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Study Summary
No. 2007-0818:.......Breast......Ricardo Alvarez......Breast Medical Oncology
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Study Summary Title
Study Summary
Number:
2007-0818
Study Title:A Phase II Study of Neoadjuvant Lapatinib plus Chemotherapy (Sequential FEC75 and Paclitaxel) in Women with Inflammatory Breast Cancer whose Tumors Overexpress ErbB2 (Her2/neu)
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Physician New Patient Referral
Name:Ricardo AlvarezPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Breast Medical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2817
Contact us about clinical trials
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General Information
Disease Group:BreastSupported By:GlaxoSmithKline
Phase of Study:Phase IIReturn
Visit:
After pre-dose run-in phase, once every 3 weeks
Treatment
Agents:
5-Fluorouracil
Cyclophosphamide
Epirubicin
Lapatinib
Paclitaxel
Home Care:N/A
Treatment Loc:Only at MDACC
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to learn how well lapatinib taken
alone, followed by taking lapatinib with paclitaxel, and then taking lapatinib
with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC75) works to help to
control IBC. The safety of this drug combination will also be studied.
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Study Objectives / Outcomes
Primary:

The primary objective of the study is to determine the rate of pCR after completion of all protocol specified therapy. This includes the following:
  • Four cycles of lapatinib and paclitaxel followed by 4 cycles of lapatinib plus FEC75.

Secondary:

Efficacy

The secondary efficacy objectives of the study are:
  • To determine the rate of cCR after completion of all protocol specified therapy.
This includes the following:
Four cycles of lapatinib and paclitaxel followed by 4 cycles of lapatinib and FEC75

Safety

The secondary safety objectives of the study are:
  • To evaluate the cardiac safety of both the lapatinib-based treatments
  • To determine the overall safety of the lapatinib-based treatment

Biomarker Research

The biomarker research objectives of the study are:
  • To define biomarkers that would provide indication of biological effects of lapatinib on cancer cells, including putative stem cells and to examine any correlation of these with response.
  • To identify tumor tissue biomarkers present at baseline that could be predictive of cCR or benefit of lapatinib.
  • To evaluate more sensitive imaging modalities for assessment of clinical response in patients with HER-2 amplified IBC treated with lapatinib combinations.
  • To define serum biomarkers that are associated with the diagnosis of IBC and with the use of lapatinib can help examining any correlation with response.
  • To evaluate circulating tumor cells (CTCs) as other biomarker of response and benefit.
  • To define serum biomarkers that are associated with IBC and define changes during use of lapatinib and to exam any correlation of these with response


Pharmacogenetic Research

The pharmacogenetic (PGx) research objective of the study is:
  • To investigate the relationship between genetic variations in select candidate genes in the host and response (safety, efficacy, and tolerability) following treatment with lapatinib.

    Imaging Studies
  • Patients will have initial assessment of disease with standard breast imaging (mammogram, breast MRI (MRS) and sonogram) and staging procedures (CT chest abdomen, Bone scan) and PET/CT at baseline. In addition, we will include for the first time FDG-PEM (PET mammogram) at baseline (day 1) and repeated at completion of lapatinib therapy (week 2). At week 6, patients will have also the standard breast imaging (mammogram, breast MRIS and sonogram). At the completion of treatment and prior to surgery, patients will have standard breast imaging (mammogram, breast MRIS and sonogram).
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Study Status Information
Study Activation / Registration Date:10/09/2008
IRB Review and Approval Date:04/24/2008
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Open
Projected Accrual:N/A
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Have signed informed consent form (ICF) and a Patient Authorization Form (HIPAA).

2) Histological confirmation of breast carcinoma with a clinical diagnosis of IBC based on the presence of inflammatory changes in the involved breast, including diffuse erythema and edema (peau d'orange), with or without an underlying palpable mass, involving the majority of the skin of the breast. Pathologic evidence of dermal lymphatic invasion should be noted but is not required for diagnosis.

3) Tumors that overexpress ErbB2, defined as one of the following definitions: 3+ staining by immunohistochemistry and/or a FISH ratio of more than 2.2

4) Have either measurable or clinically evaluable skin disease.

5) Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 - 1.

6) Have LVEF within the institutional range of normal as measured by either echocardiogram (ECHO) or MUGA scans. The same modality must be used consistently throughout the study.

7) Willing to under go 1 mandatory core biopsy (up to 4 passes) and 1 mandatory skin biopsy to confirm IBC diagnosis and for biologic expression profiling.Subjects with clinically palpable residual disease may undergo an optional 2nd and 3rd core needle biopsy (1 after initial 2-week Lapatinib therapy and 1 after 6 months of completing all chemotherapy, before surgery) to allow identification of presumed pathways of therapy resistance. Information may give subject options for other targeted therapies (e.g. trastuzumab) if definitive surgery confirms residual disease.

8) Are able to swallow and retain oral medication (intact pill).

9) Are able to complete all screening assessments as outlined in the protocol.

10) Have adequate organ function.

11) Are subjects aged >/= 18 years with any menopausal status: Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are postmenopausal) Child-bearing potential (i.e., women with functioning ovaries and no documented impariment of oviductal or uterine function that would cause sterility.) This category includes woment with oligomenorrhea (severe), women who are perimenopausal, and young women who have begun to menustruate. Criterion continued in #13

12) These subjects must have a negative serum pregnancy test at screening and agree to one of the following: Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; or Consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject; Criterion continued in # 13

13) Any intrauterine device (IUD) with a documented failure rate of less than 1% per year; oral contraceptives (either combined or progestogen only) where not contraindicated for this subject population or per local practice.; or barrier methods, including diaphragm or condom with a spermicide. Please note that breast cancer subjects on this trial cannot receive injectable levonorgestrel or injectable progestogen due to the potential for an adverse effect of anti-hormonal therapies on chemotherapy administered for breast cancer.

Exclusion Criteria:1) Have received any prior to chemotherapy.

2) Had prior therapy with an ErbB1 and/or ErbB2 inhibitor.

3) Are receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, and biologic therapy) while taking study medication.

4) Have Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Women with ulcerative colitis are also excluded.

5) Have a concurrent disease or condition that would make the woman inappropriate for study participation, or any serious medical disorder that would interfere with the woman's safety.

6) Have an active or uncontrolled infection.

7) Have dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.

8) Have active cardiac disease, defined as one or more of the following: history of uncontrolled of symptomatic angina, history of arrhythmias requiring medications, or clinically significant; myocardial infarction < 6 months from study entry; uncontrolled or symptomatic congestive heart failure; ejection fraction below the institutional normal limit; any other cardiac condition, which is in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient

9) Are pregnant or breastfeeding.

10) Have received concurrent treatment with an investigational agent clinical trial.

11) Use of any prohibited medications concurrently with lapatinib therapy.

12) Have used investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication.

13) Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the agents used in this study or their excipients.

14) Are receiving therapeutic anti-coagulation therapy (i.e. warfarin, heparin)

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Links
Registration Number: NCT00756470
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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