Study In Women And Men With Metastatic Breast Cancer That Have Overexpression Of ErbB2
Condition: Neoplasms, Breast
MeSH terms: Breast Neoplasms
Intervention: Lapatinib (GW572016) oral tablets; Paclitaxel infusion; Placebo
Intervention description: 1500 mg oral daily continuously; Paclitaxel 80 mg/m2 every 3 weeks, 4th week rest for minimum 6 months; Paclitaxel Matching Placebo
Intervention MeSH terms: Paclitaxel; Lapatinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 444.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: ErbB2 positive; human epidermal growth factor receptor 2 positive (Her2+); metastatic breast cancer; Fluorescence in situ hybridization (FISH) positive; Stage IV

Summary:

      This was a randomized, double-blind, placebo-controlled, multicenter, Phase III study to
      evaluate and compare the efficacy and safety of Lapatinib + Paclitaxel versus Placebo +
      Paclitaxel in men and women with ErbB2 amplified metastatic (Stage IV) breast cancer who had
      not received prior therapy for metastatic disease.
    

Eligibility criteria:

        Inclusion criteria:

          -  Signed informed consent;

          -  Male or female ≥18 years;

          -  Histologically confirmed invasive breast cancer with stage IV disease; If the disease
             is restricted to a solitary lesion, its neoplastic nature should be confirmed by
             cytology or histology.

          -  Documented amplification of ErbB2 by fluorescence in situ hybridization (FISH) in
             primary or metastatic tumor tissue by the central laboratory for randomization into
             the study;

          -  If a taxane was administered in the neoadjuvant or adjuvant setting, progression must
             have occurred >12 months after completion of this treatment and the patient recovered
             from all associated toxicities;

          -  Measurable lesion(s) according to RECIST (Response Evaluation Criteria in Solid
             Tumors);

          -  Radiotherapy as palliative treatment for painful metastatic disease is permitted but
             must have been stopped within 2 weeks prior to initiation of any investigational
             treatment. All subjects must have recovered from all radiotherapy related toxicities
             prior to initiation of any investigational treatment. The site of radiotherapy must
             not be used as a site of measurable disease;

          -  Bisphosphonate therapy for bone metastases and is allowed; however, treatment must be
             initiated prior to the first dose of investigational treatment. Prophylactic use of
             bisphosphonates in subjects without bone disease is not permitted, except for the
             treatment of osteoporosis;

          -  For those patients whose disease is ER+ and/or PR+ the following criteria should be
             met:

        Patients with visceral disease that requires chemotherapy (eg., patients with liver or lung
        metastases) Rapidly progressing or life threatening disease, as determined by the
        investigator Patients who received hormonal therapy and are no longer benefiting from this
        therapy and the hormonal treatment must have been stopped before the first dose of
        investigational treatment;

          -  Cardiac ejection fraction within institutional range of normal as measured by
             echocardiogram. MUGA scans will be accepted in cases where an echocardiogram cannot be
             performed or is inconclusive;

          -  ECOG Performance Status of 0 to 1;

          -  Life expectancy of ≥ 12 weeks;

          -  Able to swallow and retain oral medication;

          -  Archived tumor tissue available for testing;

          -  Women and men with potential to have children must be willing to practice acceptable
             methods of birth control during the study;

          -  Willing to complete all screening assessments as outlined in the protocol;

          -  Adequate organ function as defined in Table 1 Baseline Laboratory Values;

        Exclusion Criteria:

          -  Pregnant or lactating females at anytime during the study

          -  Subjects with only non-measurable metastatic sites of disease per RECIST, (e.g. bone
             metastases, pleural effusion, or ascites, etc. (Refer to Section 5.3 Efficacy for list
             sites considered to be non-measurable disease.);

          -  Received prior chemotherapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2
             therapy for metastatic disease.

          -  Prior therapy with an ErbB1 and/or ErbB2 inhibitor, other than trastuzumab in the
             adjuvant setting. If trastuzumab was administered in the adjuvant setting, then > 12
             months must have elapsed since completion of trastuzumab therapy;

          -  Planned concurrent anti-cancer therapy (chemotherapy, radiation therapy,
             immunotherapy, biologic therapy, hormonal therapy) while taking investigational
             treatment;

          -  Unresolved or unstable, serious toxicity from prior administration of another
             investigational drug and/or of prior cancer treatment;

          -  Peripheral neuropathy of Grade 2 or greater;

          -  Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
             resection of the stomach or small bowel. Subjects with ulcerative colitis are also
             excluded;

          -  History of other malignancy. However, subjects who have been disease-free for 5 years,
             or subjects with a history of completely resected non-melanoma skin cancer or
             successfully treated in situ carcinoma, are eligible;

          -  Concurrent disease or condition that would make the subject inappropriate for study
             participation, or any serious medical disorder that would interfere with the subject's
             safety;

          -  Uncontrolled infection;

          -  Dementia, altered mental status, or any psychiatric condition that would prohibit the
             understanding or rendering of informed consent;

          -  Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart
             failure;

          -  Known history or clinical evidence of central nervous system (CNS) metastases or
             leptomeningeal carcinomatosis;

          -  Concurrent treatment with prohibited medications, including herbal remedies and
             Chinese traditional medicines;

          -  Concurrent treatment with an investigational agent or participation in another
             clinical trial involving investigational agents;

          -  Used an investigational drug within 30 days or 5 half-lives, whichever is longer,
             preceding the first dose of investigational treatment;

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to paclitaxel or lapatinib or their excipients.