Study of the Efficacy of Chloroquine in the Treatment of Ductal Carcinoma in Situ (The PINC Trial)

The purpose of this study is to test the hypothesis that inhibiting the autophagy pathway in
DCIS will reduce the capacity of DCIS to survive and invade. The study will examine the
safety and effectiveness of neoadjuvant chloroquine administration for a one month period to
patients with low, intermediate grade, or high grade DCIS. We will evaluate whether this
treatment will reduce the capacity of DCIS neoplastic cells, existing within the duct, to
survive, induce lesion regression, and kill the invasive DCIS progenitor cells.

Inclusion Criteria:

- Patients must have a tissue diagnosis of low, intermediate or high grade ductal
carcinoma in situ or ductal carcinoma in situ with microinvasion.

- Patients with ductal carcinoma in situ undergoing either lumpectomy/radiation or
mastectomy.

- Patients must be female at least 18 years of age.

- Patients must have a signed tissue acquisition consent and have at minimum, adequate
samples of primary fresh tissue or blood available for use in this study.

- No history of a previous invasive cancer in the last five years with the exception of
minimally invasive non-melanoma skin cancer.

- Normal liver function based on Liver Function Tests (Total Bilirubin and AST <1.5 X
Upper Limit of Normal).

- Normal WBC (3.5-10.8 x 103µL), PLT (140-400 x 103µL), and HCT (37-52%)

- Potassium within the normal range of 3.5-5.3 mEq/L

- Adequate renal sufficiency (serum creatinine <1.5 mg/dL).

- ECOG performance status 0-2.

- Are able to swallow and retain oral medication.

- No underlying ocular/retinal pathology.

- No medically documented preexisting auditory damage.

- Subjects should be willing to abstain from use of hormonal therapies (e.g. hormone
replacement therapy, oral contraceptive pills, hormone-containing IUDs, and E-string)
and chronic NSAID's for the duration of the study (chronic use of NSAID's is defined
as a frequency >3 times/week for more than two weeks per year and includes low dose
aspirin).

- Subjects with child-bearing potential must agree to use adequate contraception (total
abstinence (no sexual intercourse), use of condom with spermicide or sterilization
surgery, including tubal ligation (tubes tied) or hysterectomy (removal of the uterus
or womb)) prior to study entry and for the duration of study treatment phase. Should
a woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her study physician immediately.

If a subject is of child-bearing potential (women are considered not of child-bearing
potential if they are at least one year postmenopausal and/or surgically sterile), she
must have a documented negative serum or urine pregnancy test before starting treatment.

Exclusion Criteria:

- Patients with a prior history of chemotherapy, hormonal ablation therapy and/or
radiation therapy.

- History of other invasive cancer in the previous 5 years other than minimally
invasive non-melanoma skin cancer.

- Patient desires not to participate in the study.

- Inability to consent.

- Current or recent pregnancy (within 12 months),

- Current use of hormone-containing forms of birth control such as implants (i.e.
Norplants, or injectables ( i.e. depo-provera)

- Currently lactating.

- Patients with history of renal or hepatic insufficiency.

- Current diagnosis for depression, including treatment with an SSRI.

- History of prior treatment with chloroquine for malaria within past 24 months.

- History of allergic reactions to quinalones or chloroquine.

- Active diagnosis of psoriasis or currently receiving treatment for psoriasis.

- History of porphyria.

- History of known Glucose-6-Phosphate Dehydrogenase (G-6-PD) deficiency.

- Alcoholism or hepatic disease.

- History of epilepsy or seizures in the past 20 years.

- History of deep vein thrombosis or pulmonary embolism.

- History of HIV disease and/or treatment with anti-HIV agents.

- Receiving concurrent treatment with prohibited medications (refer to Table 1 for
details on prohibited medications); Examples include: ampicillin, antacids,
cimetidine, cyclosporine, kaolin, magnesium trisilicate, coumarin-type
anticoagulants, macrolide antibiotics (e.g., clarithromycin, isoniazid, and
erythromycin), anti-HIV agents (e.g., ritonavir and delavirdine), antidepressants
(e.g. fluoxetine and fluvoxamine), calcium channel blockers (e.g. verapamil and
diltiazem), steroids and their modulators (e.g., gestodene, raloxifene, and
mifepristone), and several herbal and dietary components (e.g. bergamottin and
glabridin).

- Used an investigational drug within 30 days or 5 half-lives, whichever is longer,
preceding the first dose of study medication.