Comparison of Single-Agent Carboplatin vs the Combination of Carboplatin and Everolimus for the Treatment of Advanced Triple-Negative Breast Cancer

Inclusion Criteria:

- Women with metastatic breast cancer (measurable or evaluable including bone metastases
only)

- Histologically confirmed triple negative breast cancer (ER< 10%, PR < 10%, Her2neu IHC
0 or 1 or FISH/ISH negative)

- Age ≥ 18 years

- WHO performance status ≤ 2

- Adequate bone marrow function as shown by: ANC ≥ 1.5 x 10^9/L, Platelets ≥ 75 x
10^9/L, Hb >9 g/dL

- Adequate liver function as shown by:

- serum bilirubin ≤ 1.5 x ULN

- ALT and AST ≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases)

- Adequate renal function: serum creatinine ≤ 1.5 x ULN

- Signed informed consent

- Patients may have had up to 3 prior regimens for metastatic disease

- A baseline CT chest/abdomen/pelvis and bone scan or PET/CT

- Negative serum pregnancy test within 7 days prior to starting treatment

- Stable brain metastases allowed (> 2 weeks, clinically-stable post treatment with
surgery+/-radiation or radiation alone and off steroids)

- Prior carboplatin allowed provided greater than 12 mos have elapsed since last dose of
carboplatin

Exclusion Criteria:

- Patients currently receiving anticancer therapies or who have received anticancer
therapies within 2 weeks of the start of study drug (including chemotherapy, radiation
therapy, and biologics)

- Patients, who have had a major surgery or significant traumatic injury within 4 weeks
of start of study drug, patients who have not recovered from the side effects of any
major surgery (defined as requiring general anesthesia) or patients that may require
major surgery during the course of the study

- Prior treatment with any investigational drug within the preceding 2 weeks

- Patients receiving chronic, systemic treatment with corticosteroids or another
immunosuppressive agent, except corticosteroids with a daily dosage equivalent to
prednisone ≤ 20 mg. However, patients receiving corticosteroids must have been on a
stable dosage regimen for a minimum of 4 weeks prior to the first treatment with
Everolimus. Topical or inhaled corticosteroids are allowed.

- Co-administration with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole,
ritonavir) or P-glycoprotein (PgP) is prohibited. Co-administration with moderate
CYP3A4 inhibitors (e.g., erythromycin, fluconazole) or PgP inhibitors may be used with
caution and everolimus dosing must be discussed with PI at the time of enrollment. For
a current table of Substrates, Inhibitors and Inducers please access the following
website:http://www.fda.gov/Drugs/DevelopmentApprovalProcess/"

- Patients who have received live attenuated vaccines within 1 week of start of
Everolimus and during the study. Patient should also avoid close contact with others
who have received live attenuated vaccines. Examples of live attenuated vaccines
include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever,
varicella and TY21a typhoid vaccines

- Uncontrolled brain metastases

- Leptomeningeal metastases

- Other malignancies within the past 3 years except for adequately treated carcinoma of
the cervix or basal or squamous cell carcinomas of the skin.

- Patients who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation in the study such as:

- Symptomatic congestive heart failure of New York heart Association Class III or
IV

- unstable angina pectoris, symptomatic congestive heart failure, myocardial
infarction within 6 months of start of study drug, serious uncontrolled cardiac
arrhythmia or any other clinically significant cardiac disease

- severely impaired lung function as defined as spirometry and DLCO that is 50% of
the normal predicted value and/or 02 saturation that is 89% or less at rest on
room air

- uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN

- active (acute or chronic) or uncontrolled severe infections

- liver disease such as cirrhosis, chronic active hepatitis or chronic persistent
hepatitis Note: A detailed assessment of Hepatitis B/C medical history and risk
factors must be done at screening for all patients. HBV DNA and HCV RNA PCR
testing are required at screening for all patients with a positive medical
history based on risk factors and/or confirmation of prior HBV/HCV infection. See
Appendix I (Hep Screening Form)

- A known history of HIV seropositivity

- Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of Everolimus (e.g., ulcerative disease,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel
resection)

- Patients with an active, bleeding diathesis

- Patients who have received prior treatment with an mTOR inhibitor (sirolimus,
temsirolimus, everolimus).

- Patients with a known hypersensitivity to Everolimus or other rapamycins (sirolimus,
temsirolimus) or to its excipients

- Patients with a known hypersensitivity to carboplatin

- History of noncompliance to medical regimens

- Patients unwilling to or unable to comply with the protocol

- Ongoing alcohol or drug addiction

- Female patients who are pregnant or breast feeding, or adults of reproductive
potential who are not using effective birth control methods. If barrier contraceptives
are being used, these must be continued throughout the trial by both sexes. Hormonal
contraceptives are not acceptable as a sole method of contraception. (Women of
childbearing potential must have a negative urine or serum pregnancy test within 7
days prior to administration of Everolimus)