Phase II Study of Doxil and Carboplatin, Plus Herceptin in HER2+ Patients, in Metastatic Breast Cancer

Inclusion Criteria:

- Has metastatic breast cancer with documented HER2- or HER2+ (IHC3+ or FISH+) disease

- Has measurable MBC, with at least 1 measurable lesion per RECIST criteria (see
Section 10). Irradiated lesions cannot be used to assess response but can be used to
assess progression.

- Has had no prior treatment with Doxil or carboplatin; may have had adjuvant Herceptin
if treatment was completed more than 1 year prior to study

- Has had no adjuvant chemotherapy within 1 year prior to study, but may have received
prior anthracyclines as adjuvant chemotherapy

- For taxane-pretreated patients (adjuvant or metastatic), has had no more than 1 prior
chemotherapy regimen for MBC

- For taxane-naïve patients, has had no prior chemotherapy for MBC

- Has had cumulative doses of < 300 mg/m2 prior doxorubicin or < 450 mg/m2 prior
epirubicin

- Has normal cardiac function as evidenced by a LVEF within institutional normal limits
by multiple gated acquisition (MUGA) scan. An echocardiogram (ECHO) may be used if
MUGA is not available, but the same test must be used throughout the study to
evaluate LVEF.

- Has an ECOG Performance Status (PS) 0-2 (see Appendix I)

- Is a male or female greater than or equal to 18 years of age

- Laboratory Values - Please refer to protocol section 4.2 for specific laboratory
values.

- Has a negative serum pregnancy test within 7 days prior to registration (woman of
childbearing potential [WOCBP; not surgically sterilized and between menarche and 1
year postmenopause])

- If fertile, patient (male or female) has agreed to use an acceptable method of birth
control (eg, abstinence, intrauterine device, oral contraceptives, barrier device
with spermicide or surgical sterilization) to avoid pregnancy for the duration of the
study and for a period of 3 months thereafter.

- Has signed a Patient Informed Consent Form

- Has signed a Patient Authorization Form (HIPAA Form)

- Has a life expectancy of > 3 months

Exclusion Criteria:

- Has had a myocardial infarction (MI) within 6 months of trial enrollment, or has New
York Heart Association (NYHA; see Appendix IV) Class II or greater heart failure,
uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically
significant pericardial disease, or electrocardiographic evidence of acute ischemic
or active conduction system abnormalities

- Has a history of hypersensitivity reactions attributed to a conventional formulation
of doxorubicin HCL or the components of Doxil

- Has evaluable only disease; eg, bone only, pleural, peritoneal only disease

- Is receiving concurrent immunotherapy, hormonal therapy, or radiation therapy.
Patients receiving immunosuppressant therapy for autoimmune disease may enroll on the
trial after a drug washout period of 2 weeks.

- Is receiving concurrent investigational therapy or has received such therapy within
30 days

- Has evidence of brain metastases requiring steroids and/or radiation or any
documented leptomeningeal disease

- Has a serious uncontrolled intercurrent medical or psychiatric illness, including
serious infection or history of uncontrolled seizures, CNS disorders deemed by the
Treating Physician to be clinically significant, precluding informed consent

- Has a history of other malignancy within the last 5 years (except cured basal cell
carcinoma of skin and carcinoma in situ of uterine cervix), which could affect the
diagnosis or assessment of any of the study drugs

- Is a pregnant or lactating woman

- Is unable to comply with requirements of study