Ignite Creation Date:
2024-05-06 @ 9:54 AM
Last Modification Date:
2024-10-26 @ 12:21 PM
Study NCT ID:
NCT03101748
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-06-03
First Post:
2017-03-30
Brief Title:
Neratinib and Paclitaxel With or Without Pertuzumab and Trastuzumab Before Combination Chemotherapy in Treating Patients With Metastatic or Locally Advanced Breast Cancer
Sponsor:
MD Anderson Cancer Center
Organization:
MD Anderson Cancer Center
Study Overview
Official Title:
A Phase 1b Study of Neratinib Pertuzumab and Trastuzumab With Taxol 3HT in Metastatic and Locally Advanced Breast Cancer and Phase II Study of 3HT Followed by AC in HER2 Primary IBC and Neratinib With Taxol NT Followed by AC in HR HER2- Primary IBC
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-05
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:
This phase III trial studies the side effect and best dose of neratinib and to see how well it works with paclitaxel and with or without pertuzumab and trastuzumab before combination chemotherapy in treating patients with breast cancer that has spread to other places in the body metastatic Neratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Immunotherapy with pertuzumab and trastuzumab may induce changes in bodys immune system and may interfere with the ability of tumor cells to grow and spread Drugs used in chemotherapy such as paclitaxel doxorubicin and cyclophosphamide work in different ways to stop the growth of tumor cells either by killing the cells by stopping them from dividing or by stopping them from spreading Giving neratinib pertuzumab trastuzumab paclitaxel and combination chemotherapy may work better in treating patients with breast cancer
Detailed Description:
PRIMARY OBJECTIVES
I To determine the maximum tolerated dose MTD of neratinib in combination with paclitaxel pertuzumab and trastuzumab in HER2-positive HER2 metastatic or locally advanced stage III breast cancer within 2 cycles Cohort 1 Phase Ib II To determine the pathologic complete response pCR rate of neratinib in combination with paclitaxel pertuzumab and trastuzumab followed by doxorubicin and cyclophosphamide AC in HER2 metastatic or locally advanced stage III inflammatory breast cancer IBC patients Cohort 1 Phase II III To determine the pCR rate of neratinib in combination with paclitaxel followed by AC in HER2-negativehormone receptor HR-positive HER2-HR metastatic or locally advanced stage III IBC patients Cohort 2
SECONDARY OBJECTIVES
I To estimate 2 years progression free survival PFS rate of HER2 metastatic or locally advanced stage III IBC patients and HER2-HR IBC patients treated with neratinib plus anthracycline and taxane based chemotherapy Cohort I Phase II and Cohort II II To determine toxicity and safety of the combination therapy
EXPLORATORY OBJECTIVES
I To determine the adaptive target and downstream changes in pan-HER family members induced by one-week window period of neratinib based on tissue and blood based biomarkers
II To determine the correlation between positivenegative changes in EGFR HER2 and HER4 and the occurrence of pCR
III To determine the rate of HER2 mutation in HER2 IBC and HER2-HR IBC IV To determine the association between HER2 mutation and pCR achieved by study combination therapy
V To determine the correlation between tumor tissue based pharmacodynamic marker changes in association with circulating tumor cells CTC and circulating tumor deoxyribonucleic acid ctDNA
OUTLINE This is a phase I dose-escalation study of neratinib followed by a phase II study Patients are assigned to 1 of 3 groups
GROUP A COHORT 1 PHASE IB Patients receive neratinib orally PO once daily QD on days 1-21 paclitaxel intravenously IV over 1-3 hours on days 1 8 and 15 pertuzumab IV over 1 hour on day 1 and trastuzumab IV over 1-2 hours on day 1 Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity Patients without progression or excessive toxicity with metastatic disease may receive up to 4 additional courses and with locally advanced disease may receive up to 2 additional courses
GROUP B COHORT 1 PHASE II Patients receive neratinib paclitaxel pertuzumab and trastuzumab as in Group A Patients then receive doxorubicin IV and cyclophosphamide IV over 90 minutes on day 1 Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity Patients then undergo standard of care surgery
GROUP C COHORT 2 Patients receive neratinib PO QD on days 1-21 paclitaxel IV over 1-3 hours on days 1 8 and 15 Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity Patients then undergo surgery Patients then receive doxorubicin and cyclophosphamide as in Group B Patients then undergo standard of care surgery
After completion of study treatment patients are followed up at 1 month
I To determine the maximum tolerated dose MTD of neratinib in combination with paclitaxel pertuzumab and trastuzumab in HER2-positive HER2 metastatic or locally advanced stage III breast cancer within 2 cycles Cohort 1 Phase Ib II To determine the pathologic complete response pCR rate of neratinib in combination with paclitaxel pertuzumab and trastuzumab followed by doxorubicin and cyclophosphamide AC in HER2 metastatic or locally advanced stage III inflammatory breast cancer IBC patients Cohort 1 Phase II III To determine the pCR rate of neratinib in combination with paclitaxel followed by AC in HER2-negativehormone receptor HR-positive HER2-HR metastatic or locally advanced stage III IBC patients Cohort 2
SECONDARY OBJECTIVES
I To estimate 2 years progression free survival PFS rate of HER2 metastatic or locally advanced stage III IBC patients and HER2-HR IBC patients treated with neratinib plus anthracycline and taxane based chemotherapy Cohort I Phase II and Cohort II II To determine toxicity and safety of the combination therapy
EXPLORATORY OBJECTIVES
I To determine the adaptive target and downstream changes in pan-HER family members induced by one-week window period of neratinib based on tissue and blood based biomarkers
II To determine the correlation between positivenegative changes in EGFR HER2 and HER4 and the occurrence of pCR
III To determine the rate of HER2 mutation in HER2 IBC and HER2-HR IBC IV To determine the association between HER2 mutation and pCR achieved by study combination therapy
V To determine the correlation between tumor tissue based pharmacodynamic marker changes in association with circulating tumor cells CTC and circulating tumor deoxyribonucleic acid ctDNA
OUTLINE This is a phase I dose-escalation study of neratinib followed by a phase II study Patients are assigned to 1 of 3 groups
GROUP A COHORT 1 PHASE IB Patients receive neratinib orally PO once daily QD on days 1-21 paclitaxel intravenously IV over 1-3 hours on days 1 8 and 15 pertuzumab IV over 1 hour on day 1 and trastuzumab IV over 1-2 hours on day 1 Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity Patients without progression or excessive toxicity with metastatic disease may receive up to 4 additional courses and with locally advanced disease may receive up to 2 additional courses
GROUP B COHORT 1 PHASE II Patients receive neratinib paclitaxel pertuzumab and trastuzumab as in Group A Patients then receive doxorubicin IV and cyclophosphamide IV over 90 minutes on day 1 Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity Patients then undergo standard of care surgery
GROUP C COHORT 2 Patients receive neratinib PO QD on days 1-21 paclitaxel IV over 1-3 hours on days 1 8 and 15 Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity Patients then undergo surgery Patients then receive doxorubicin and cyclophosphamide as in Group B Patients then undergo standard of care surgery
After completion of study treatment patients are followed up at 1 month
Study Oversight
Has Oversight DMC:
None
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?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2016-0537 | OTHER | M D Anderson Cancer Center | None |
| NCI-2017-00813 | REGISTRY | None | None |