Paclitaxel and Trastuzumab With or Without Lapatinib in Treating Patients With Stage II or Stage III Breast Cancer That Can Be Removed by Surgery
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 Other: pharmacogenomic studies |
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 |
- Pathologic complete response (pCR) [ Time Frame: At time of surgery ] [ Designated as safety issue: No ]
- 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 ]
| Estimated Enrollment: | 300 |
| Study Start Date: | December 2008 |
| Estimated 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:
Biological: trastuzumab
Given IV
Other Names:
Drug: paclitaxel
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study
|
|
Active Comparator: Arm II (TH)
Patients receive trastuzumab and paclitaxel as in arm I.
|
Biological: trastuzumab
Given IV
Other Names:
Drug: paclitaxel
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study
|
|
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:
Drug: paclitaxel
Given IV
Other Names:
|
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 |
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 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, CALGB 40601, CALGB-40601, CDR0000616648, U10CA031946 |
| Study First Received: | October 9, 2008 |
| Last Updated: | March 26, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Breast Neoplasms, Male Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Paclitaxel Trastuzumab Lapatinib Tubulin Modulators |
Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents, Phytogenic Antineoplastic Agents Therapeutic Uses Protein Kinase Inhibitors Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 19, 2013