Ellie (Alice) Guardino
Phase II Neoadjuvant Doxorubicin and Cyclophosphamide -> Docetaxel with Lapatinib in Stage II/III Her2Neu+ Breast Cancer
Contact Information
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Brief
This trial combines dose dense chemotherapy with Doxorubicin and Cyclophosphamide (AC) followed by standard every 3 week docetaxel and GW572016 for neoadjuvant treatment of her2neu positive stage II/III breast cancer. GW572016 or Lapatinib, the investigational agent, acts as a duel inhibitor of both epidermal growth factor receptor (EGFR) and ErbB-2 (Her2/neu) tyrosine kinase activity. EGFR and ErbB2 receptors are frequently over-expressed or altered in human cancers including breast cancer. This study plans to determine the antitumor activity of this regimen and its effectiveness of preventing tumor growth and spread.
Recruiting Status:
RecruitingStanford Recruiting Status:
RecruitingCondition(s):
Intervention(s):
- Drug: Lapatinib
- Drug: Doxorubicin
- Drug: Cyclophosphamide
- Drug: Docetaxel
Phase:
Phase 2Eligibility
Ages Eligible for Study:
18 years to 70 yearsGenders Eligible for Study:
FemaleHealth of Volunteers:
People with the conditions listed in this trial can participate as controls.Key Inclusion Criteria:
- Women with histologically confirmed Her2neu positive breast cancer. Patients are considered Her2Neu positive 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 bidimensional, measurable indicator lesion. All sites of disease should be noted and followed. Baseline measurements and evaluations of tumor must be done within 3 weeks prior to initiation of treatment.
- Patients must be between 18 and 70 years of age
- 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 MUGA scan. Note that baseline and on treatment scans should be performed using the same modality and preferably at the same institutions
- Patients must have normal organ and marrow function as defined below:
o Hematologic (minimal values)
a. Absolute neutrophil count > 1,500/mm3
b. Hemoglobin > 8.0 g/dl
c. Platelet count > 100,000/mm^3
o Creatinine within normal institutional limits
o Hepatic
a. Total Bilirubin equal to or less than ULN
b. AST and ALT and Alkaline Phosphatase must be within the range allowing for eligibility.
c. 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
o Antacid use is prohibited 1 hour before and 1 hour after GW572016 dosing.
o All herbal (alternative) medicines are prohibited. In addition please see section 6.6 of the protocol regarding medications that are prohibited during the administration of GW572016 and for the duration of GW572016.
- The effects of GW572016 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential and men 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. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Must have negative pregnancy test if of child bearing years.
- Peripheral neuropathy: must be < grade 1
- Able to swallow and retain oral medication
Key Exclusion Criteria:
- Evidence of disease outside the breast or chest wall, except for ipsilateral axillary , supraclavicular, or infraclavicular lymph nodes.
- 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 five years, 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. Patients 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 patients whose circumstances do not permit completion of the study or the required follow-up.
- Patients who have congestive heart failure, abnormal 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 females, or females of childbearing potential not employing adequate contraception.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW572016.
- HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with GW572016. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.
- Patients with 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).
- Patients with a history of severe hypersensitivity reaction to Taxotere? or other drugs formulated with polysorbate 80.
Additional Study Details
Official Title:
Phase II Neoadjuvant Chemotherapy Trial in Clinical Stage II/III Her2Neu Positive Breast Cancer with Sequential AC -> Docetaxel with Concurrent Dual EGFR Kinase Blockade by GW572016 (Lapatinib) followed by 1 Year Adjuvant TrastuzumabAnticipated start date:
10/26/2006Lead Sponsor:
Stanford UniversityCollaborator(s):
- GlaxoSmithKline
- Sanofi-Aventis
Investigator(s):
Study Type:
InterventionalPurpose:
TreatmentAllocation:
Non-randomizedMasking:
OpenControl:
noneAssignment:
Single GroupEndpoints:
UnspecifiedPrimary Outcomes:
- Pathologic complete response
Secondary Outcomes:
- Radiological complete response
- Rate of breast conserving surgery
- Side effects and toxicity profile of Docetaxel and GW572016 (Lapatinib)
- Disease free survival
Total Number to be Enrolled:
71Total Number to be Enrolled at Stanford:
71More Information
Secondary ID(s):
- 96692
- BRSADJ0002
- NCT00404066
Locations & Contacts
Stanford Locations & Contacts:
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Non-Stanford Locations:
The Stanford website does not have any locations outside of Stanford listed for this trial. You may want to check clinicaltrials.gov for posible additional locations.
This listing was last updated:
9/15/2009PLEASE NOTE:
Study Coordinators and Research Nurses cannot give medical advice over the phone. Telephone numbers are provided for obtaining additional information on specific clinical research trials only. If you have specific questions which require clinical expertise, please call your primary care physician. If you do not have a primary care physician please feel free to call the SHC Physician Referral Service at (800) 756-9000 or send an email.
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