Last updated: 11/03/2018 10:10:21
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.
Chemotherapy and Lapatinib or Trastuzumab in Treating Women With HER2/neu-Positive Metastatic Breast Cancer
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Progression-free survival
Timeframe: From randomization to RECIST V 1.0 progression or death assessed up to 39 months.
Secondary outcomes:
Effects of changes in biomarkers on clinical outcomes
Timeframe: Not available at this time
Clinical benefit response rate (HER2/neu+))
Timeframe: 24 weeks
Overall Objective Response Rate (complete or partial) HER2/neu+
Timeframe: Median follow-up of 21.5 months.
Time to CNS metastases at the time of first progression
Timeframe: From randomization to CNS metastases at time of first progression, assessed up to 39 months.
CNS metastases at the time of progression (HER2+)
Timeframe: Incidence rate of CNS mestastes at first progression, assessed up to 39 months
CNS metastases at the time of progression (ITT)
Timeframe: Incidence rate of CNS metastases at first progression assessed up to 39 months
Economic evaluation, including health utilities, as measured by the EQ-5D questionnaire, and healthcare utilization
Timeframe: Not available at this time
Quality of life as measured by the EORTC QLQ-C30 Global Score from Baseline to 12 weeks
Timeframe: 12 weeks
Clinical benefit response rate (ITT)
Timeframe: 24 weeks
Overall objective response rate (complete or partial) ITT
Timeframe: 4 years
Overall Survival
Timeframe: From randomization to death from any cause, assessed up to 44 months.
Interventions:
Enrollment:
652
Primary completion date:
2012-01-08
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Breast Cancer
Product
lapatinib
Collaborators
NCIC-Clinical Trials Group
Study date(s)
October 2008 to December 2016
Type
Interventional
Phase
3
Participation criteria
Sex
Female
Age
18+ years
Accepts healthy volunteers
none
- DISEASE CHARACTERISTICS:
- * Histologically confirmed adenocarcinoma of the breast
Inclusion and exclusion criteria
Inclusion criteria:
- DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the breast * Metastatic (stage IV) disease at primary diagnosis or at relapse after curative intent therapy * 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:
- 3+ overexpression (in > 30% of invasive tumor cells) by immunohistochemistry (IHC)
- 2+ or 3+ overexpression (in ≤ 30% of invasive tumor cells) by IHC AND demonstrates HER2/neu gene amplification by fluorescence in situ hybridization (FISH) or chromogenic in situ hybridization (CISH)
- HER2/neu gene amplification by FISH/CISH (> 6 HER2/neu gene copies per nucleus, or a FISH/CISH ratio [HER2 gene copies to chromosome 17 signals] of ≥ 2.2) NOTE: *Patients with a negative or equivocal overall result (FISH/CISH ratio of < 2.2, ≤ 6.0 HER2/neu gene copies per nucleus, or staining scores of 0, 1+, 2+, or 3+ [in ≤ 30% of neoplastic cells] by IHC) are not eligible * Formalin-fixed paraffin-embedded tumor specimen available * No CNS metastases (including leptomeningeal involvement) * Hormone receptor status not specified 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 or lobular 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
- 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: * Recovered from all prior therapy * No prior chemotherapy, immunotherapy, biological therapy, or anti-HER2/neu-targeted therapy for recurrent or metastatic breast cancer * At least 12 months since prior chemotherapeutic agents, including taxanes, in the neoadjuvant or adjuvant setting * At least 12 months since prior anti-HER2/neu-targeted therapy in the neoadjuvant or adjuvant setting * Prior treatment with endocrine therapy in the neoadjuvant, adjuvant, or metastatic setting allowed * At least 2 weeks since prior radiotherapy in the adjuvant or metastatic setting
- Prior radiotherapy to a solitary metastatic lesion allowed provided there is documented disease progression after completion of radiotherapy * More than 30 days (or 5 half-lives) since prior investigational drugs * At least 7 days since prior and no concurrent CYP3A4 inhibitors (6 months for amiodarone) * At least 14 days since prior and no concurrent CYP3A4 inducers * No prior surgical procedures affecting absorption (e.g., resection of stomach or small bowel) * No concurrent palliative radiotherapy * No other concurrent anticancer treatment * No other concurrent investigational drugs for breast cancer
Trial location(s)
This study does not involve prospective enrollment of participants.
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
No longer a GSK study
Actual primary completion date
2012-01-08
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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