Chemotherapy and Lapatinib or Trastuzumab in Treating Women With HER2/Neu-Positive Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title: A Randomized, Open-Label, Phase III Study of Taxane Based Chemotherapy With Lapatinib or Trastuzumab as First-Line Therapy for Women With HER2/Neu Positive Metastatic Breast Cancer

Status Completed

Clinical Trial Summary

RATIONALE: HER2/neu is a receptor (protein) which is found in unusually high amounts in approximately 1 in 5 cancer patients. Scientific evidence suggests that having high amounts of the HER2/neu receptor is important for breast cancer to grow and spread. Women with previously untreated metastatic breast cancer (breast cancer that has spread to other organs) and with high levels of the HER2/neu receptor receive as their usual treatment chemotherapy with one of the approved chemotherapy drugs paclitaxel or docetaxel (called "taxanes") together with another approved drug called "trastuzumab". Chemotherapy drugs, such as paclitaxel and docetaxel, work either by killing tumour cells or by stopping them from dividing. Trastuzumab is an antibody that is given through a vein in the arm and it works by specifically "targeting" the HER2/neu i.e. it attaches to it and "turns it off". Although some of the patients who receive this taxane plus trastuzumab treatment feel better for some months, the cancer usually starts to grow again. Lapatinib is a new drug. Like trastuzumab, it also works by specifically "targeting" the HER2/neu receptor, but it does so in a different way. Lapatinib is not an antibody. It is a pill that is taken daily by mouth. Because lapatinib works in a different way than trastuzumab, it may be worse, as good as or better than trastuzumab in keeping metastatic HER/neu positive cancer from growing. However, this is not known.

Purpose: This randomized Phase III trial is comparing chemotherapy (a taxane) given together with lapatinib with chemotherapy (a taxane) given together with trastuzumab in women with HER2/neu positive breast cancer.

Clinical Trial Description

OBJECTIVES:

Primary

• To compare the progression-free survival of women with HER2/neu-positive metastatic breast cancer treated with taxane-based chemotherapy in combination with lapatinib ditosylate or trastuzumab (Herceptin®).

Secondary

• To compare the overall survival.

• To compare the time to CNS metastases at the time of first progression.

• To compare the incidence rates of CNS metastases at the time of progression.

• To compare the overall objective response rate (complete or partial response), time to response, and duration of response in patients with measurable disease at baseline.

• To compare the clinical benefit response rate.

• To compare the adverse event profile.

• To compare the quality of life.

• To compare clinical outcomes using biomarker changes in biological samples.

• To compare health economics, including healthcare utilization and health utilities.

OUTLINE: This is a multicenter study. Patients are stratified according to prior neoadjuvant/adjuvant anti-HER2/neu-targeted therapy (yes vs no), prior neoadjuvant/adjuvant taxane chemotherapy (yes vs no), planned taxane therapy (paclitaxel vs docetaxel), and liver metastasis (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive either paclitaxel IV on days 1, 8, and 15; treatment with paclitaxel repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Alternatively, patients may receive docetaxel IV on day 1; treatment with docetaxel repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients on docetaxel also receive filgrastim (G-CSF) according to institutional standard. All patients receive oral lapatinib ditosylate once daily during taxane treatment and continue after completion of taxane treatment, in the absence of disease progression or unacceptable toxicity.

• Arm II: Patients receive paclitaxel IV on days 1, 8, and 15 and trastuzumab (Herceptin®) IV on days 1, 8, 15, and 22. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Alternatively, patients may receive docetaxel IV and trastuzumab IV on day 1. Treatment repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. After completion of taxane chemotherapy and trastuzumab, all patients receive trastuzumab alone IV once every 3 weeks in the absence of disease progression or unacceptable toxicity.

Formalin-fixed paraffin-embedded tissue samples are analyzed for ER, PgR, EGFR, CK5/6, Ki67, and other molecular biomarkers by tissue microarray and immunohistochemistry.

Patients complete quality of life questionnaires (EORTC QLQ-C30 and a Trial Specific Checklist) at baseline, every 12 weeks for 96 weeks, and then every 24 weeks until disease progression.

After completion of study treatment, patients are followed at 4 weeks post treatment, and then every 12 weeks thereafter (counting from the beginning of study therapy). ;

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

• NCT number: NCT00667251
• Study type: Interventional
• Source: Novartis
• Status: Completed
• Phase: Phase 3
• Start date: October 7, 2008
• Completion date: July 27, 2022