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)
18 Years
N/A
Female
Breast Cancer
Trial Information
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)
The Study Drugs:
Lapatinib is designed to prevent or slow down the growth of cancer cells by blocking
proteins inside the cancer cell, called the Her2/neu receptor and the epidermal growth
factor (EGFR).
Cyclophosphamide, paclitaxel, and 5-fluorouracil are designed to block cancer cells from
dividing, which may slow or stop their growth and their ability to spread throughout the
body. This may cause the cancer cells to die.
Epirubicin is designed to attach to DNA (the genetic material of cells) which may slow or
stop their growth and cause them to die.
Study Drug Administration:
On Weeks 1-24 you will take lapatinib every day by mouth with water (about 8 ounces). It
should be taken at least 1 hour before or at least 2 hours after eating. It is important
that you take the study drug at about the same time every day. You should not eat pamelo
fruit, grapefruit, star fruit, pawpaw, and/or drink their juices while on study.
If you forget to take a dose of the study drug, you should take the missed dose as soon as
you remember, unless it has been more than 12 hours. If it has been more than 12 hours, do
not take the missed dose. Instead, take the next dose as scheduled the next day. If you
vomit after taking the study drug, wait until the next day to take your next dose.
The study drug should be stored at room temperature and out of direct sunlight. The study
drug should be kept away from children. About every 3 weeks, you will need to bring back
your empty or partially used bottle of study drug as instructed by your doctor.
On Weeks 3-12, you will receive paclitaxel through a needle in your vein 1 time a week. The
infusion will take about 1 hour. You will continue to take lapatinib every day.
On Weeks 13-24, you will receive 5-fluorouracil, epirubicin, and cyclophosphamide 1 time
every 21 day study cycle. You will receive 4 cycles. Each 5-fluorouracil infusion will
take about 3-5 minutes, each epirubicin infusion will take about 5-10 minutes, and the
cyclophosphamide infusion will take about 45-60 minutes. You will continue to take
lapatinib every day during Weeks 13-24.
If you experience intolerable side effects, the study doctor may give you drugs to help with
this side effect or change your dose of study drug.
Study Visits:
On Day 1 of Week 1, the following tests and procedures will be performed:
- You will have a physical exam, including measurement of your vital signs and weight.
- You will be asked about any drugs that you may be taking.
- You will have a performance status evaluation.
Every 3 weeks while taking combination chemotherapy and study drug, the following tests and
procedures will be performed:
- You will have a physical exam, including measurement of your vital signs and weight.
- You will be asked about any changes in your health and any drugs that you may be
taking.
- You will have a performance status evaluation.
- Your medical history will be recorded.
- Blood (about 3 tablespoons) will be drawn for routine tests.
At Week 6, you will have a CT scan, MRI, and/or a bone scan to check the status of the
disease.
At the end of the chemotherapy treatment, the disease will be measured by physical exam,
chest CT scan and sonogram to check the status of the disease. If the disease has gotten
worse, you will be taken off study. If the disease has gotten worse, you will be taken off
study. Your doctor will discuss your next step of treatment options.
Surgery:
At the end of the chemotherapy period, if the disease has responded well to the drugs, you
will have surgery to remove the breast tumor. You will sign a separate consent form for the
surgery. Either at the end-of-treatment visit at week 24 after you are done with
chemotherapy, or before the surgery, the following tests will be performed:
- You will have a complete physical exam, including measurement of your vital signs and
weight.
- You will have a performance status evaluation.
- You will be asked about any drugs you may be taking.
- Blood (about 3 tablespoons) will be drawn for routine tests
- You will have an ECG.
- You will have a MUGA or echocardiogram to check your hearts health.
- You will have a CT scan, MRI, and/or a bone scan to check the status of the disease.
- You will have a tissue biopsy to check the status of the disease.
Length of Study:
You may continue to receive the study drugs for up to 24 weeks. You will be taken off study
early if the disease gets worse or intolerable side effects occur.
Long-Term Follow-Up:
Once you are off study, you will have follow-up visits at 3 and 6 months after surgery. At
these visits, you will have a MUGA or ECHO performed.
You will have additional visits every 4 months for Years 2 and 3, and then every 6 months
for Years 4 and 5. At these visits, blood (about 3 tablespoons) will be drawn for routine
tests.
This is an investigational study. Lapatinib is FDA approved and commercially available when
taken in combination with capecitabine for another type of breast cancer. Using Lapatinib
in inflammatory breast cancer is investigational.
5-fluorouracil, epirubicin, cyclophosphamide, and paclitaxel are all FDA approved and
commercially available for treating breast cancer. The combination of these drugs is not
currently FDA approved for the treatment of IBC. At this time, this drug combination is
only being used in research.
Up to 60 patients will take part in this study. All will be enrolled at M. D. Anderson.
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. Patients with metastasis
but are candidates for mastectomy are eligible.
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 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)
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Rate of pCR after completion of all protocol specified therapy (Four cycles of lapatinib and paclitaxel followed by 4 cycles of lapatinib plus FEC75)
Outcome Time Frame:
At time of surgery following completion neoadjuvant chemotherapy (approximately 26 weeks)
Safety Issue:
Yes
Principal Investigator
Ricardo Alvarez, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
2007-0818
NCT ID:
NCT00756470
Start Date:
October 2008
Completion Date:
Related Keywords:
- Breast Cancer
- Breast Cancer
- Inflammatory Breast Cancer
- IBC
- ErbB2 overexpression
- Lapatinib
- Paclitaxel
- 5-Fluorouracil
- Epirubicin
- Cyclophosphamide
- Neoadjuvant Chemotherapy
- Breast Neoplasms
- Inflammatory Breast Neoplasms
Name | Location |
|---|---|
| UT MD Anderson Cancer Center | Houston, Texas 77030 |
