Doxorubicin and Cyclophosphamide Followed By Trastuzumab, Paclitaxel, and Lapatinib in Treating Patients With Early-Stage HER2-Positive Breast Cancer That Has Been Removed By Surgery
RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with trastuzumab and lapatinib after surgery may kill any tumor cells that remain after surgery.
PURPOSE: This randomized phase II trial is studying the side effects and how well giving doxorubicin together with cyclophosphamide followed by trastuzumab, paclitaxel, and lapatinib works in treating patients with early-stage HER2-positive breast cancer that has been removed by surgery.
Drug: doxorubicin hydrochloride
Drug: lapatinib ditosylate
Genetic: gene expression analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: laboratory biomarker analysis
Other: mass spectrometry
Procedure: adjuvant therapy
Procedure: quality-of-life assessment
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||Phase II Study of Cardiac Safety and Tolerability of an Adjuvant Chemotherapy Plus Trastuzumab With Lapatinib in Patients With Resected HER2 + Breast Cancer|
- Number of Patients With Congestive Heart Failure (CHF) While on Active Treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Adverse Event Profile as Measured by NCI CTCAE v 3.0 [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]Maximum grade for each type of adverse event will be recorded for each patient.
- Cumulative Incidence (CI) of Cardiac Events [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Evaluable patients included those completed the AC phase of their treatment regimen; with post AC cardiac evaluation indicates they are eligible to begin treatment with PTL; and those have begun their post-AC therapy.
Cardiac events: symptomatic congestive heart failure (CHF), cardiac death and other cardiac events (NCI Common Terminology Criteria for Adverse Events (CTCAE) Grade >=3)
- Number of Patients Who Experience >= 10 Percent Drop in Left Ventricular Ejection Fraction (LVEF) Between Two Time Points [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Disease-free Survival (DFS) [ Time Frame: 5 years ] [ Designated as safety issue: No ]DFS was defined as the time from registration to the earliest date of documentation of any local, regional, or distant recurrence of breast cancer (BC); the development of a contralateral BC or second primary other than squamous or basal cell carcinoma of the skin, carcinoma in situ of the cervix, or lobular carcinoma in situ of the breast; or death from any cause without the documentation of one of these events. Participants were followed for a maximum of 5 years from randomization. The median OS with 95%CI was estimated using the Kaplan Meier method.
- Overall Survival (OS) [ Time Frame: 5 years ] [ Designated as safety issue: No ]OS was defined as the time from registration to death of any cause. Participants were followed for a maximum of 5 years from randomization. The median OS with 95%CI was estimated using the Kaplan Meier method.
- Comparison of Selected Quality-of-life Questionnaires [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Quality-of-life [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Incidence of Pulmonary Events [ Time Frame: 5 years ] [ Designated as safety issue: No ]Pulmonary events to be included were grade 3 and higher pulmonary adverse events at least possibly related to study treatment, which occur at any time after post-AC treatment is begun, but prior to documentation of a breast cancer recurrence, contralateral breast cancer, secondary primary cancer, non-pulmonary death, or pulmonary death not related to study treatment.
|Study Start Date:||March 2007|
|Primary Completion Date:||April 2009 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00436566
|United States, Minnesota|
|Mayo Clinic Cancer Research Consortium|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Edith A. Perez, MD||Mayo Clinic in Florida|
|Principal Investigator:||Donald W. Northfeld, MD||Mayo Clinic in Arizona|
|Principal Investigator:||James N. Ingle, MD||Mayo Clinic in Rochester|