A Phase II Neo-Adjuvant Study of Cisplatin, Paclitaxel With or Without RAD001 in Patients With Triple-negative Locally Advanced Breast Cancer.

Inclusion Criteria

Eligibility criteria

-Maximum number of patients will include two-thirds of the patients in Arm 1 and one-third
of the patients for Arm 2 (total of 145 patients). Estimated time for accrual with ~ 3
patients/month would be ~ 3.5 years.

Inclusion criteria:

- Patients must provide informed written consent.

- Patient must be ≥ 18 years of age.

- ECOG performance status 0-1.

- Clinical stage II or stage III triple-negative (ER and/or PR no staining or weak
staining in less than or equal to 10% cells by immunohistochemistry [IHC] and
HER2-negative by Herceptest [0, 1+] or FISH) invasive mammary carcinoma, confirmed by
histological analysis.

- Patients who have measurable* residual tumor at the primary site

*Measurable disease: any mass that can be reproducibly measured by physical
examination, mammogram, and/or ultrasound and can be accurately measured in at least
one dimension (longest diameter to be recorded) as 10 mm (1 cm), either in the breast
or axillary lymph nodes.

- Available core biopsies from the time of diagnosis. Fresh tissue must be obtainable
at baseline or fresh tissue biopsy prior to treatment initiation.

- Patients who will undergo surgical treatment with either segmental resection or total
mastectomy.

- Patients must have adequate hematologic, hepatic, and renal function. All tests must
be obtained less than 4 weeks from study entry. This includes:

- ANC >/=1500/mm3

- Platelet count >/=100,000/mm3

- Creatinine
- Bilirubin, SGOT, SGPT
* for patients with Gilbert‟s syndrome, direct bilirubin will be measured instead of
total bilirubin.

- The patient must have not had anyprior chemotherapy for primary breast cancer.

- Patients with a prior history of contra-lateral breast cancer are eligible if they
have no evidence of recurrence of their initial primary breast cancer within the last
5 years.

- Able to swallow and retain oral medication.

- Four days prior to biopsy procedures patients must be off medications that could
increase risk of bleeding (i.e. ASA, NSAIDS, Coumadin, heparin products)

- Potential subjects must complete all screening assessments as outlined in the
protocol.

- The pre-menopausal patient of childbearing potential must have had a negative
pregnancy test and agreed to use birth control methods while participating in the
study. Note: Women of childbearing potential and their male counterparts should use a
barrier method of contraception during and for 3 months following protocol therapy.

Ineligibility Criteria

Exclusion Criteria:

- Locally recurrent breast cancer.

- Pregnant or lactating women.

- Evidence of distant metastatic disease (i.e. lung, liver, bone, brain, etc.)

- Use of CYP3A4 modifiers (Appendix A)

- Serious medical illness that in the judgment of the treating physician places the
patient at high risk of operative mortality.

- Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
resection of the stomach or small bowel.

- History of other malignancy. Subjects who have been disease-free for 5 years, or
subjects with a history of completely resected non-melanoma skin cancer or
successfully treated in situ carcinomas are eligible.

- History of hepatitis B or hepatitis C. If patient is judged to be at risk for having
had exposure to viral B or C hepatitis (i.e. illicit IV drug use, blood transfusion
prior to 1990, body piercing, tattoos, etc.), appropriate testing should be performed
(i.e. Hepatitis B surface antigen antibody, and Hepatitis C antibody)

- Active or uncontrolled infection requiring parenteral antibiotics.

- Dementia, altered mental status, or any psychiatric condition that would prohibit the
understanding or rendering of informed consent.

- Symptomatic neuropathy (≥ grade 2).

- Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery,
immunotherapy, hormonal therapy, or any other biologic therapy) other than the ones
specified in the protocol.

- Concurrent treatment with an investigational agent.

- Used an investigational drug within 15 days or 5 half-lives, whichever is longer,
preceding the first dose of randomized therapy.