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Phase II Neoadjuvant in Inflammatory Breast Cancer
This study is currently recruiting participants.
Verified by M.D. Anderson Cancer Center, October 2008
First Received: September 19, 2008   Last Updated: October 10, 2008   History of Changes
Sponsors and Collaborators: M.D. Anderson Cancer Center
GlaxoSmithKline
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00756470
  Purpose

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

Condition Intervention Phase
Breast Cancer
Drug: Lapatinib
Drug: Paclitaxel
Drug: 5-Fluorouracil
Drug: Epirubicin
Drug: Cyclophosphamide
Phase II

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Breast Cancer Cancer
Drug Information available for: Cyclophosphamide Fluorouracil Paclitaxel Epirubicin hydrochloride Epirubicin Lapatinib Lapatinib Ditosylate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official 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)

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • 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. [ Time Frame: 2 Years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To study the safety of this drug combination. [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: October 2008
Estimated Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Four cycles of lapatinib and paclitaxel followed by 4 cycles of lapatinib plus FEC75.
Drug: Lapatinib
1500 mg taken by every day by mouth weeks 1-24.
Drug: Paclitaxel
80 mg/m^2 intravenously over 1 hour every three weeks of Weeks 3-12.
Drug: 5-Fluorouracil
500 mg/m^2 intravenously over 3-5 minutes every three weeks of Weeks 13-24.
Drug: Epirubicin
75 mg/m^2 intravenously over 5-10 minutes every three weeks of Weeks 13-24.
Drug: Cyclophosphamide
500 mg/m^2 intravenously over 45-60 minutes every three weeks of Weeks 13-24.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 (2 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 impairment of oviductal or uterine function that would cause sterility.) This category includes women with oligomenorrhea (severe), women who are perimenopausal, and young women who have begun to menstruate. 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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00756470

Contacts
Contact: Massimo Cristofanilli, MD 713-792-2817

Locations
United States, Texas
U.T. M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Massimo Cristofanilli, MD            
Sponsors and Collaborators
M.D. Anderson Cancer Center
GlaxoSmithKline
Investigators
Principal Investigator: Massimo Cristofanilli, MD U.T. M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: U.T. M.D. Anderson Cancer Center ( Massimo Cristofanilli, MD / Assoc. Professor )
Study ID Numbers: 2007-0818
Study First Received: September 19, 2008
Last Updated: October 10, 2008
ClinicalTrials.gov Identifier: NCT00756470     History of Changes
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Breast Cancer
Inflammatory Breast Cancer
IBC
ErbB2 overexpression
Lapatinib
Paclitaxel
5-Fluorouracil
Epirubicin
Cyclophosphamide
Neoadjuvant Chemotherapy

Study placed in the following topic categories:
Antimetabolites
Skin Diseases
Immunologic Factors
Breast Neoplasms
Lapatinib
Antimitotic Agents
Cyclophosphamide
Protein Kinase Inhibitors
Epirubicin
Immunosuppressive Agents
Anti-Bacterial Agents
Inflammatory Breast Cancer
Paclitaxel
Fluorouracil
Tubulin Modulators
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents
Breast Diseases

Additional relevant MeSH terms:
Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Protein Kinase Inhibitors
Neoplasms by Site
Therapeutic Uses
Alkylating Agents
Breast Diseases
Skin Diseases
Mitosis Modulators
Breast Neoplasms
Enzyme Inhibitors
Lapatinib
Antimitotic Agents
Immunosuppressive Agents
Epirubicin
Pharmacologic Actions
Neoplasms
Paclitaxel
Fluorouracil
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 07, 2009