Clinical trial NCT00756470
Conditions: Breast Cancer
Keywords: Breast Cancer Inflammatory Breast Cancer IBC ErbB2 overexpression Lapatinib Paclitaxel 5-Fluorouracil Epirubicin Cyclophosphamide Neoadjuvant Chemotherapy
Sponsor: M.D. Anderson Cancer Center
Start date: 2008-10-01; Completion date: 2013-10-01
Enrollment: 15 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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 Inflammatory Breast Cancer (IBC). The safety of this drug combination will also be studied.

Detailed description:
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 multiple gated acquisition scan (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.

Arms: arm 1: Four cycles of Lapatinib and Paclitaxel followed by 4 cycles of Lapatinib plus 5-Fluorouracil, Cyclophosphamide, Epirubicin (FEC75). Cycle is 21 days.

Lapatinib alone at 1,000 mg orally once daily for a 2-week run-in period, followed by initiation of chemotherapy with 2 combination regimens of 4 cycles each.

1. Week 3 Paclitaxel 80 mg/m\^2 weekly for 4 cycles (12 weeks) administered on Day 1, Day 8, and Day 15) of each cycle combined with Lapatinib 750 mg orally once daily.
2. Week 15, second combination treatment consisting of Lapatinib (1,000 mg orally once daily) combined with FEC75 (5-FU 500 mg/m\^2, Epirubicin 75 mg/m\^2, and Cyclophosphamide 500 mg/m\^2 every 3 weeks for 4 cycles).
Interventions: intervention 1: Lapatinib intervention 2: Paclitaxel intervention 3: 5-Fluorouracil (5-FU) intervention 4: Epirubicin intervention 5: Cyclophosphamide
Intervention descriptions: intervention 1: 1000 mg taken by every day by mouth (PO) weeks 1 and 2; then starting day 15 for 12 weeks (weeks 3 to 14) daily 750 mg PO. Week 15, second combination treatment consisting of lapatinib (1,000 mg orally once daily) combined with FEC7. intervention 2: 80 mg/m\^2 intravenously over 1 hour weekly for 4 cycles administered on Day 1, Day 8, and Day 15 of each cycle then weekly starting day 15 for 12 weeks. intervention 3: 500 mg/m\^2 intravenously over 3-5 minutes every three weeks of Weeks 13-24. intervention 4: 75 mg/m\^2 intravenously over 5-10 minutes every three weeks of Weeks 13-24. intervention 5: 500 mg/m\^2 intravenously over 45-60 minutes every three weeks of Weeks 13-24.

Protocol documents: