ErbB2 Over-expressing Metastatic Breast Cancer Study Using Paclitaxel, Trastuzumab, and Lapatinib
Condition: Neoplasms, Breast
MeSH terms: Breast Neoplasms
Intervention: lapatinib; paclitaxel; trastuzumab
Intervention description: (GW572016) 1000 mg QD; 80 mg/m2 IV weekly for three weeks; 4 mg/kg loading dose and 2 mg/kg weekly IV
Intervention MeSH terms: Paclitaxel; Trastuzumab; Lapatinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 63.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: trastuzumab; ErbB2; paclitaxel; Herceptin; Taxol; ErbB1; metastatic breast cancer; Stage IV breast cancer; lapatinib

Summary:

      This study was originally designed as a Phase III randomized, double blind, placebo
      controlled study to assess the safety and tolerability, and efficacy of paclitaxel plus
      trastuzumab plus lapatinib compared with paclitaxel plus trastuzumab plus placebo in women
      with ErbB2 overexpressing metastatic breast cancer. The planned study was a two stage design
      with an initial open-label safety stage to be conducted in approximately 65 subjects followed
      by a randomized phase conducted in a further 700 subjects. The open-label part of the study
      sequentially enrolled three cohorts with patients receiving a different dose combination of
      paclitaxel, trastuzumab and lapatinib. Following poor recruitment rate in the open label
      stage, the randomized stage of the study was terminated, thus no subjects were enrolled into
      the randomization stage.
    

Eligibility criteria:

        Inclusion criteria:

          -  Histologically confirmed invasive breast cancer with stage IV disease

          -  If trastuzumab was administered in the adjuvant setting, >12 months must have elapsed
             since discontinuation of trastuzumab therapy

          -  If a taxane was administered in the neoadjuvant or adjuvant setting, progression must
             have occurred ≥12 months after completion of this treatment

          -  Had tumors that overexpress ErbB2 defined as either: 3+ by IHC OR c-erbB2 gene
             amplification by FISH OR 0, 1+, 2+ by IHC and c-erbB2 gene amplification by FISH.

          -  Patients must have tumor tissue available for central testing, and must have
             Measurable lesion(s) according to RECIST

          -  Subjects must be females of at least 18 years Non-childbearing potential or
             Childbearing potential but using adequate contraception

          -  Radiotherapy to a limited area other than the sole site of measurable and assessable
             disease is allowed; however, patients must have completed treatment and recovered from
             all acute treatment-related toxicities prior to administration of the first dose of
             study medication

          -  Bisphosphonate therapy for bone metastases is allowed; however, treatment must be
             initiated prior to the first dose of randomized therapy. Prophylactic use of
             bisphosphonates in patients without bone disease is not permitted, except for the
             treatment of osteoporosis

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1

          -  For those patients whose disease is estrogen receptor positive+ and/or progesterone
             receptor + one the following criteria should be met: Patients with visceral disease
             that requires chemotherapy (eg., patients with liver or lung metastases) or Rapidly
             progressing/life threatening disease, as determined by the investigator or Patients
             who received hormonal therapy and are no longer benefiting from this therapy;

          -  Able to swallow and retain oral medication

          -  Cardiac ejection fraction within institutional range of normal

          -  Patient must have adequate organ function

        Exclusion criteria:

          -  Pregnant or lactating females;

          -  Received prior chemotherapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2
             therapy for metastatic disease, prior hormonal therapy is permitted but must be
             discontinued a minimum of 7 days prior to randomization;

          -  Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
             resection of the stomach or small bowel. Patients with ulcerative colitis are also
             excluded;

          -  History of other malignancy; however, patients who have been disease-free for five
             years, or patients 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 patient inappropriate for study
             participation, or any serious medical disorder that would interfere with the patient's
             safety;

          -  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;

          -  Active or 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, conduction
             abnormalities or congestive heart failure;

          -  Known history or clinical evidence of central nervous system (CNS) metastases or
             leptomeningeal carcinomatosis;

          -  Concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic
             therapy, hormonal therapy);

          -  Concurrent treatment with an investigational agent or participation in another
             clinical trial;

          -  Concurrent treatment with any medication on the prohibited medications list.

          -  Used an investigational drug within 30 days or 5 half-lives, whichever is longer,
             preceding the first dose of treatment. Hormonal therapy needs to be discontinued at
             least 7 days before the first dose of treatment.

          -  Prior therapy with an ErbB2 inhibitor, other than trastuzumab in the adjuvant setting;

          -  A known immediate or delayed hypersensitivity reaction to drugs chemically related to
             lapatinib or excipients;

          -  A known immediate or delayed hypersensitivity reaction to drugs chemically related to
             paclitaxel or excipients;

          -  A known immediate or delayed hypersensitivity reaction to drugs chemically related to
             trastuzumab or excipients;

          -  Non compliance with any of the screening procedures