RANDOMIZED PHASE III TRIAL OF PACLITAXEL + TRASTUZUMAB + LAPATINIB VERSUS PACLITAXEL + TRASTUZUMAB AS NEOADJUVANT TREATMENT OF HER2-POSITIVE PRIMARY BREAST CANCER
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).
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
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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Pathologic complete response (pCR)
At time of surgery
Cancer and Leukemia Group B
United States: Food and Drug Administration
|Cancer and Leukemia Group B||Chicago, Illinois 60606|