RAD001 Plus Carboplatin in Breast Cancer Patients

Inclusion Criteria

• Women with metastatic breast cancer (measurable or evaluable including bone metastases only)
• Histologically confirmed triple negative breast cancer (estrogen receptor (ER) = 18 years
• World Health Organization performance status 9 g/dL
• Adequate liver function as shown by:
• serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
• international normalized ratio (INR): Patients not on warfarin INR ≤1.5; Patients on warfarin INR ≤3; Patient on stable dose of low molecular weight heparin for >2 weeks at time of treatment is allowed.
• alanine aminotransferase and aspartate aminotransferase ≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases)
• Adequate renal function: serum creatinine ≤ 1.5 x ULN
• Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.
• Signed informed consent
• Patients may have had 0-3 prior regimens for metastatic disease and prior bevacizumab (avastin) is allowed.
• A baseline lung CT (or PET/CT)
• O2 sat >= 90% in room air (if 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 polymerase chain reaction 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.
• A known history of HIV seropositivity
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
• Patients with an active, bleeding diathesis
• 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 RAD001)
• Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).
• Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients
• History of noncompliance to medical regimens
• Patients unwilling to or unable to comply with the protocol
• Ongoing alcohol or drug addiction