Overview

This trial is active, not recruiting.

Conditions her2/neu positive, male breast carcinoma, stage iia breast cancer, stage iib breast cancer, stage iiia breast cancer, stage iiib breast cancer, stage iiic breast cancer
Treatments lapatinib ditosylate, trastuzumab, paclitaxel, laboratory biomarker analysis
Phase phase 3
Target HER2
Sponsor National Cancer Institute (NCI)
Start date December 2008
End date January 2014
Trial size 305 participants
Trial identifier NCT00770809, CALGB 40601, CALGB-40601, CDR0000616648, NCI-2009-01073, U10CA031946, U10CA180821

Summary

This randomized phase III trial studies paclitaxel and trastuzumab with or without lapatinib to see how well they work 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, by stopping them from dividing, or by stopping them from spreading. 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 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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 750 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity.
lapatinib ditosylate GSK572016
Given PO
trastuzumab ABP 980
Given IV
paclitaxel Anzatax
Given IV
laboratory biomarker analysis
Correlative studies
(Active Comparator)
Patients receive trastuzumab 2 mg/kg IV over 30-90 minutes and paclitaxel 80 mg/m^2 IV over 1 hour once weekly for 16 weeks in the absence of disease progression or unacceptable toxicity.
trastuzumab ABP 980
Given IV
paclitaxel Anzatax
Given IV
laboratory biomarker analysis
Correlative studies
(Experimental)
Patients receive paclitaxel 80 mg/m^2 IV over 1 hour once weekly and lapatinib ditosylate 15000 mg PO once daily for 16 weeks in the absence of disease progression or unacceptable toxicity. (Discontinued as of 6-15-11)
lapatinib ditosylate GSK572016
Given PO
paclitaxel Anzatax
Given IV

Primary Outcomes

Measure
pCR Rate
time frame: At time of surgery

Secondary Outcomes

Measure
Pathologic Stage in the Breast and Axilla
time frame: At time of surgery
Radiographic Response Rate (at Completion of Neoadjuvant Therapy)
time frame: Week 16
Overall Survival
time frame: Time from randomization to death or last follow-up (up to 10 years)
Relapse-free Survival (RFS)
time frame: Time from surgery to any recurrence (up to 10 years)
Time to First Failure
time frame: Time from study entry to any recurrence ( up to 10 years)
Incidence of Adverse Events as Graded by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3
time frame: Up to 30 days post-treatment

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Pathologic confirmation of invasive breast cancer; patients with inflammatory breast cancer are not eligible - Clinical stage II-III operable invasive breast cancer with intent to perform surgical resection after neoadjuvant therapy - Patients with multicentric or bilateral disease are eligible as long as the target lesion meets the eligibility criteria for this study - Staging to rule out metastatic disease is recommended for clinical stage III patients - Tumors must be HER2 positive defined as HER2 3+ by immunohistochemical (IHC) assays or gene amplification by fluorescence in situ hybridization (FISH) with a ratio of >= 2 on invasive tumor - Estrogen receptor (ER) and progesterone receptor (PgR) status must be known - The target lesion in the breast must be >= 1 cm on physical examination or by radiographic measurement; palpable axillary adenopathy will be documented but not serve as measurable disease for the primary endpoint; patients with axillary disease only are not eligible to participate - Patient agrees to provide pretreatment biopsies - No prior chemotherapy, hormone therapy, biologic, or radiation therapy with therapeutic intent for this cancer - Cardiac ejection fraction must be >= 50% by echocardiogram or multiple gated acquisition (MUGA) scan - Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status 0-1 - Patients must not be pregnant or nursing - Absolute neutrophil count (ANC) >= 1,000/ul - Platelet count >= 100,000/ul - Bilirubin =< 1.5 times upper limit of normal - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 times upper limit of normal (ULN) - Serum beta-human chorionic gonadotropin (HCG) negative (in female patients unless status-post (s/p) hysterectomy or menopausal or no menses for 24 consecutive months); assay must have a sensitivity of at least 50 mIU/mL

Additional Information

Official title Randomized Phase III Trial of Paclitaxel +Trastuzumab + Lapatinib Versus Paclitaxel + Trastuzumab as Neoadjuvant Treatment of HER2-Positive Primary Breast Cancer
Principal investigator Lisa Carey
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 American Joint Committee on Cancer (AJCC) Tumor, Lymph Nodes and Metastasis (TMN) criteria (version 6), to neoadjuvant weekly paclitaxel plus human epidermal growth factor 2 (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. 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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).