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
  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. 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.


Condition Intervention Phase
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
Biological: trastuzumab
Drug: paclitaxel
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: RANDOMIZED PHASE III TRIAL OF PACLITAXEL + TRASTUZUMAB + LAPATINIB VERSUS PACLITAXEL + TRASTUZUMAB AS NEOADJUVANT TREATMENT OF HER2-POSITIVE PRIMARY BREAST CANCER

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Pathologic complete response (pCR) [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 305
Study Start Date: December 2008
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
Active Comparator: Arm II (TH)
Patients receive trastuzumab and paclitaxel as in arm I.
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 III (TL)
Patients receive paclitaxel and lapatinib ditosylate as in arm I. (Discontinued as of 6-15-11)
Drug: lapatinib ditosylate
Given PO
Other Names:
  • GSK572016
  • GW-572016
  • GW2016
  • Lapatinib
  • Tykerb
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol

Detailed Description:

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.

  Eligibility

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

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
  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: NCT00770809

  Show 300 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Lisa Carey Cancer and Leukemia Group B
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00770809     History of Changes
Other Study ID Numbers: NCI-2009-01073, NCI-2009-01073, CALGB-40601, CDR0000616648, CALGB 40601, CALGB-40601, P30CA014236, U10CA031946
Study First Received: October 9, 2008
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Lapatinib
Paclitaxel
Trastuzumab
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 20, 2014