Doxorubicin and Cyclophosphamide Followed by Paclitaxel, Trastuzumab, and Lapatinib in Treating Patients With HER2/Neu-Overexpressed Breast Cancer - Full Text View

Purpose

The purpose of this study is to study a new treatment for HER-2/neu (+) breast cancer.

Condition	Intervention	Phase
Breast Cancer	Biological: trastuzumab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: lapatinib ditosylate Drug: paclitaxel Other: laboratory biomarker analysis	Phase 2


Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: No masking Primary Purpose: Treatment
Official Title:	Phase II Study of Dose-Dense Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel With Trastuzumab and Lapatinib in HER2/NEU-Overexpressed/Amplified Breast Cancer: Feasibility

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer

Drug Information available for: Cyclophosphamide Doxorubicin Doxorubicin hydrochloride Paclitaxel Trastuzumab Lapatinib Lapatinib Ditosylate

Genetic and Rare Diseases Information Center resources: Breast Cancer, Male

U.S. FDA Resources

Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:

Number of Patients Who Completed All Planned Therapy [ Time Frame: 2 years ]
The number of patients who completed all planned therapy (dose-dense adjuvant/ neoadjuvant chemotherapy regimen) in HER-2/neu-overexpressed/ amplified breast cancer patients.

Secondary Outcome Measures:

Number of Patients Who Were Evaluated for Toxicity [ Time Frame: 2 years ]
Please see adverse event section in the results. Toxicities were assessed by the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 3.0.


Enrollment:	95
Study Start Date:	March 2007
Study Completion Date:	July 2011
Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB The regimen consists of AC (doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2) q 14 days x 4 with pegfilgrastim, followed by weekly paclitaxel (80 mg/m2) x 12 + trastuzumab (H) + lapatinib (L). Pegfilgrastim 6mg is given subcutaneously (SQ) on day # 2 of each AC. Filgrastim may be used in lieu of pegfilgrastim at the physician's discretion. Trastuzumab will be administered weekly starting with paclitaxel treatment # 1. Near the completion of all chemotherapy, patients may receive trastuzumab on a q 3-weekly schedule, starting as early as with paclitaxel cycle # 12. The total duration of trastuzumab from beginning to end is 52 weeks. Lapatinib will be given orally at 1000 mg daily, starting with trastuzumab for a total duration of 52 weeks. Hormonal therapy such as tamoxifen or an aromatase inhibitor will be given to patients with hormone receptor positive disease at the physician's discretion. Radiation therapy to the breast or chest is recommended to patients as appropriate.	Biological: trastuzumab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: lapatinib ditosylate Drug: paclitaxel Other: laboratory biomarker analysis

Arms

Assigned Interventions

Experimental: AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB

The regimen consists of AC (doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2) q 14 days x 4 with pegfilgrastim, followed by weekly paclitaxel (80 mg/m2) x 12 + trastuzumab (H) + lapatinib (L). Pegfilgrastim 6mg is given subcutaneously (SQ) on day # 2 of each AC. Filgrastim may be used in lieu of pegfilgrastim at the physician's discretion. Trastuzumab will be administered weekly starting with paclitaxel treatment # 1. Near the completion of all chemotherapy, patients may receive trastuzumab on a q 3-weekly schedule, starting as early as with paclitaxel cycle # 12. The total duration of trastuzumab from beginning to end is 52 weeks. Lapatinib will be given orally at 1000 mg daily, starting with trastuzumab for a total duration of 52 weeks. Hormonal therapy such as tamoxifen or an aromatase inhibitor will be given to patients with hormone receptor positive disease at the physician's discretion. Radiation therapy to the breast or chest is recommended to patients as appropriate.

Biological: trastuzumab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: lapatinib ditosylate Drug: paclitaxel Other: laboratory biomarker analysis

Eligibility


Ages Eligible for Study:	18 Years to 120 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the breast
- Bilateral synchronous breast tumors allowed
- Any nodal status or tumor size allowed
  - No stage IV disease
HER2/neu-positive disease
- 3+ by IHC OR FISH-amplified
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Male or female
Menopausal status not specified
ECOG performance status 0-1
Absolute neutrophil count ≥ 1,000/mm³
Platelet count ≥ 100,000/mm³
Bilirubin ≤ 1.1 mg/dL
SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and after completion of study therapy
LVEF ≥ 50% by MUGA scan
No peripheral neuropathy > grade 1
No active second malignancy within the past 5 years except for adequately treated nonmelanoma skin cancer or in situ carcinoma of the cervix
No known allergy or hypersensitivity to doxorubicin hydrochloride, cyclophosphamide, paclitaxel, or other drugs formulated in Cremophor EL
No psychiatric illness or concurrent medical conditions that would preclude study treatment
No other conditions, including any of the following:
- Unstable angina
- Congestive heart failure
- Myocardial infarction within the past 12 months
- High-risk uncontrolled arrhythmias (e.g., ventricular tachycardia, high-grade AV block, or supraventricular arrhythmias that are not adequately controlled)
No QT prolongation (> 500 ms)
No active unresolved infections
No sensitivity to E. coli derived proteins

PRIOR CONCURRENT THERAPY:

Prior hormonal therapy for chemoprevention allowed
No prior trastuzumab (Herceptin®)
No prior anthracyclines
No concurrent hormonal therapy, including hormonal contraception (e.g., birth control pills or ovarian hormonal or replacement therapy)
No other concurrent chemotherapy, radiotherapy, immunotherapy, or biotherapy for breast cancer
No concurrent drugs that may prolong the QT

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00482391

Locations


United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

National Cancer Institute (NCI)

Dana-Farber Cancer Institute

GlaxoSmithKline

Investigators


Principal Investigator:	Chau T. Dang, MD	Memorial Sloan Kettering Cancer Center
Principal Investigator:	Clifford A. Hudis, MD	Memorial Sloan Kettering Cancer Center

More Information

Publications:

Dang C, Lin N, Moy B, Come S, Sugarman S, Morris P, Abbruzzi A, Chen C, Steingart R, Patil S, Norton L, Winer E, Hudis C. Dose-dense doxorubicin and cyclophosphamide followed by weekly paclitaxel with trastuzumab and lapatinib in HER2/neu-overexpressed/amplified breast cancer is not feasible because of excessive diarrhea. J Clin Oncol. 2010 Jun 20;28(18):2982-8. doi: 10.1200/JCO.2009.26.5900. Epub 2010 May 17. Erratum in: J Clin Oncol. 2010 Aug 1;28(22):3670.


Responsible Party:	Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00482391 History of Changes
Other Study ID Numbers:	07-013 MSKCC-07013
Study First Received:	June 4, 2007
Results First Received:	December 22, 2015
Last Updated:	April 6, 2017

Keywords provided by Memorial Sloan Kettering Cancer Center:


recurrent breast cancer stage I breast cancer stage II breast cancer stage IIIA breast cancer	stage IIIB breast cancer stage IIIC breast cancer male breast cancer

Additional relevant MeSH terms:


Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Paclitaxel Liposomal doxorubicin Lapatinib Albumin-Bound Paclitaxel Doxorubicin Trastuzumab Cyclophosphamide Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators	Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Myeloablative Agonists Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on June 27, 2017