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| Sponsor: | NCIC Clinical Trials Group |
|---|---|
| Collaborator: |
GlaxoSmithKline |
| Information provided by (Responsible Party): | NCIC Clinical Trials Group |
| ClinicalTrials.gov Identifier: | NCT00667251 |
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Cancer |
Biological: trastuzumab Drug: docetaxel Drug: lapatinib ditosylate Drug: paclitaxel |
Phase III |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
| Estimated Enrollment: | 600 |
| Study Start Date: | July 2008 |
| Estimated Study Completion Date: | July 2016 |
| Estimated Primary Completion Date: | June 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Lapatinib
Plus taxane based chemotherapy
|
Drug: docetaxel
75ug/u2 IV q 3 weekly, day 1 of a 3 week cycle for 8 cycles plus G-CSF
Drug: lapatinib ditosylate
1250 mg po daily
Drug: paclitaxel
80mg/m2 IV q weekly days 1, 8 and 15 of a 4-week cycle for 6 cycles.
|
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Active Comparator: Trastuzumab
Plus taxane based chemotherapy.
|
Biological: trastuzumab
IV q weekly (loading dose 4mg/kg) or IV q 3 weekly (loading dose 8mg/kg, subsequent doses 6mg/kg).
Drug: docetaxel
75ug/u2 IV q 3 weekly, day 1 of a 3 week cycle for 8 cycles plus G-CSF
Drug: paclitaxel
80mg/m2 IV q weekly days 1, 8 and 15 of a 4-week cycle for 6 cycles.
|
OBJECTIVES:
Primary
Secondary
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.
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, and then every 12 weeks thereafter (counting from the beginning of study therapy).
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically confirmed adenocarcinoma of the breast
Local or central laboratory confirmedHER2/neu* overexpressing and/or amplified disease in the invasive component of the primary or metastatic lesion as defined by the following:
PATIENT CHARACTERISTICS:
No serious cardiac illness or condition including, but not limited to, any of the following:
No serious illness or medical condition that would not allow the patient to be managed according to the protocol including, but not limited to, any of the following:
No gastrointestinal (GI) tract disease resulting in an inability to take oral medication including, but not limited to, any of the following:
No history of allergic or hypersensitivity reactions to any study drug or their excipients or to compounds with similar chemical composition to any of the study drugs
PRIOR CONCURRENT THERAPY:
At least 2 weeks since prior radiotherapy in the adjuvant or metastatic setting
Contacts and Locations
Show 257 Study Locations| Study Chair: | Karen A. Gelmon, MD | British Columbia Cancer Agency |
More Information
| Responsible Party: | NCIC Clinical Trials Group |
| ClinicalTrials.gov Identifier: | NCT00667251 History of Changes |
| Other Study ID Numbers: | MA31, CAN-NCIC-MA31, GSK-EGF108919, EUDRACT-2007-004568-27, CDR0000594764 |
| Study First Received: | April 25, 2008 |
| Last Updated: | December 5, 2011 |
| Health Authority: | United States: Food and Drug Administration; Canada: Health Canada |
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stage IV breast cancer recurrent breast cancer HER2-positive breast cancer |
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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Paclitaxel Docetaxel 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 |