Cetuximab + / - Carboplatin for Estrogen Receptor-Negative, Progesterone Receptor-Negative Metastatic Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: cetuximab; carboplatin
Intervention description: Given IV; Given IV
Intervention MeSH terms: Carboplatin; Cetuximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 112.0
Sex: Female
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: recurrent breast cancer; stage IV breast cancer

Summary:

      RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different
      ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and
      help kill them or carry tumor-killing substances to them. Cetuximab may also stop the growth
      of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in
      chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells,
      either by killing the cells or by stopping them from dividing. It is not yet known whether
      giving cetuximab together with carboplatin is more effective than giving cetuximab alone in
      treating metastatic breast cancer.

      PURPOSE: This randomized phase II trial is studying cetuximab and carboplatin to see how well
      they work compared with cetuximab alone in treating women with estrogen receptor-negative
      (ER-), progesterone receptor-negative (PR-) metastatic breast cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed breast cancer

               -  Metastatic (stage IV) disease

          -  Measurable disease by RECIST criteria

               -  Irradiated lesions are not considered measurable disease

          -  Central nervous system (CNS) metastases allowed if disease is stable (no evidence of
             progression) ≥ 3 months after local therapy

          -  No lesions identifiable only by positron emission tomography (PET) scan

          -  HER2 nonoverexpressing disease by IHC (0 or 1) or non-gene amplified by Fluorescence
             In Situ Hybridization (FISH)

               -  HER2 2+ by IHC allowed

          -  Hormone receptor status:

               -  Estrogen receptor-negative and progesterone receptor-negative tumor

        Inclusion Criteria

          -  At least 18 years of age

          -  Metastatic breast cancer (Stage IV) with measurable disease by RECIST criteria

          -  No more than three prior chemotherapy regimens either in the adjuvant or metastatic
             setting.

          -  Histologically documented (either primary or metastatic site) breast cancer that is
             estrogen receptor- (ER-) negative, PR-negative, and HER-2 nonoverexpressing by
             immunohistochemistry (0,1) or non-gene amplified by FISH performed upon the primary
             tumor or metastatic lesion. HER-2 2+ by immunohistochemistry is usually negative by
             FISH, and this confirmatory test should be performed when possible, however may
             participate if fulfill other criteria.

          -  Completion of prior chemotherapy at least 3 weeks prior to study entry.

          -  Patients may have received therapy (ies) in the adjuvant or metastatic setting,
             however must have discontinued prior to entry. Patients may receive concurrent
             bisphosphonates, however if taking bisphosphonates, bone lesions may not be used for
             progression or response.

          -  Radiation therapy must be completed at least 2 weeks prior to study entry, and
             radiated lesions may not serve as measurable disease.

          -  Patients may have CNS metastases if stable (no evidence of progression) > 3 months
             after local therapy.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and life expectancy
             of at least 6 months.

          -  Adequate organ function defined as:absolute neutrophil count (ANC) > 1500/mm3, plts >
             100,000/mm3, creatinine clearance >50 mL/min, alanine aminotransferase (ALT) and
             aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN) (or ≤5 x ULN in
             case of liver metastases); total bilirubin ≤1.5 mg/dL.

          -  Tissue block available for EGFR studies is recommended, although will not exclude
             patients from participating.

          -  Pregnant or lactating women will be excluded. Women of child bearing potential must
             have documented negative pregnancy test within two weeks of study entry and agree to
             acceptable birth control during the duration of the study therapy.

          -  Signed written informed consent.

        Exclusion Criteria

          -  Lesions identifiable only by PET.

          -  More than three prior chemotherapy regimens (including adjuvant). Sequential regimens
             such as doxorubicin and cyclophosphamide followed by paclitaxel (AC-paclitaxel) are
             considered one regimen.

          -  Prior therapy which specifically and directly targets the EGFR pathway with
             therapeutic intent.

          -  Prior platinum agent for metastatic disease. If platinum agent was used adjuvantly,
             the patient must have had at least 12 months disease-free interval prior to relapse.

          -  Prior severe infusion reaction to a monoclonal antibody.

          -  Major medical conditions that might affect study participation (uncontrolled
             pulmonary, renal, or hepatic dysfunction, uncontrolled infection).

          -  Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension,
             unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled
             congestive heart failure, and cardiomyopathy that is either symptomatic or
             asymptomatic but with decreased ejection fraction <45%

          -  Other significant comorbid condition which the investigator feels might compromise
             effective and safe participation in the study.

          -  Inability to comply with the requirements of the study.