PhII ICb With/Without Erbitux in MBC Pts
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Irinotecan + Carboplatin; irinotecan + Carboplatin + erbitux
Intervention description: irinotecan 90 mg/m2 and carboplatin AUC=2.0 on Days 1 and 8 of each 21-day cycle; irinotecan 90mg/m2, carboplatin AUC=2.0 on Days 1 and 8 of each 21- day cycle plus Erbitux 400 mg/m2
Intervention MeSH terms: Carboplatin; Irinotecan; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 154.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine the objective response rates produced by irinotecan
      and carboplatin therapy with or without Erbitux in patients with Metastatic Breast Cancer.
    

Eligibility 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