Capecitabine (Xeloda) and Lapatinib (Tykerb) as First-line Therapy in HER2/Neu-positive Breast Cancer
Condition: Breast Cancer; Metastatic Breast Cancer; Advanced Breast Cancer; HER2/Neu-positive Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Capecitabine; Lapatinib
Intervention description: The dose of capecitabine is 1000 mg/m2/dose twice each day, orally, 12 hours apart, for 14 consecutive days, every 21 days (total daily dose = 2000 mg/m2).; The daily dose of lapatinib is 1250 mg (5 tablets of 250 mg each) to be taken at approximately the same time each day, continuously. Lapatinib is taken even during the week that capecitabine is not taken.
Intervention MeSH terms: Capecitabine; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Subjects with advanced or metastatic (spread to other parts of the body) breast cancer that
      is HER2/neu-positive will take part in this study. This type of breast cancer has a high
      amount of a protein called HER2. HER2 is part of a family of receptors found on both cancer
      and normal cells. This family of receptors is important for cell growth and is found in many
      tumor types. The purpose of this research study is to compare an approved treatment for
      breast cancer capecitabine, also called Xeloda®, to the combination of capecitabine plus an
      experimental drug, lapatinib also known as Tykerb®, for treatment of advanced or metastatic
      breast cancer that is HER2/neu-positive.Capecitabine is an approved type of chemotherapy used
      to treat certain cancers including breast cancer. Capecitabine fights cancer by interfering
      with the ability of cells to divide and tumor growth. Lapatinib (Tykerb®) is considered
      "investigational", which means the drug has not been approved by the US Food and Drug
      Administration (FDA) for sale as a prescription or over-the-counter medication. Lapatinib may
      slow or stop cancer cells from growing by inhibiting the growth of cancer cells. However,
      this theory has not been proven. The addition of the study drug (lapatinib) to capecitabine
      may help stop cancer cells as well as or better than capecitabine alone. Other studies have
      demonstrated activity and tolerability of lapatinib either alone or in combination with
      capecitabine in the treatment of breast cancer.Subjects will receive capecitabine and
      lapatinib. A treatment period will be 21 days long. This period is known as a "cycle". All
      medications will be given by mouth. Subjects will take capecitabine for 2 weeks straight (Day
      1-14) followed by a 1 week without capecitabine (Day 15-21). Doses of lapatinib will be taken
      daily continuously for 21 days (Day 1-Day 21) which means that subjects will still take
      lapatinib on the week that they do not take capecitabine (Day 15-21). Subjects will continue
      to receive these medications unless they experience severe, serious and/or excessive side
      effects, the cancer becomes worse, the subjects wishes to no longer participate or the study
      doctor feels it is not in the best interest to continue treatment.Tests and procedures such
      as physical exam, blood tests, CT or MRI, ECG, ECHO and/or MUGA tests will be conducted at
      one or more of the following time points: before the study starts, before each cycle, every 6
      and 12 weeks, and after the last dose of capecitabine/lapatinib treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed invasive breast cancer

          -  Stage IIIB, IIIC with T4 lesion or Stage IV disease

          -  Breast cancer must be determined to be HER2-positive. Assays using fluorescence in
             situ hybridization (FISH) require gene amplification and assays using
             immunohistochemistry require a strongly positive (3+) staining intensity score in
             primary or metastatic tumor tissue

          -  Measurable disease according to RECIST (Response Evaluation Criteria In Solid Tumors)

          -  Age ³ 18 years of age

          -  ECOG performance status 0, 1 or 2 (Appendix B)

          -  Life expectancy of 3 months or longer

          -  Able to swallow oral medication

          -  Adequate end organ function

          -  Left ventricular ejection fraction

          -  Women of childbearing potential and men must agree to use adequate contraception prior
             to study entry and for the duration of study participation

          -  Written informed consent

        Exclusion Criteria:

          -  Prior treatment with chemotherapy for advanced or metastatic breast cancer

          -  Prior anti-ErbB1 and/or ErbB2 inhibitor therapy for breast cancer; neoadjuvant or
             adjuvant treatment with trastuzumab will be allowed provided the last dose was > 6
             months prior to enrollment in study

          -  Symptomatic or untreated brain metastases or carcinomatous meningitis

          -  Uncontrolled illnesses including symptomatic congestive heart failure, unstable angina
             pectoris, cardiac arrhythmia requiring therapy, myocardial infarction within the past
             6 months, or active infection

          -  History of other primary malignancies in the last 5 years prior to on-study date
             except carcinoma in situ of the cervix and nonmelanoma skin cancer

          -  History of allergic reaction attributed to compounds of similar chemical or biologic
             composition to capecitabine and/or lapatinib

          -  Concurrent treatment with other investigational or commercial anti-cancer agent(s)

          -  Known dihydropyrimidine dehydrogenase (DPD) deficiency

          -  Less than 3 weeks since prior radiotherapy

          -  Less than 2 weeks since prior hormonal therapy

          -  Known HIV-positive patients receiving combination anti-retroviral therapy are excluded
             from the study because of possible pharmacokinetic interactions with lapatinib

          -  Pregnant or lactating women at anytime during the study

          -  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)

          -  Certain medications that act through the CYP450 system are specifically prohibited in
             patients receiving lapatinib because in vitro data indicate that the agents has the
             potential to interact with cytochrome P450 enzymes CYP3A4. Certain other agents should
             be used with caution. Medications that are specifically prohibited can be found in
             Appendix C.