Chemotherapy and Lapatinib or Trastuzumab in Treating Women With HER2/Neu-Positive Metastatic Breast Cancer
Tracking InformationStart Date ICMJE | July 2008 |
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Estimated Primary Completion Date | July 2011 (final data collection date for primary outcome measure) |
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Current Primary Outcome Measures ICMJE (submitted: April 25, 2008) | Progression-free survival [ Designated as safety issue: No ] |
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Original Primary Outcome Measures ICMJE | Same as current |
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Change History | Complete list of historical versions of study NCT00667251 on ClinicalTrials.gov Archive Site |
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Current Secondary Outcome Measures ICMJE (submitted: April 25, 2008) | - Overall survival [ Designated as safety issue: No ]
- Time to CNS metastases at the time of first progression [ Designated as safety issue: No ]
- Incidence rates of CNS metastases at the time of progression [ Designated as safety issue: No ]
- Overall objective response rate, time to response, and duration of response [ Designated as safety issue: No ]
- Clinical benefit response rate [ Designated as safety issue: No ]
- Adverse event profile [ Designated as safety issue: Yes ]
- Quality of life as measured by the EORTC QLQ-C30 questionnaire and a Trial Specific Checklist [ Designated as safety issue: No ]
- Clinical outcomes as measured by biomarker changes in biological samples [ Designated as safety issue: No ]
- Economic evaluation, including health utilities, as measured by the EQ-5D questionnaire, and healthcare utilization [ Designated as safety issue: No ]
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Original Secondary Outcome Measures ICMJE | Same as current |
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Descriptive InformationBrief Title ICMJE | Chemotherapy and Lapatinib or Trastuzumab in Treating Women With HER2/Neu-Positive Metastatic Breast Cancer |
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Official Title ICMJE | 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 |
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Brief Summary | RATIONALE: Drugs used in chemotherapy, such as paclitaxel and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. It is not yet known whether chemotherapy is more effective with lapatinib or trastuzumab in treating patients with breast cancer. PURPOSE: This randomized phase III trial is studying chemotherapy and lapatinib to see how well they work compared with chemotherapy and trastuzumab in treating women with HER2/neu-positive metastatic breast cancer. |
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Detailed 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 OR docetaxel IV on day 1. Treatment with paclitaxel repeats every 4 weeks for 6 courses and treatment with docetaxel repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral lapatinib ditosylate once daily 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, 12 weeks, and then every 12 weeks thereafter. |
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Study Phase | Phase III |
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Study Type ICMJE | Interventional |
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Study Design ICMJE | Treatment, Randomized, Open Label |
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Condition ICMJE | Breast Cancer |
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Intervention ICMJE | - Biological: trastuzumab
Given IV - Drug: lapatinib ditosylate
Given orally
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Study Arms / Comparison Groups | - Arm I: Experimental
Patients receive either paclitaxel IV on days 1, 8, and 15 OR docetaxel IV on day 1. Treatment with paclitaxel repeats every 4 weeks for 6 courses and treatment with docetaxel repeats every 3 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients also receive oral lapatinib ditosylate once daily in the absence of disease progression or unacceptable toxicity. Intervention: Drug: lapatinib ditosylate - Arm II: Active Comparator
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. Intervention: Biological: trastuzumab
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Recruitment InformationEstimated Enrollment ICMJE | 600 |
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Completion Date | |
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Estimated Primary Completion Date | July 2011 (final data collection date for primary outcome measure) |
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Eligibility Criteria ICMJE | DISEASE CHARACTERISTICS: PATIENT CHARACTERISTICS: - Menopausal status not specified
- ECOG performance status 0-2
- Life expectancy > 6 months
- Absolute granulocyte count > 1,500/mm³
- Platelet count > 75,000/mm³
- Hemoglobin > 10 g/dL
- Serum creatinine ≤ 2.0 times upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 times ULN (< 3 times ULN for patients with Gilbert's disease)
- AST and/or ALT ≤ 2.5 times ULN (< 5 times ULN for patients planning to receive paclitaxel-based therapy)
- LVEF ≥ 50% by MUGA or ECHO
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Must be accessible for study treatment and follow-up
- No history of other malignancies, except adequately treated ductal carcinoma in situ, adequately treated nonmelanoma skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumor (non-breast) with no evidence of disease for > 5 years
No serious cardiac illness or condition including, but not limited to, any of the following: - History of documented congestive heart failure or systolic dysfunction (LVEF < 50%)
- High-risk uncontrolled arrhythmias (i.e., ventricular tachycardia, high-grade atrioventricular block, or supraventricular arrhythmias that are not adequately rate-controlled)
- Unstable angina pectoris requiring anti-anginal medication
- Clinically significant valvular heart disease
- Evidence of transmural infarction on ECG
- Inadequately controlled hypertension (i.e., systolic blood pressure [BP] > 180 mm Hg or diastolic BP > 100 mm Hg)
- New York Heart Association class III-IV functional status
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: - History of significant neurologic or psychiatric disorder that would impair the ability to obtain informed consent or limit compliance with study requirements
- Active uncontrolled infection
- Serious or nonhealing wound, ulcer, or bone fracture
- No peripheral neuropathy ≥ grade 2
No gastrointestinal (GI) tract disease resulting in an inability to take oral medication including, but not limited to, any of the following: - Malabsorption syndrome
- Requirement for IV alimentation
- Uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
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 allergic reactions to taxanes are allowed provided they were adequately treated and, according to the treating physician, would not prohibit further treatment with taxanes
PRIOR CONCURRENT THERAPY: |
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Gender | Female |
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Ages | 18 Years and older |
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Accepts Healthy Volunteers | No |
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Contacts ICMJE | |
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Location Countries ICMJE | United States, Australia, Belgium, Canada, France, Germany, Israel, Italy, Japan, Netherlands, Poland, Russian Federation, Spain, Taiwan, United Kingdom |
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Administrative InformationNCT ID ICMJE | NCT00667251 |
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Responsible Party | Joseph L. Pater, Cancer Research Institute at Queen's University |
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Study ID Numbers ICMJE | CDR0000594764, CAN-NCIC-MA31, GSK-EGF108919, EUDRACT-2007-004568-27 |
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Study Sponsor ICMJE | NCIC Clinical Trials Group |
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Collaborators ICMJE | GlaxoSmithKline |
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Investigators ICMJE | Study Chair: | Karen A. Gelmon, MD | British Columbia Cancer Agency | | Study Chair: | Karen A. Gelmon, MD | British Columbia Cancer Agency | |
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Information Provided By | National Cancer Institute (NCI) |
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