Phase 2 Neoadjuvant Doxorubicin and Cyclophosphamide -> Docetaxel With Lapatinib in Stage II/III Her2Neu+ Breast Cancer
NCT ID: NCT00404066
Last Updated: 2017-12-22
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
21 participants
INTERVENTIONAL
2006-10-31
2011-03-31
Brief Summary
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Detailed Description
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Neoadjuvant chemotherapy which achieves pathologic complete responses (pCR) has been shown to predict improved long-term survival and serves as a surrogate for clinical outcome. By using this primary endpoint we can obtain statistical data with smaller patient numbers and at a lower overall cost. Additionally, we hope to correlate clinical and radiologic outcomes with gene expression data.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Neoadjuvant Chemotherapy
Doxorubicin (Adriamycin) + cyclophosphamide (Cytoxan) with pegfilgrastim or filgrastim growth factor support every 2 weeks for 4 cycles, followed by docetaxel + lapatinib for four 21-day cycles, followed by surgery. Dexamethasone was administered twice-a-day for 3 days, starting 24 hours before the docetaxel infusions. After surgery +/- radiation, participants may receive trastuzumab (Herceptin) for a year.
Lapatinib
1250 mg, tablets, oral daily during treatment with docetaxel (3-week cycles x 4 cycles)
Doxorubicin
60 mg/m2, intravenously every 2 weeks for 4 cycles. Given as first treatment with cyclophosphamide.
Cyclophosphamide
600 mg/m2, intravenously every 2 weeks for 4 cycles. Given as first treatment with doxorubicin.
Docetaxel
100 mg/m2, intravenously every 3 weeks for 4 cycles (after treatment cycles of doxorubicin and cyclophosphamide
Pegfilgrastim
6 mg, subcutaneously on day 2 of all cytotoxic chemotherapy treatments.
Filgrastim
300 or 480 mcg, subcutaneously on days 3 to 10 after cytotoxic chemotherapies.
Dexamethasone
8 mg, oral taken twice a day for 3 days starting 24 hours before docetaxel
Trastuzumab
Loading dose 8 mg/kg, then 6 mg/kg, intravenously every 3 weeks for 1 year
Interventions
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Lapatinib
1250 mg, tablets, oral daily during treatment with docetaxel (3-week cycles x 4 cycles)
Doxorubicin
60 mg/m2, intravenously every 2 weeks for 4 cycles. Given as first treatment with cyclophosphamide.
Cyclophosphamide
600 mg/m2, intravenously every 2 weeks for 4 cycles. Given as first treatment with doxorubicin.
Docetaxel
100 mg/m2, intravenously every 3 weeks for 4 cycles (after treatment cycles of doxorubicin and cyclophosphamide
Pegfilgrastim
6 mg, subcutaneously on day 2 of all cytotoxic chemotherapy treatments.
Filgrastim
300 or 480 mcg, subcutaneously on days 3 to 10 after cytotoxic chemotherapies.
Dexamethasone
8 mg, oral taken twice a day for 3 days starting 24 hours before docetaxel
Trastuzumab
Loading dose 8 mg/kg, then 6 mg/kg, intravenously every 3 weeks for 1 year
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Histologically-confirmed Her2neu positive breast cancer, by either Immunohistochemistry (IHC) 3+ or Fluorescence In Situ Hybridization (FISH)+
* Stage II/III breast cancer including any large primary tumor (\> 2 cm), tumors of any size associated with skin or chest wall involvement, tumors of any size with axillary lymph node involvement, (T2-T4, N0-N2) and those with ipsilateral subclavicular or supraclavicular lymph nodes).
* At least one bi-dimensional, measurable indicator lesion.
* Between 18 and 70 years of age
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 / Karnofsky ≥ 60% at screening and on the first day of treatment.
* Informed consent must be obtained prior to registration.
* Cardiac ejection fraction within the institutional range of normal as measured by multigated acquisition (MUGA) or echocardiography (ECHO) scan.
* Absolute neutrophil count \> 1,500/mm³
* Hemoglobin \> 8.0 g/dL
* Platelet count \> 100,000/mm³
* Creatinine within normal institutional limits
* Total Bilirubin equal to or less than institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST); alanine aminotransferase (ALT); and alkaline phosphatase must be within the range allowing for eligibility. In determining eligibility the more abnormal of the two values (AST or ALT) should be used.
* Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of GW572016 will be determined following review of their use by the Principal Investigator
* Antacid use is prohibited 1 hour before and 1 hour after GW572016 dosing.
* All herbal (alternative) medicines are prohibited.
* Medications prohibited during the administration of lapatinib .
* Women of child-bearing potential must have negative pregnancy test and must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation.
* Peripheral neuropathy: must be \< grade 1
* Able to swallow and retain oral medication
Exclusion Criteria
* Prior chemotherapy, immunotherapy, or hormonal therapy for breast cancer.
* More than 3 months between histologic diagnosis and registration on this study.
* History of other malignancy within the last 5years, except curatively treated basal cell carcinoma of the skin or carcinoma in situ of the cervix.
* Psychological, familial, sociological or geographical conditions which do not permit weekly medical follow-up and compliance with the study protocol. Those who are medically-unstable, including but not limited to active infection, acute hepatitis, deep vein thrombosis requiring anticoagulant therapy, gastrointestinal bleeding, uncontrolled hypercalcemia, uncontrolled diabetes, dementia, seizures, superior vena cava syndrome, and those whose circumstances do not permit completion of the study or the required follow-up.
* Congestive heart failure, abnormal left ventricular ejection fraction (LVEF), angina pectoris, uncontrolled cardiac arrhythmias, or other significant heart disease, or who have had a myocardial infarction within the past year.
* Pregnant or lactating
* Of childbearing potential and not employing adequate contraception
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW572016.
* HIV-positive and receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with lapatinib. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.
* GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).
* History of severe hypersensitivity reaction to taxotere or other drugs formulated with polysorbate 80.
* Current active hepatic or biliary disease (with exception of patients with Gilberts syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment ).
18 Years
70 Years
FEMALE
No
Sponsors
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GlaxoSmithKline
INDUSTRY
Sanofi
INDUSTRY
George Albert Fisher
OTHER
Responsible Party
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George Albert Fisher
Associate Professor of Medicine
Principal Investigators
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George A Fisher, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Stanford University
Locations
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Santa Clara Valley Medical Center
San Jose, California, United States
Stanford University School of Medicine
Stanford, California, United States
Countries
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Other Identifiers
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BRSADJ0002
Identifier Type: OTHER
Identifier Source: secondary_id
IRB-03518
Identifier Type: -
Identifier Source: org_study_id