The Efficacy and Safety of Pegylated Liposomal Doxorubicin Compared With Capecitabine as First Line Chemotherapy for Metastatic Breast Cancer (P04445/MK-2746-071)
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Pegylated liposomal doxorubicin (SCH 200746); Capecitabine
Intervention description: pegylated liposomal doxorubicin (50 mg/m^2 q 28 days) was administered intravenously until disease progression or unacceptable toxicity; capecitabine (1250 mg/m^2 BID x 14 days q 21 days) in tablets of 150 mg and 500 mg was administered orally, until disease progression or unacceptable toxicity
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin; Capecitabine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 210.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is an open-label, multinational, randomized, multicenter trial designed to compare
      pegylated liposomal doxorubicin with capecitabine as first line chemotherapy of metastatic
      breast cancer. The primary objective of the study is to compare the time to disease
      progression, although overall response rates, overall survival, quality of life, time to
      treatment failure, and safety and tolerability will also be assessed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must be female.

          -  Patients must have metastatic disease of a cytological or histological confirmed
             breast cancer.

          -  Patients must be 18 years or older.

          -  Patients should have evaluable disease (at least uni-dimensionally measurable lesion
             according to the RECIST criteria in at least one site that has not been irradiated),
             however, patients who only have non-measurable/evaluable disease are not excluded.
             Also patients with only bone metastasis are not excluded.

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) 0-2.

          -  Patients must have a sufficient life expectancy to be treated with chemotherapy.

          -  Patients must be willing and able to complete study questionnaires.

          -  Patients must have adequate renal function as evidenced by serum creatinine <=1.5
             mg/dL, or a creatinine clearance of >=45 mL/min (if serum creatinine is > 1.5 mg/dL
             but <= 1.8 mg/dL).

          -  Patients must have adequate bone marrow function as evidenced by leukocyte count
             greater than 3.5 g/L, hemoglobin >=9.0 g/dL, and platelet count >=100x10^9/L.

          -  Patients must have adequate liver function as evidenced by bilirubin of <=1.5 times
             the upper limits of normal (ULN) and alkaline phosphatase <=3 times, ULN unless
             related to liver metastasis.

          -  Patients must have Sodium and Potassium values within normal limits.

          -  Patients whose clinical condition (co-morbidity) allows a treatment with monotherapy
             or who expressed their wish to be treated with monotherapy.

          -  Patients must have signed an informed consent document indicating that they understand
             the purpose of and procedures required for the study and are willing to participate in
             the study.

        Exclusion Criteria:

          -  History of receiving prior chemotherapy in the metastatic setting (Note: patients may
             have had

        hormonal therapy or chemotherapy in the adjuvant setting; patients may have received
        hormonal therapy in metastatic setting, patients may have received local radiotherapy).

          -  Patients with positive estrogen- / progesterone-receptor status, where an endocrine
             therapy is indicated. However, patients progressing under hormonal therapy are not
             excluded.

          -  Patients with known hypersensitivity to doxorubicinhydrochlorid or to any of the
             excipients OR known hypersensitivity to capecitabine or fluorouracil or to any of the
             excipients.

          -  Patients with known DPD (dihydro pyrimidine dehydrogenase) deficiency.

          -  Patients who are receiving a concomitant treatment with sorivudine or its chemically
             related analogues, such as brivudine.

          -  Patients who are taking concomitant medications (except bisphosphonates) for
             metastatic disease, including hormonal therapy, radiation therapy, trastuzumab, or
             biologicals are also not permitted.

          -  Patients with Human epidermal growth factor receptor 2 (Her-2/neu) overexpressing
             tumors with the most recent evaluation as the relevant result

               -  immunologically Her2neu 3+ positive

               -  Her2neu-2+ positive and ´Fluorescent in-situ hybridization (FISH)´ positive

          -  History of treatment with capecitabine

          -  History of treatment with anthracyclines in the adjuvant setting exceeding cumulative
             doses of anthracyclines by more than 360 mg/m^2 doxorubicin (or equivalents, i.e.
             600mg/m^2 epirubicine).

          -  Patients with anthracycline resistant disease are not permitted. Anthracycline
             resistance is defined as development of locally recurrent or metastatic disease while
             on adjuvant anthracycline therapy, or relapse less than 12 months after completion of
             anthracycline therapy.

          -  Strong remission pressure that requires polychemotherapy with the exception of
             patients who are not suitable for a treatment with polychemotherapy or not accepting
             polychemotherapy.

          -  Evidence of primary or metastatic malignancy involving the central nervous system
             unless previously treated and asymptomatic for 3 months or greater.

          -  Patients with reduced liver functions (evidenced by bilirubin of above 1.5 times the
             upper limits of normal (ULN); alkaline phosphatase above 3 times ULN (except related
             to liver metastasis, in which case <=5 x ULN).

          -  Dyspnea on exertion.

          -  History of cardiac disease, with New York Heart Association Class II or greater, or
             clinical evidence of congestive heart failure or myocardial infarct within less than
             six months or an left ventricular ejection fraction (LVEF) below 50%.

          -  Woman with childbearing potential with insufficient contraception [e.g. intra-uterine
             device (IUD) are regarded as sufficient] during the study period and the six months
             following the last study drug application. All methods based on hormonal contraception
             are not permitted.

          -  Existing pregnancy or lactation (note on pregnancy test). A negative pregnancy test
             for women of childbearing potential has to be in place prior randomization (Note: A
             pregnancy test has to be done for patients who are not postmenopausal. Postmenopausal
             is defined as those not having a menstrual period for 12 months in a row).

          -  Existing doubts on ability and willingness of the subject for cooperation.

          -  Participation of the subject at a clinical study within the last 30 days.

          -  Participation of the subject in the same clinical study at an earlier date.

          -  Concomitant participation in another study than the one described here.

          -  Abuse of drugs, alcohol, or pharmaceuticals.

          -  Any condition, whether medical or non-medical, that may interfere, in the opinion of
             the investigator, with aim of this study.