Lapatinib in Combination With Vinorelbine
Condition: Cancer
Intervention: Vinorelbine; Lapatinib; Capecitabine
Intervention description: Vinorelbine; Lapatinib; Capecitabine
Intervention MeSH terms: Capecitabine; Vinorelbine; Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: After disease progression in the Randomized Phase (in which participants received lapatinib plus vinorelbine), participants were given the option of crossing over to the alternative treatment arm (lapatinib plus capecitabine), and continuing in a post-progression Cross-over Phase.
Masking: None (Open Label)
Enrollment: 112.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Neoplasms, Breast

Summary:

      This is a randomized, parallel-arm, open-label, multi-centre, Phase II study to determine the
      efficacy and safety of lapatinib in combination with vinorelbine or capecitabine in women
      with ErbB2 overexpressing metastatic breast cancer (MBC) who have received no more than one
      chemotherapeutic regimen in the metastatic setting.
    

Eligibility criteria:

        Inclusion Criteria :

          -  Signed informed consent prior to registration.

          -  Considered by the investigator to have a life expectancy of ≥12 weeks.

          -  Subjects must be female and have histologically - confirmed invasive breast cancer
             with Stage IV disease at primary diagnosis or at relapse after curative - intent
             surgery.

          -  Documented overexpression of ErbB2

          -  Subjects should have progressive disease following prior therapy which may include
             anthracyclines, taxanes, and trastuzumab.

          -  Females aged ≥18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1.

          -  Subjects must have adequate organ and marrow function

          -  Subjects must have a cardiac ejection fraction of at least 50% and within the
             institutional range of normal.

          -  Radiotherapy prior to initiation of study medication is allowed to a limited area ( e
             . g . , palliative therapy ) , if it is not the sole site of disease.

          -  Subjects with stable central nervous system (CNS) metastases are permitted.

          -  Subject must be free of gastrointestinal diseases or any other conditions that impede
             swallowing, retaining, and absorption of oral medications.

          -  Bisphosphonate therapy for bone metastases is allowed; however, treatment must be
             initiated prior to the first dose of study medication. Prophylactic use of
             bisphosphonates in subjects without bone disease, except for the treatment of
             osteoporosis, is not permitted.

        Exclusion Criteria:

          -  Subjects taking prohibited medications are not eligible for the study.

          -  Therapy with lapatinib, vinorelbine, or capecitabine prior to randomization into this
             study.

          -  Prior therapy with more than one chemotherapeutic regimen for metastatic breast
             cancer.

          -  Concurrent anticancer or concomitant radiotherapy treatment.

          -  History of uncontrolled or symptomatic angina; history of arrhythmias requiring
             medications ; clinically significant myocardial infarction < 6 months from study
             entry; uncontrolled or symptomatic congestive heart failure; ejection fraction below
             the institutional normal limit; or any other cardiac condition, which in the opinion
             of the treating physician, would make this protocol unreasonably hazardous for the
             patient.

          -  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).

          -  Use of an investigational drug within 30 days or 5 half - lives, whichever is longer,
             preceding the first dose of investigational treatment, or, concurrent treatment with
             an investigational agent or participation in another clinical trial involving
             investigational agents.

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to any of the agents used in this study or their excipients that in
             the opinion of the investigator or GSK Medical Monitor contraindicates their
             participation.

          -  Known deficiency for the enzyme dihydropyrimidine dehydrogenase (DPD).

          -  Known history of uncontrolled inter - current illness including, but not limited to,
             ongoing or active infection, symptomatic congestive heart failure, unstable angina
             pectoris, clinically significant cardiac arrhythmia, or psychiatric illness / social
             situations that would limit compliance with study requirements.

          -  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.

          -  Pregnant or lactating females at any time during the study (due to the potential
             teratogenic or abortifacient effects of lapatinib and breastfeeding).

          -  Subjects with diseases affecting gastrointestinal function resulting in an inability
             to take oral medication , including ; malabsorption syndrome, disease significantly
             affecting gastrointestinal function , or resection of the stomach , small bowel , or
             colon. Subjects with inflammatory bowel disease or ulcerative colitis are also
             excluded.

          -  Peripheral neuropathy of Grade 2 or greater.

          -  Unresolved or unstable, serious toxicity from prior administration of another
             investigational drug and / or of prior cancer treatment.

          -  Dementia, altered mental status, or any psychiatric condition that would prohibit the
             understanding or rendering of informed consent.