Chloroquine With Taxane Chemotherapy for Advanced or Metastatic Breast Cancer After Anthracycline Failure (CAT)
Condition: Breast Neoplasms; Breast Cancer
MeSH terms: Breast Neoplasms; Neoplasms
Intervention: Paclitaxel; Docetaxel; Abraxane; Ixabepilone
Intervention description: Chloroquine 250mg po daily together with Paclitaxel (Taxane) 175 mg/m2 three hours infusion every three weeks.; Chloroquine 250mg po daily together with docetaxel 75 mg/m2 administered intravenously over one hour every three weeks; Chloroquine 250mg po daily together with Abraxane 260 mg/m2 administered intravenously over 30 minutes every three weeks.; Chloroquine 250mg po daily together with Ixabepilone is 40 mg/m2 administered intravenously over three hours every three weeks.
Intervention MeSH terms: Paclitaxel; Docetaxel; Albumin-Bound Paclitaxel; Taxane
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Cancer; Breast Tumors; Cancer of Breast; Cancer of the Breast; Human Mammary Carcinoma; Mammary Carcinoma, Human; Mammary Neoplasm, Human; Mammary Neoplasms, Human; Neoplasms, Breast; Tumors, Breast; Chloroquine; Paclitaxel; Taxol; Ixabepilone; Abraxane; Metastatic Breast Cancer; Advanced Breast Cancer; Anthracycline

Summary:

      The major purpose of this research study is to better understand how therapy works on
      different patients. This study is being offered to patients with a diagnosis of advanced or
      metastatic breast cancer who have failed anthracycline based therapy.

      The investigators want to see the response of breast cancer cell when treated with
      Chloroquine used in combination with chemotherapy. Chemotherapy is an anti-cancer drug that
      is given through your vein. The chemotherapy used in this study is either Taxane (Paclitaxel)
      or Taxane-like drugs (Abraxane, Ixabepilone or Docetaxel).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Females with pathologically determined advanced or metastatic breast cancer.

          2. Have progressed after treatment with regimen that included an anthracycline.

          3. Have had at least 4 cycles of an anthracycline containing regimen or 2 cycles if
             progressing on treatment.

          4. Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors.

          5. ≥18 years of age.

          6. ECOG PS of 0, 1, or 2.

          7. Laboratory values within the following ranges:

               -  Hemoglobin ≥9.0gm/dL (≥1.5μmol/L); transfusions permitted.

               -  Absolute neutrophil count ≥1500/mm3 (1.5 x 109/L)

               -  Platelet count ≥100,000/mm3 (100 x 109/L)

               -  Creatinine (Cr) <2 X the upper limit of normal (ULN), Cr clearance (CrCl) ≥30 by
                  Cockcroft and Gault

               -  Alanine aminotransferase and aspartate aminotransferase <2 X the ULN; if liver
                  metastases are present then must be <5 X the ULN, Bilirubin <2 X the ULN,
                  Potassium within normal limits, Magnesium within normal limits

          8. Negative serum pregnancy test at the time of first dose for women of childbearing
             potential (WOCBP). For WOCBP, adequate contraception must be used throughout the
             study. For this study, acceptable methods of contraception include a reliable
             intrauterine device or a spermicide in combination with a barrier method. Women who
             are already on hormonal forms of birth control may continue that treatment but must
             also use a barrier method.

          9. Ability to understand the requirements of the study, provide written informed consent
             and authorization of use and disclosure of protected health information, and agree to
             abide by the study restrictions and return for the required assessments.

         10. Patient must be willing to undergo breast biopsies as required by the study protocol.

        Exclusion Criteria:

          1. Radiation therapy within 2 weeks; or chemotherapy or non-cytotoxic investigational
             agents within 4 weeks of initiating study treatment.

          2. Evidence of New York Heart Association class III or greater cardiac disease.

          3. History of myocardial infarction, stroke, ventricular arrhythmia, or symptomatic
             conduction abnormality within 12 months.

          4. History of congenital QT prolongation.

          5. QT >500.

          6. Concurrent severe or uncontrolled medical disease (i.e., active systemic infection,
             diabetes, hypertension, coronary artery disease, congestive heart failure) that, in
             the opinion of the Investigator, would compromise the safety of the patient or
             compromise the ability of the patient to complete the study.

          7. Symptomatic central nervous system metastases. The patient must be stable after
             radiotherapy for ≥2 weeks and off corticosteroids for ≥1 week.

          8. Pregnant or nursing women.

          9. Hypersensitivity or intolerance to Chloroquine, Paclitaxel, Docetaxel, Abraxane,
             Ixabepilone or other Taxane like drugs.

         10. Severe renal insufficiency (CrCl <30mL/min [Cockcroft and Gault]).

         11. History of gastrointestinal bleeding, ulceration, or perforation.

         12. Concurrent use of potent CYP3A4 inhibitors, such as ketoconazole,
             itraconazole,clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir,
             telithromycin, and voriconazole.

         13. Concurrent use of potent CYP3A4 inducers, such as dexamethasone, phenytoin,
             carbamazepine, rifampin, rifabutin, rifapentine, phenobarbitol, and St. John's wort.