Chloroquine With Taxane Chemotherapy for Advanced or Metastatic Breast Cancer After Anthracycline Failure (CAT)

The purpose of this study is to determine the anti-tumor activity of the combination of
Chloroquine combined with a Taxane or Taxane-like chemo agents(Paclitaxel, Docetaxel,
Abraxane, Ixabepilone).

The laboratories have developed robust preclinical models utilizing both in vitro systems
such as the mammosphere (MS) culture and in vivo systems such as human breast cancer
xenografts allowing the investigators to identify agents which selectively target TICs, as
single agents or in combination. These models are critical since tumor initiating cells
(TICs) comprise only a small percentage of the tumor bulk, so that clinical tumor regression
may not be observed with inhibitors that selectively target TIC self-renewal alone.
Nonetheless, these agents in combination with conventional therapy may effectively kill both
actively cycling or fully differentiated cells and the TIC subpopulation, leading to long
term remission and eradication of cancer cells.

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.