Clinical trial · Interventional

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

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

NCT00482391CI-TRIAL-00027545completedPhase 2Results postedClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Breast Cancer	Malignant Breast Neoplasm	CURATED_EXACT	0.92

Interventions

Interventions (6)

Intervention	Type	Mapped drug	Match
cyclophosphamide	Drug	Cyclophosphamide	ALIAS
doxorubicin hydrochloride	Drug	Doxorubicin	ALIAS
laboratory biomarker analysis	Other	—	UNRESOLVED
lapatinib ditosylate	Drug	Lapatinib	ALIAS
paclitaxel	Drug	Paclitaxel	ALIAS
trastuzumab	Biological	Trastuzumab	ALIAS

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB
description
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.
interventionNames
1. Biological: trastuzumab
2. Drug: cyclophosphamide
3. Drug: doxorubicin hydrochloride
4. Drug: lapatinib ditosylate
5. Drug: paclitaxel
6. Other: laboratory biomarker analysis

Primary outcomes (1)

measure

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years
Maximum age: 120 Years

Show eligibility criteria text

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

References

Publications (1)

RESULTDang 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. PMID 20479410

Registry

Dates and enrollment

Start: Mar 1, 2007
Primary completion: Jul 1, 2011
Completion: Jul 1, 2011
First posted: Jun 5, 2007
Last update posted: May 12, 2017
Results first posted: Mar 13, 2017
Enrollment: 95 (actual)
Lead sponsor: Memorial Sloan Kettering Cancer Center OTHER
Collaborators: National Cancer Institute (NCI); Dana-Farber Cancer Institute; GlaxoSmithKline
Keywords: 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

Data updated 22 days agoSource updated May 12, 2017source: clinicaltrials

Locations

Locations by country (2)

Country	Sites	Recruiting
United States	2	0

Trial listing is informational. Eligibility is decided by the study team; contact information is on ClinicalTrials.gov.