Ixabepilone + Carboplatin Metastatic Breast Cancer
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Ixabepilone; Carboplatin
Intervention description: 20 mg/m2 on Days 1 and 8; carboplatin AUC=2.5 on Days 1 and 8
Intervention MeSH terms: Carboplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 103.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: metastatic; breast; cancer

Summary:

      Ixabepilone adds significantly to the antitumor effectiveness of capecitabine in both ER+ and
      triple negative breast cancer. Ixabepilone has substantial antitumor activity in
      taxane-refractory patients and novel combinations are needed in this poor prognosis
      population. Carboplatin in combination with gemcitabine or paclitaxel has activity in
      metastatic breast cancer (MBC); there is also demonstrated activity of the
      gemcitabine/carboplatin combination in the ER+ versus triple negative subsets. A Phase I
      study of ixabepilone plus carboplatin in solid tumor patients demonstrated the safety of this
      combination at the doses and schedule proposed for this Phase II trial (BMS data on file).
    

Eligibility criteria:

        Inclusion Criteria:

        Male or female patients will be eligible for inclusion in this study if they meet all of
        the following criteria:

          1. Has measurable metastatic and or locally unresectable breast cancer with documented
             HER2 negative (-) disease

          2. Has at least 1 measurable lesion per RECIST criteria (lesions that can be accurately
             measured in at least 1 dimension (longest diameter (LD) to be recorded) as ≥20 mm with
             conventional techniques (CT, MRI, X-ray) or as ≥10 mm with spiral CT scan). Irradiated
             lesions cannot be used to assess response but can be used to assess progression.

          3. Has received up to 2 (0 to 2) prior chemotherapy regimens for metastatic disease with
             the following conditions:

             •Has had no prior treatment with ixabepilone or platinum agents

          4. Has had no adjuvant chemotherapy within the 6 months prior to study, but may have
             received prior anthracyclines and/or taxanes as adjuvant chemotherapy

          5. 3 weeks or more have elapsed since last chemotherapy treatment and any related
             toxicities have resolved to <Grade 1; at least 30 days must have passed since any
             investigational product has been administered and associated toxicities must have
             resolved to <Grade 1 (if applicable).

          6. Has an ECOG Performance Status (PS) 0-2

          7. Is ≥18 years of age

          8. Has a life expectancy of at least 12 weeks

          9. Has laboratory values of:

             White blood cell (WBC) count ≥3000 x 106/L Absolute neutrophil count (ANC) ≥1500 x
             106/L Hemoglobin ≥9 g/dL Total bilirubin ≤1x upper limit of normal (ULN) AST and ALT
             ≤2.5 x ULN Alkaline phosphatase ≤2.5 x ULN; up to 5xULN if elevation is due to bone
             disease Serum creatinine ≤1.5 mg/dL Calculated creatinine clearance >50 mL/min (based
             on Cockroft and Gault method [Appendix III]) Platelet count ≥100,000 x 106/L

         10. If patient has had radiation therapy, it has been completed >3 weeks prior to the
             start of study treatment. NOTE: Previously irradiated lesions will not be evaluable.
             However, these patients will still be eligible.

         11. Has a negative serum pregnancy test within 7 calendar days prior to registration
             (female patients of childbearing potential [not surgically sterilized and between
             menarche and 1 year postmenopause

         12. 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 3 months
             thereafter

         13. Has signed the most recent Patient Informed Consent Form

         14. Has signed a Patient Authorization Form Note: Having tissue available is not an
             inclusion criterion in this study; however, available tissue will be collected (see
             Section 8) if possible.

        Exclusion Criteria:

        A patient will be excluded from this study if he or she meets any of the following
        criteria:

          1. Had prior treatment with ixabepilone or other epothilones

          2. Had prior radiation to ≥30% of major bone marrow containing areas (pelvis, lumbar
             spine)

          3. Has ER+ and/or PR+ disease that has not progressed on hormone therapy, unless the
             patient has life-threatening or rapidly progressing visceral disease

          4. Has HER2+ disease (IHC staining of 3+ [uniform, intense membrane staining of >30% of
             invasive tumor cells]), a FISH result of more than 6 HER2 gene copies per nucleus or a
             FISH ratio (HER2 gene signals to chromosome 17 signals of >2.2)

          5. Has only lytic bone disease or nonmeasurable disease only

          6. Has a known, prior, severe (NCI CTCAE Grade 3-4) history of hypersensitivity reaction
             to a drug formulated in Cremophor®EL (polyoxyethylated castor oil) or has history of
             severe allergic reactions to cisplatin or other platinum-containing compounds

          7. Has been treated previously with a platinum-containing agent

          8. Is receiving concurrent immunotherapy, hormonal therapy, or radiation therapy. Washout
             periods for these prior therapies are specified in Section 5.

          9. Is receiving concurrent investigational therapy or has received such therapy within
             the 30 days prior to dosing Day 1

         10. Has neuropathy (motor or sensory) >Grade 1

         11. Has evidence of CNS involvement requiring radiation or steroid treatment. Patients
             with stable brain metastases who are off steroids at least 2 weeks are eligible.

         12. Has a serious uncontrolled intercurrent medical or psychiatric illness, including
             serious infection

         13. Has clinically relevant coagulopathy either secondary to hepatic dysfunction or an
             underlying condition requiring therapeutic anticoagulation (specifically, A-fib,
             history of DVT). A daily aspirin or Plavix for CAD are permitted.

         14. 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

         15. Is a pregnant or breast feeding woman

         16. Is unable to comply with the requirements of the study