Ignite Creation Date:
2024-05-05 @ 5:26 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00450892
Status:
COMPLETED
Last Update Posted:
2016-07-07
First Post:
2007-03-20
Brief Title:
Phase III Study of Neoadjuvant Lapatinib in Breast Cancer
Sponsor:
European Organisation for Research and Treatment of Cancer - EORTC
Organization:
European Organisation for Research and Treatment of Cancer - EORTC
Study Overview
Official Title:
A Phase I-II Study of Lapatinib and Docetaxel as Neoadjuvant Treatment for HER-2 Positive Locally AdvancedInflammatory or Large Operable Breast Cancer
Status:
COMPLETED
Status Verified Date:
2016-07
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:
RATIONALE Drugs used in chemotherapy such as docetaxel fluorouracil epirubicin and cyclophosphamide work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth Monoclonal antibodies such as trastuzumab can block tumor growth in different ways Some block the ability of tumor cells to grow and spread Others find tumor cells and help kill them or carry tumor-killing substances to them Giving these treatments before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed Giving trastuzumab after surgery may kill any tumor cells that remain after surgery
PURPOSE This randomized phase III trial is studying the side effects and best dose of docetaxel and lapatinib when given with or without combination chemotherapy and to see how well they work in treating women with locally advanced inflammatory or resectable breast cancer
PURPOSE This randomized phase III trial is studying the side effects and best dose of docetaxel and lapatinib when given with or without combination chemotherapy and to see how well they work in treating women with locally advanced inflammatory or resectable breast cancer
Detailed Description:
OBJECTIVES
Primary
Determine the maximum tolerated dose of neoadjuvant therapy comprising docetaxel and lapatinib ditosylate before or after fluorouracil epirubicin hydrochloride and cyclophosphamide FEC chemotherapy in patients with HER2-positive locally advanced inflammatory or large resectable breast cancer Phase I
Determine the safety of this regimen in these patients Phase I
Determine the pathological complete response rate in patients treated with neoadjuvant docetaxel and lapatinib ditosylate followed by FEC chemotherapy and with neoadjuvant docetaxel and trastuzumab Herceptin followed by FEC chemotherapy Phase II
Secondary
Determine the biological activity ie changes in apoptosis and proliferation markers PTEN mutation and function pAkt mTOR and associated proteins of neoadjuvant docetaxel and lapatinib ditosylate in these patients Phase I
Determine adverse events or biological modifications Phase I
Determine the tolerability of these regimens in these patients Phase II
Determine the clinical activity of these regimens Phase II
Identify genes that may predict response in patients treated with docetaxel and lapatinib ditosylate Phase II
OUTLINE This is a multicenter open-label phase I dose-escalation study of docetaxel and lapatinib ditosylate followed by a randomized phase II study Patients enrolled in the phase II portion of the study are stratified by institution and disease status locally advanced disease vs large operable tumor
Phase I completed as of 5262010 Patients receive docetaxel IV over 1 hour on day 1 and oral lapatinib ditosylate once daily on days 1-21 Treatment repeats every 3 weeks for 4 courses Two additional courses may be given at the discretion of the physician
Cohorts of 3-6 patients receive escalating doses of docetaxel and lapatinib ditosylate until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity DLT
Phase I bridge step completed as of 5262010 Patients receive FEC chemotherapy comprising fluorouracil IV over 15 minutes epirubicin hydrochloride IV over 60 minutes and cyclophosphamide IV over 60 minutes on day 1 Treatment repeats every 3 weeks for 3 courses Patients also receive docetaxel and lapatinib ditosylate as in phase I at the MTD for up to 3 courses
Cohorts of 3-6 patients receive de-escalating doses of docetaxel and lapatinib ditosylate in combination with FEC chemotherapy until the MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT
Phase II Patients are randomized to 1 of 3 treatment arms
Arm I Patients receive docetaxel and lapatinib ditosylate at the MTD as in the bridge step of phase I followed by FEC chemotherapy
Arm II Patients receive docetaxel IV over 60 minutes and trastuzumab Herceptin IV over 30-90 minutes on days 1 8 and 15 Patients then receive FEC chemotherapy as in the bridge step of phase I Treatment with docetaxel and trastuzumab repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity
Arm III Patients receive docetaxel IV over 60 minutes lapatinib ditosylate at the MTD as in the bridge step of phase I and trastuzumab Herceptin IV over 30-90 minutes on days 1 8 and 15 Patients then receive FEC chemotherapy as in the bridge step of phase I Treatment with docetaxel lapatinib ditosylate and trastuzumab repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity
All patients then undergo surgery to remove the tumor Patients may then receive trastuzumab every 3 weeks for 1 year
Blood samples are collected at baseline and periodically during study for pharmacokinetic studies Patients also undergo tumor biopsies at baseline and periodically during study for laboratory studies Blood and tissue samples are analyzed by quantitative reverse transcriptase polymerase chain reaction for biomarker profiling HER1-3 Akt 1-3 mTOR RICTOR RAPTOR CCND1 p21 survivin PTEN immunohistochemistry fluorescent in situ hybridization TopoII HER2 and proteomics
After completion of study treatment patients are followed periodically
PROJECTED ACCRUAL A total of 150 patients will be accrued for the phase II
Primary
Determine the maximum tolerated dose of neoadjuvant therapy comprising docetaxel and lapatinib ditosylate before or after fluorouracil epirubicin hydrochloride and cyclophosphamide FEC chemotherapy in patients with HER2-positive locally advanced inflammatory or large resectable breast cancer Phase I
Determine the safety of this regimen in these patients Phase I
Determine the pathological complete response rate in patients treated with neoadjuvant docetaxel and lapatinib ditosylate followed by FEC chemotherapy and with neoadjuvant docetaxel and trastuzumab Herceptin followed by FEC chemotherapy Phase II
Secondary
Determine the biological activity ie changes in apoptosis and proliferation markers PTEN mutation and function pAkt mTOR and associated proteins of neoadjuvant docetaxel and lapatinib ditosylate in these patients Phase I
Determine adverse events or biological modifications Phase I
Determine the tolerability of these regimens in these patients Phase II
Determine the clinical activity of these regimens Phase II
Identify genes that may predict response in patients treated with docetaxel and lapatinib ditosylate Phase II
OUTLINE This is a multicenter open-label phase I dose-escalation study of docetaxel and lapatinib ditosylate followed by a randomized phase II study Patients enrolled in the phase II portion of the study are stratified by institution and disease status locally advanced disease vs large operable tumor
Phase I completed as of 5262010 Patients receive docetaxel IV over 1 hour on day 1 and oral lapatinib ditosylate once daily on days 1-21 Treatment repeats every 3 weeks for 4 courses Two additional courses may be given at the discretion of the physician
Cohorts of 3-6 patients receive escalating doses of docetaxel and lapatinib ditosylate until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity DLT
Phase I bridge step completed as of 5262010 Patients receive FEC chemotherapy comprising fluorouracil IV over 15 minutes epirubicin hydrochloride IV over 60 minutes and cyclophosphamide IV over 60 minutes on day 1 Treatment repeats every 3 weeks for 3 courses Patients also receive docetaxel and lapatinib ditosylate as in phase I at the MTD for up to 3 courses
Cohorts of 3-6 patients receive de-escalating doses of docetaxel and lapatinib ditosylate in combination with FEC chemotherapy until the MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT
Phase II Patients are randomized to 1 of 3 treatment arms
Arm I Patients receive docetaxel and lapatinib ditosylate at the MTD as in the bridge step of phase I followed by FEC chemotherapy
Arm II Patients receive docetaxel IV over 60 minutes and trastuzumab Herceptin IV over 30-90 minutes on days 1 8 and 15 Patients then receive FEC chemotherapy as in the bridge step of phase I Treatment with docetaxel and trastuzumab repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity
Arm III Patients receive docetaxel IV over 60 minutes lapatinib ditosylate at the MTD as in the bridge step of phase I and trastuzumab Herceptin IV over 30-90 minutes on days 1 8 and 15 Patients then receive FEC chemotherapy as in the bridge step of phase I Treatment with docetaxel lapatinib ditosylate and trastuzumab repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity
All patients then undergo surgery to remove the tumor Patients may then receive trastuzumab every 3 weeks for 1 year
Blood samples are collected at baseline and periodically during study for pharmacokinetic studies Patients also undergo tumor biopsies at baseline and periodically during study for laboratory studies Blood and tissue samples are analyzed by quantitative reverse transcriptase polymerase chain reaction for biomarker profiling HER1-3 Akt 1-3 mTOR RICTOR RAPTOR CCND1 p21 survivin PTEN immunohistochemistry fluorescent in situ hybridization TopoII HER2 and proteomics
After completion of study treatment patients are followed periodically
PROJECTED ACCRUAL A total of 150 patients will be accrued for the phase II
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 |
|---|---|---|---|
| EORTC-10054 | None | None | None |
| 2006-000864-94 | EUDRACT_NUMBER | None | None |
| GSK-EORTC-10054 | None | None | None |