Paclitaxel and Trastuzumab With or Without Lapatinib in Treating Patients With Stage II or Stage III Breast Cancer That Can Be Removed by Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00770809
First received: October 9, 2008
Last updated: May 7, 2014
Last verified: May 2014

October 9, 2008
May 7, 2014
December 2008
January 2014   (final data collection date for primary outcome measure)
Pathologic complete response (pCR) [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
Pathologic complete response in the breast [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00770809 on ClinicalTrials.gov Archive Site
  • Pathologic stage in the breast and axilla as defined by AJCC TNM v6.0 criteria [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
  • Clinical response at the completion of neoadjuvant therapy [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
  • Radiographic response at the completion of neoadjuvant therapy [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Measured from study entry to death due to any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
  • Relapse-free survival (RFS) [ Time Frame: From definitive surgery to ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, or death from any cause, whichever occurs first, assessed up to 10 years ] [ Designated as safety issue: No ]
  • Time to first failure [ Time Frame: From study entry to ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence or death from any cause, assessed up to 10 years ] [ Designated as safety issue: No ]
  • 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 ]
Not Provided
Not Provided
 
Paclitaxel and Trastuzumab With or Without Lapatinib in Treating Patients With Stage II or Stage III Breast Cancer That Can Be Removed by Surgery
RANDOMIZED PHASE III TRIAL OF PACLITAXEL + TRASTUZUMAB + LAPATINIB VERSUS PACLITAXEL + TRASTUZUMAB AS NEOADJUVANT TREATMENT OF HER2-POSITIVE PRIMARY BREAST CANCER

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. 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.

PRIMARY OBJECTIVE:

I. To determine if the pathologic complete response (pCR) in the breast to neoadjuvant weekly paclitaxel with trastuzumab plus lapatinib (THL) is 20% greater than the pCR to weekly paclitaxel with trastuzumab alone (TH).

SECONDARY OBJECTIVES:

I.To determine the pathologic complete response in the breast and axilla, using AJCC TMN criteria (Version 6), to neoadjuvant weekly paclitaxel plus HER2- targeted therapy in patients with HER2-positive operable breast cancer.

II. To evaluate residual cancer burden (RCB) as a predictor of long term relapse free survival (RFS) and overall survival (OS).

III. To document the toxicity of all chemotherapeutic regimens (THL, TH). IV. To determine the correlation between clinical, radiographic and pathologic response.

V. To compare overall survival (OS), relapse free survival (RFS) and time to first failure (TFF) among the treatment groups. OS and TFF will be measured for all patients from study registration. RFS will be measured from definitive surgery for those patients who undergo definitive surgery.

VI. To obtain blood, fresh frozen and fixed tumor tissue to test specific hypotheses for which biomarker data exist and to evaluate biomarkers in blood, serum and tissue that are likely to influence response to and toxicity of trastuzumab alone or trastuzumab plus lapatinib, when given with paclitaxel.

VII. To determine the surgical practice patterns for breast conservation and sentinel lymphadenectomy in patients undergoing neoadjuvant chemotherapy.

VIII. To determine the radiotherapy practice patterns for post-mastectomy and regional nodal irradiation in patients undergoing neoadjuvant chemotherapy.

IX. To evaluate pharmacogenomic determinants of toxicity.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive trastuzumab IV over 30-90 minutes and paclitaxel IV over 1 hour once weekly and lapatinib ditosylate orally (PO) 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. (Discontinued as of 6-15-11) Within 42 days after completion of neoadjuvant therapy, patients in both arms undergo definitive surgery (breast conservation or total mastectomy).

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

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HER2-positive Breast Cancer
  • Male Breast Cancer
  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Drug: lapatinib ditosylate
    Given PO
    Other Names:
    • GSK572016
    • GW-572016
    • GW2016
    • Lapatinib
    • Tykerb
  • Biological: trastuzumab
    Given IV
    Other Names:
    • anti-c-erB-2
    • Herceptin
    • MOAB HER2
  • Drug: paclitaxel
    Given IV
    Other Names:
    • Anzatax
    • Asotax
    • TAX
    • Taxol
  • Other: laboratory biomarker analysis
    Correlative studies
  • Experimental: Arm I (THL)
    Patients receive trastuzumab IV over 30-90 minutes and paclitaxel IV over 1 hour once weekly and lapatinib ditosylate PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: lapatinib ditosylate
    • Biological: trastuzumab
    • Drug: paclitaxel
    • Other: laboratory biomarker analysis
  • Active Comparator: Arm II (TH)
    Patients receive trastuzumab and paclitaxel as in arm I.
    Interventions:
    • Biological: trastuzumab
    • Drug: paclitaxel
    • Other: laboratory biomarker analysis
  • Experimental: Arm III (TL)
    Patients receive paclitaxel and lapatinib ditosylate as in arm I. (Discontinued as of 6-15-11)
    Interventions:
    • Drug: lapatinib ditosylate
    • Drug: paclitaxel
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
305
Not Provided
January 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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+ over expression by immunohistochemistry (IHC) or gene amplification by fluorescence in situ hybridization (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
  • Menopausal status not specified
  • Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1
  • Absolute neutrophil count (ANC) >= 1,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Bilirubin =< 1.5 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (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 multiple gated acquisition (MUGA) scan
  • Willing to undergo pretreatment biopsies and submit archival tissue obtained at the time of surgery
  • No concurrent pegfilgrastim
  • 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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT00770809
NCI-2009-01073, NCI-2009-01073, CALGB-40601, CDR0000616648, CALGB 40601, CALGB-40601, P30CA014236, U10CA031946
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Lisa Carey Cancer and Leukemia Group B
National Cancer Institute (NCI)
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP