over about 3 hours on day 1, bevacizumab IV over 90 minutes on day 1, and everolimus orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients will not receive bevacizumab during cycle 4 of therapy. Patients then undergo surgery.
After completion of study treatment, patients are followed up within 30 days of surgery.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: