Paclitaxel and Trastuzumab and/or Lapatinib in Treating Patients With Stage II or Stage III Breast Cancer That Can Be Removed by Surgery - Full Text View

Sponsor:	Cancer and Leukemia Group B
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00770809

Purpose

RATIONALE: Drugs used in chemotherapy, such as 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 paclitaxel together with trastuzumab and/or lapatinib before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known which regimen is more effective in treating patients with breast cancer.

PURPOSE: This randomized phase III trial is studying paclitaxel to see how well it works when given together with trastuzumab and/or lapatinib in treating patients with stage II or stage III breast cancer that can be removed by surgery.

Condition	Intervention	Phase
Breast Cancer	Biological: trastuzumab Drug: lapatinib ditosylate Drug: paclitaxel	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Randomized Phase III Trial of Paclitaxel Combined With Trastuzumab, Lapatinib, or Both as Neoadjuvant Treatment of Her2-Positive Primary Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Surgery

Drug Information available for: Paclitaxel Trastuzumab Lapatinib Lapatinib Ditosylate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Pathologic complete response in the breast [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pathologic stage in the breast and axilla as defined by AJCC TNM v6.0 criteria [ Designated as safety issue: No ]
Clinical response at the completion of neoadjuvant therapy [ Designated as safety issue: No ]
Radiographic response at the completion of neoadjuvant therapy [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Invasive disease-free survival [ Designated as safety issue: No ]
Time to first failure [ Designated as safety issue: No ]
Toxicity as defined by NCI CTCAE v3.0 criteria [ Designated as safety issue: Yes ]

Estimated Enrollment:	400
Study Start Date:	December 2008
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes and paclitaxel IV over 1 hour once weekly and oral lapatinib ditosylate once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.	Biological: trastuzumab Given IV Drug: lapatinib ditosylate Given orally Drug: paclitaxel Given IV
Arm II: Active Comparator Patients receive trastuzumab and paclitaxel as in arm I.	Biological: trastuzumab Given IV Drug: paclitaxel Given IV
Arm III: Experimental Patients receive paclitaxel and lapatinib ditosylate as in arm I.	Drug: lapatinib ditosylate Given orally Drug: paclitaxel Given IV

Detailed Description:

OBJECTIVES:

Primary

To compare the pathologic complete response (pCR) in the breast of patients with HER2-positive resectable stage II or III breast cancer treated with neoadjuvant paclitaxel in combination with trastuzumab (Herceptin®) and/or lapatinib ditosylate.

Secondary

To compare the pCR in the breast and axilla of these patients.
To evaluate residual cancer burden as a predictor of long-term disease-free survival and overall survival of these patients.
To document the toxicity of these regimens in these patients.
To determine the correlation between clinical, radiographic, and pathologic response in these patients.
To compare overall survival, invasive disease-free survival, and time to first failure in these patients.
To evaluate biomarkers in tissue samples that are likely to influence response to and toxicity of these regimens.
To determine the surgical practice patterns for breast conservation and sentinel lymphadenectomy in patients undergoing neoadjuvant chemotherapy.

OUTLINE: This is a multicenter study. Patients are stratified according to pretreatment clinical stage (II vs III) and hormone receptor status (estrogen receptor [ER]- and/or progesterone receptor [PR]-positive vs ER- and PR-negative). Patients are randomized to 1 of 3 treatment arms.

Arm I: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes and paclitaxel IV over 1 hour once weekly and oral lapatinib ditosylate once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.
Arm II: Patients receive trastuzumab and paclitaxel as in arm I.
Arm III: Patients receive paclitaxel and lapatinib ditosylate as in arm I. Within 42 days after completion of neoadjuvant therapy, patients in all arms undergo definitive surgery (breast conservation or total mastectomy). Patients may then receive adjuvant therapy (e.g., radiotherapy, hormonal therapy, and/or additional chemotherapy and trastuzumab) at the discretion of the treating physician.

Tumor tissue samples are collected at baseline for correlative laboratory studies. Samples are analyzed for biomarkers (e.g., HER2, IGF1R, Ki67, apoptosis, PIK3CA, PTEN, Topo II, c-myc, EGFR, HER3, HER4, 2CF, Erk 1/2, AKT, and other biomarkers) by quantitative RT-PCR, IHC, TUNEL assay, FISH, gene expression array, and comparative genomic hybridization.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually for up to 10 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Pathologically confirmed invasive breast cancer by core needle or incisional biopsy
- Clinical stage II or III disease
- Resectable disease
HER2-positive tumor, defined as 3+ overexpression by IHC or gene amplification by FISH with a ratio of ≥ 2 on invasive tumor
Measurable disease, defined as target lesion in the breast ≥ 1 cm by physical examination or radiographic measurement
- No axillary disease only
Multicentric or bilateral disease allowed provided the target lesion meets eligibility criteria
Planning to undergo surgical resection after neoadjuvant therapy
No inflammatory breast cancer
No metastatic disease
Concurrent enrollment in CALGB-150702 required
Hormone receptor status known

PATIENT CHARACTERISTICS:

Menopausal status not specified
ECOG (Zubrod) performance status 0-1
ANC ≥ 1,000/mm³
Platelet count ≥ 100,000/mm³
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective non-hormonal contraception during and for ≥ 2 months after completion of study treatment
Cardiac ejection fraction ≥ 50% by echocardiogram or MUGA scan
Willing to undergo pretreatment biopsies and submit archival tissue obtained at the time of surgery

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior chemotherapy, hormonal therapy, biologic therapy, or radiotherapy for the treatment of breast cancer
No other concurrent chemotherapy or hormonal therapy, except for the following:
- Steroids for adrenal failure
- Hormones for non-disease-related conditions (e.g., insulin for diabetes)
- Intermittent use of dexamethasone as an antiemetic
No concurrent pegfilgrastim

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00770809

Show 103 Study Locations

Sponsors and Collaborators

Cancer and Leukemia Group B

National Cancer Institute (NCI)

Investigators

Study Chair:

Lisa A. Carey, MD

UNC Lineberger Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Cancer and Leukemia Group B ( Richard L. Schilsky )
Study ID Numbers:	CDR0000616648, CALGB-40601
Study First Received:	October 9, 2008
Last Updated:	February 5, 2010
ClinicalTrials.gov Identifier:	NCT00770809 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

male breast cancer
stage II breast cancer
stage IIIA breast cancer

stage IIIB breast cancer
stage IIIC breast cancer
HER2-positive breast cancer

Additional relevant MeSH terms:

Skin Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Breast Neoplasms
Enzyme Inhibitors
Lapatinib
Antimitotic Agents
Protein Kinase Inhibitors

Pharmacologic Actions
Neoplasms
Neoplasms by Site
Paclitaxel
Therapeutic Uses
Tubulin Modulators
Trastuzumab
Antineoplastic Agents, Phytogenic
Breast Diseases

ClinicalTrials.gov processed this record on February 08, 2010