Combination Chemotherapy With or Without Trastuzumab in Treating Women With Metastatic Breast Cancer
Condition: Recurrent Breast Cancer; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: pegylated liposomal doxorubicin hydrochloride; docetaxel; trastuzumab; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Given IV; Correlative studies
Intervention MeSH terms: Docetaxel; Doxorubicin; Liposomal doxorubicin; Trastuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 84.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Phase II trial to study the effectiveness of combination chemotherapy with or without
      trastuzumab in treating women who have metastatic breast cancer. Drugs used in chemotherapy
      use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal
      antibodies such as trastuzumab can locate tumor cells and either kill them or deliver
      tumor-killing substances to them without harming normal cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed adenocarcinoma of the breast with manifestations of
             metastatic progression

          -  HER2 expression status in primary breast tissue and/or site(s) of metastasis must be
             determined by the ECOG Pathology Coordinating Office; (these are the results that will
             be used at time of registration); NOTE: for this protocol, HER2/neu non-overexpressed
             status will be defined as 0 and 1+ scores using the DAKO HercepTest; HER2
             overexpressed status will be defined as 2+ score (if confirmed amplified by FISH) or
             3+ score using the DAKO HercepTest

          -  Cytologically positive pleural or peritoneal effusions are considered evaluable
             disease provided local intra-cavitary treatment is not introduced at the onset of
             therapy; to be considered as evaluable disease, pleural effusions may not have been
             previously drained or sclerosed

          -  Blastic or mixed blastic/lytic osseous metastases only are evaluable disease provided
             they are accompanied by an analgesic requirement or a decrease in performance status,
             and will not require radiation treatment within two cycles from the start of protocol;
             pure osteolytic disease is evaluable; bone disease must be x-ray proven for the site
             to be evaluable; patients whose only evidence of metastatic disease is an abnormal
             bone scan without confirmatory x-rays are not eligible for this study

          -  No prior chemotherapy for advanced disease; prior adjuvant chemotherapy (including
             taxanes) allowed, if completed > 6 months before the diagnosis of metastatic disease;
             no prior adjuvant anthracycline, nor any prior exposure to other anthracycline- (e.g.,
             epirubicin, any liposomal doxorubicin formulation), nor any anthracenedione- (e.g.,
             mitoxantrone) containing regimen allowed; no prior therapy with Herceptin allowed;
             NOTE: chemotherapy after ipsilateral breast recurrence following breast conservation
             surgery would not be considered chemotherapy for advanced disease; however, in
             post-mastectomy patients chemotherapy for local/regional recurrence is considered
             treatment for advanced disease

          -  No prior radiotherapy other than to the conserved breast, to the post-mastectomy chest
             wall, or to a limited field involving < 25% of marrow-containing bone; NOTE: previous
             post-mastectomy radiation therapy involving chest wall ± internal mammary lymph node
             chain (IMN) is allowed; however, patients who received photon IMN treatment are
             ineligible; NOTE: radiotherapy must be completed >= 2 weeks prior to registration; it
             may not be given concurrently with Doxil, Taxotere, or Herceptin

          -  Prior hormonal therapy in either a metastatic or adjuvant setting is allowed, but
             patients must have been off such therapy for >= 2 weeks prior to registration

          -  Disease-free of prior non-breast invasive malignancies for >= 5 years with the
             exception of curatively-treated basal cell or squamous cell carcinoma of the skin or
             carcinoma in situ of the cervix

          -  ECOG performance status of 0, 1, or 2

          -  At least two weeks after any major surgery (including mastectomy) and recovered from
             all toxicity

          -  Creatinine =< 1.5 mg/dl

          -  Granulocytes >= 1,500/mm³

          -  Platelets >= 100,000/mm³

          -  SGOT(AST) =< 2.5 x the upper limit of normal

          -  Bilirubin within normal limits for institution

          -  No history of deep venous thrombosis, pulmonary thromboembolism, or other
             thromboembolic condition

          -  Women must not be pregnant or breastfeeding; the effect of Herceptin to the fetus is
             unknown; Doxil is known to be harmful to the fetus

          -  Women of childbearing potential must be advised to use an accepted and effective
             method of contraception

          -  No patients with untreated brain metastasis or brain metastasis undergoing radiation
             or for whom brain metastasis represent the sole site of disease; patients with
             previously treated brain metastasis who have responded to brain radiotherapy and/or
             surgery and continue in response are eligible, provided the brain is not the only site
             of disease

          -  The left ventricular ejection fraction must be at or above the lower institutional
             limits of normal (as assessed by MUGA scan or echocardiogram obtained within six weeks
             prior to registration); patient will not be eligible if baseline LVEF assessment not
             performed

          -  No prior history of myocardial infarction, congestive heart failure, or arrhythmia
             requiring medication; no history of hypertension or systolic or diastolic dysfunction;
             no EKG evidence of ventricular hypertrophy, conduction abnormality, or serious
             arrhythmia; patient will not be eligible if baseline EKG assessment not performed
             within 4 weeks