Panitumumab, Gemcitabine and Carboplatin in Triple-Negative Metastatic Breast Cancer
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Panitumumab; Carboplatin; Gemcitabine
Intervention description: 6 mg/kg IV on Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks); AUC=2.5 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks); 1500 mg/m2 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)
Intervention MeSH terms: Carboplatin; Gemcitabine; Panitumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 71.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Breast Cancer; Triple Negative; Panitumumab; Vectibix; Gemcitabine; Gemzar; Carboplatin

Summary:

      In this Phase II trial, the investigators will evaluate the combination of gemcitabine,
      carboplatin, and panitumumab in the treatment of patients with metastatic triple-negative
      breast cancer. In addition, to assess the efficacy of this combination, tumor tissue will be
      examined for the presence of various markers, including K-ras and PI3K-activating mutations,
      EGFR, PTEN, and p53. Correlation of tumor response with marker expression may define a
      patient subset that is particularly responsive to treatment with a panitumumab-containing
      combination.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Female patients >=18 years of age.

          2. Histologically or cytologically confirmed diagnosis of unresectable locally advanced
             or stage IV breast cancer.

          3. No more than 1 prior treatment regimen for metastatic breast cancer.

          4. Estrogen receptor and progesterone receptor negative (defined as <10% staining by
             IHC).

          5. Paraffin-embedded tumor tissue (from the primary tumor or metastasis) for biomarker
             testing. (In the absence of paraffinembedded tissue, unstained paraffin-embedded tumor
             slides are acceptable).

          6. Measurable disease, as defined by the Response Evaluation Criteria in Solid Tumors
             (RECIST version 1.1) guidelines

          7. HER2 negative tumors. HER2 negativity must be confirmed by one of the following:

               -  FISH-negative (FISH ratio <2.2), or

               -  IHC 0-1+, or

               -  IHC 2-3+ AND FISH-negative (FISH ratio <2.2)

          8. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1.

          9. Absolute neutrophil count (ANC) >=1.5 × 109/L; platelet count >=100 × 109/L;
             hemoglobin >=9.0 g/dL.

         10. Creatinine <=1.5 mg/dL, or creatinine clearance >=40 mL/min (as calculated by the
             Cockcroft-Gault method, as follows: Female creatinine clearance = (140 - age) ×
             (weight in kg) × 0.85 (serum creatinine × 72)

         11. Adequate hepatic function, defined as follows: total bilirubin <=1.5 x ULN; aspartate
             aminotransferase (AST) <=3 × ULN (or <= 5 x ULN if liver metastases); alanine
             aminotransferase (ALT) <=3 x ULN (or <=5 x ULN if liver metastases).

         12. Magnesium level >= the institutional lower limit of normal (LLN).

         13. Women of childbearing potential must agree to use adequate contraception (per
             institutional standard of care) during treatment and until 6 months after the last
             administration of investigational products.

        Exclusion Criteria:

          1. Patients with brain metastases are not eligible.

          2. History of another primary cancer, with the exception of the following:

               -  Curatively treated in situ cervical cancer;

               -  Curatively resected non-melanoma skin cancer;

               -  Other primary solid tumor curatively treated with no known active disease present
                  and no treatment administered for >=5 years prior to study enrollment.

          3. History of interstitial lung disease (e.g., pneumonitis, pulmonary fibrosis), or any
             evidence of interstitial lung disease on the CT scan of the chest performed at the
             baseline visit.

          4. Prior anti-EGFR antibody therapy (e.g., cetuximab), or treatment with small-molecule
             EGFR inhibitors (e.g., gefitinib, erlotinib, lapatinib).

          5. Radiotherapy <=14 days prior to study enrollment. Any acute effects of radiotherapy
             must be resolved prior to the administration of study drugs.

          6. Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved
             proteins/antibodies (e.g., bevacizumab) <=21 days prior to study enrollment.

          7. Prior therapy with gemcitabine or carboplatin in the metastatic setting is not
             permitted. Patients who received gemcitabine or carboplatin as part of adjuvant
             therapy are eligible, as long as recurrence was first documented >12 months after the
             last exposure to the drug(s).

          8. Major surgery within 28 days or minor surgery within 14 days of study enrollment.

          9. Requirement of chronic use of immunosuppressive agents (e.g., methotrexate,
             cyclosporine).

         10. Any investigational agent or therapy <=30 days prior to study enrollment.

         11. Uncontrolled or intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
             arrhythmia.

         12. History of any medical or psychiatric condition or laboratory abnormality that, in the
             opinion of the investigator, may increase the risks associated with the study
             participation or administration of the investigational products, or that may interfere
             with the interpretation of the results.

         13. Unwillingness or inability to comply with study requirements.

         14. Women who are pregnant or breastfeeding.

         15. Patients with known human immunodeficiency virus (HIV), hepatitis C virus, and/or
             acute or chronic hepatitis B virus infection.