Phase I/II Study of Lapatinib in Combination With Paclitaxel as 1L Chemotherapy for ErbB2-positive MBC
Condition: Neoplasms, Breast
MeSH terms: Breast Neoplasms
Intervention: Lapatinib in combination with weekly paclitaxel
Intervention description: These subjects will receive weekly paclitaxel (80 mg/m2 IV for 3 weeks in a 4 week cycle) plus lapatinib (1500 mg once daily, starting on the second day of phase I). Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. Study completion is defined as deaths after administering study treatment for more than once. Subjects will be treated with paclitaxel for standard of 6 cycles, and may be continued at the discretion of investigators. If the subject experiences progression, an unacceptable toxicity related to paclitaxel, or termination of lapatinib therapy, paclitaxel therapy must be terminated any time of study period, even before 6 cycles of paclitaxel are given.
Intervention MeSH terms: Paclitaxel; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: advanced/metastatic breast cancer; lapatinib; ErbB2; ErbB2-overexpressing; pharmacokinetics; dual kinase inhibitor; HER-2/neu; EGFR; ErbB1

Summary:

      This is an open-label, non-randomized, multi-center study of lapatinib plus paclitaxel to
      evaluate safety, tolerability and efficacy in Japanese patients with ErbB2 over expressing
      advanced or metastatic breast cancer. Lapatinib 1500mg/day will be administered in
      combination with paclitaxel 80mg/m2/week. Lapatinib and paclitaxel will be administered until
      disease progression or withdrawal from the study due to unacceptable toxicity.

      The study will proceed in two phases. The first phase (Phase I part) will lead to evaluate
      safety and tolerability of lapatinib taken together with paclitaxel in the first 6 subjects.
      Pharmacokinetic profile also will be evaluated as the secondary objects.

      Then the study will move to the next treatment phase (Phase II part) to evaluate further
      safety and clinical activity, if no major safety concerns are raised during Phase I part. The
      primary objective of the study is to evaluate overall survival (OS), and the secondary
      objectives are Objective tumour response rate (ORR), Duration of response, Time to response,
      Clinical benefit and Progression-free survival (PFS) in 12 subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Prior written consent in participating in the study by the subject or his/her private
             attorney.

          -  Japanese female >=18 years of age.

          -  Invasive breast cancer with stage IV disease.

          -  Documentation by local laboratory of ErbB2 status by immunohistochemistry (IHC) or
             amplification by fluorescence in situ hybridization (FISH).

          -  If a taxane had been administered in the neoadjuvant or adjuvant setting, progression
             must have occurred >12 months after completion of this treatment and the patients
             recovered from all associated toxicities.

          -  Measurable lesion(s) according to RECIST criteria.

          -  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.

          -  For those patients whose disease is ER+ and/or PR+ one of the following criteria
             should be met:

               -  Patient with visceral disease that requires chemotherapy (e.g., patients with
                  liver or lung metastases).

               -  Rapidly progressing or life threatening disease that are considered to be
                  inapplicable to hormonal therapy, 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.

               -  Subjects recovered from all the associated toxicities by prior endocrine therapy.

          -  Eastern cooperative oncology group (ECOG) Performance status (PS) of 0 or 1.

          -  Able to swallow and retain oral medication.

          -  Cardiac ejection fraction within institutional range of normal as measured by
             echocardiogram. MUGA scan is accepted in cases where an echocardiogram cannot be
             performed or is inconclusive.

          -  Adequate organ function.

        Exclusion Criteria:

          -  Pregnant or lactating females at anytime during the study.

          -  Received prior chemotherapy, immunotherapy, biologic therapy or anti-ErbB1/ErbB2
             therapy for metastatic disease.

          -  History of other malignancy.

          -  Prior therapy with an ErbB1 and/or ErbB2 inhibitor, other than trastuzumab, in the
             adjuvant setting.

          -  Planned concurrent anti-cancer therapy (chemotherapy, radiation therapy,
             immunotherapy, biologic therapy, hormonal therapy) while taking investigational
             treatment.

          -  Used an investigational drug within 30 days or five half-lives, whichever is longer,
             preceding the first dose of investigational treatment.

          -  Unresolved or unstable, serious toxicity from prior administration of another
             investigational drug and/or of prior anti-cancer treatment.

          -  Uncontrolled infection.

          -  Patients having at least positive antibody either to HBs or HBc.

          -  Patients who have had a positive HCV antibody.

          -  Peripheral neuropathy 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.

          -  Dementia, altered mental status, or any psychiatric condition that would prohibit the
             understanding or rendering of informed consent.

          -  Known history or clinical evidence of central nervous system (CNS) metastases or
             leptomeningeal carcinomatosis.

          -  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.

          -  Known history or concurrent condition of uncontrolled or symptomatic angina,
             arrhythmias, or congestive heart failure.

          -  Concurrent treatment with prohibited medications.

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to paclitaxel or lapatinib or their excipients.

          -  Have current active hepatic or biliary disease (with exception of patients with
             Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver
             disease per investigator assessment).