Randomized Phase II Study of Weekly Irinotecan/Carboplatin (ICb) With or Without Cetuximab (Erbitux) in Patients With Metastatic Breast Cancer

Inclusion Criteria

INCLUSION CRITERIA:

Male and female patients will be eligible for inclusion in this study if they meet all of
the following criteria:

- Has cytologically or pathologically confirmed, breast cancer with documented HER2+
(positive) (3+ by IHC or FISH+) or HER2- (negative) disease. ER, PR, and HER2 status
must be documented in the electronic Case Report Form (eCRF) NOTE: Patients whose
breast cancers are HER2 (2+) by IHC must undergo FISH testing to confirm HER2+
(positive) status.

- Has clinically confirmed Stage IV metastatic breast cancer (MBC)

- Has undergone prior Herceptin therapy if breast cancer is HER2+ (positive)

- Has measurable MBC as defined by the Response Evaluation Criteria in Solid Tumors
(RECIST) Criteria

NOTE: Ascites, pleural effusion, and bone metastases are not considered measurable.

- Has had up to 1 prior chemotherapy regimens for metastatic disease. Previously
untreated disease is permitted.

- Has had no prior treatment with irinotecan, carboplatin, or cisplatin

- Has an ECOG Performance Status (PS) 0-2

- Is greater than 18 years of age

- Please see protocol for specific details regarding appropriate laboratory values for
inclusion to the study.

- Any prior radiation therapy has been completed > 2 weeks prior to the start of study
treatment

NOTE: Previously irradiated lesions will not be evaluable; however, these patients will
still be eligible. Patients must have at least 1 measurable lesion at baseline.

- Has had a negative serum pregnancy test within 7 days prior to registration (female
patients of childbearing potential). A pregnancy test is also required within 7 days
of Dose 1.

- If fertile, patient (male or female) has agreed to use an acceptable method of birth
control to avoid pregnancy for the duration of the study and for a period of 6 months
thereafter.

- Has signed a Patient Informed Consent Form

- Has signed a Patient Authorization Form (HIPAA)

- Has paraffin-embedded breast cancer tissue (either paraffin blocks or 20 unstained
slides) available for analysis of EGFR, cytokeratin, and other biological markers.
These samples will be sent to the Molecular Profiling Institute (MPI; see Appendix
VII).

NOTE: Availability of samples should be confirmed prior to randomization (at latest, prior
to first dose).

EXCLUSION CRITERIA:

- Has Stage I-III breast cancer or nonmeasurable metastatic breast cancer, or any
disease other than that described in inclusion criterion #1

- Has received prior treatment with irinotecan, carboplatin, or cisplatin

- Is receiving any concurrent chemotherapy not indicated in the study protocol or any
other investigational agent(s)

- Has received prior therapy which specifically and directly targets the EGFR pathway.
Prior Herceptin is required for HER2+ patients.

- Has had prior severe infusion reaction to a monoclonal antibody

- Has received organ allograft(s) other than corneal, bone, or skin

- Has clinically significant uncontrolled cardiac disease (eg, congestive heart
failure, symptomatic coronary artery disease or cardiac arrhythmias not
well-controlled with medication) or has had a myocardial infarction < 12 months

- Has ongoing peripheral neuropathy > Grade I

- Has evidence of symptomatic or untreated central nervous system (CNS) metastases
(unless CNS metastases have been irradiated). Chronic steroid treatment for the
treatment of CNS metastases must have been discontinued for greater than 4 weeks
prior to study enrollment.

- Has any other significant comorbidity that, in the opinion of the clinical
investigator, might compromise any aspect of the study

- Has active or uncontrolled infection

- Has acute hepatitis or is known to be HIV positive

- Has a history of other malignancy within the last 5 years which could affect the
diagnosis or assessment of MBC, with the exception of carcinoma of the cervix in
situ, carcinoma of the bladder in situ, and basal cell carcinoma

- Has previously completed a chemotherapy regimen within 3 weeks prior to the start of
study treatment, or has related toxicities unresolved prior to the start of study
treatment

NOTE: If patient was receiving prior weekly or daily chemotherapy, he/she may begin study
therapy 2 weeks after stopping prior therapy provided all toxicities have resolved;
peripheral neuropathy must be less than Grade I as per exclusion criterion #8 above.

- Has had major surgery within 3 weeks from the start of study treatment, without
complete recovery

- Has participated in any investigational drug study within 4 weeks preceding the start
of study treatment

- Has received a concurrent immunotherapy or hormonal anticancer agent within 2 weeks
prior to the start of the study treatment

- Is receiving a tyrosine kinase inhibitor (ie, IressaTM)

- Has had any prior stem cell or bone marrow transplant for any prior hematologic
malignancy

- Is pregnant or lactating

- Is unable to comply with the requirements of the study