RAD001 Plus Carboplatin in Breast Cancer Patients
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: RAD001; Carboplatin
Intervention MeSH terms: Carboplatin; Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: metastatic; breast; cancer

Summary:

      This study investigates the effectiveness of combination of carboplatin and investigational
      agent RAD001 in triple-negative breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Women with metastatic breast cancer (measurable or evaluable including bone metastases
             only)

          -  Histologically confirmed triple negative breast cancer (estrogen receptor (ER)< 10%,
             progesterone receptor (PR) < 10 %, Her2neu IHC 0 or 1 or FISH negative)

          -  Age >= 18 years

          -  World Health Organization performance status <= 2

          -  Adequate bone marrow function as shown by: absolute neutrophil count ≥ 1.5 x 10^9/L,
             Platelets ≥ 100 x 10^9/L, Hb >9 g/dL

          -  Adequate liver function as shown by:

               1. serum bilirubin ≤ 1.5 x upper limit of normal (ULN)

               2. 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.

               3. 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 <90%, spirometry and diffusion capacity of lung for
             carbon monoxide (DLCO) above 50% of the normal predicted value of pulmonary function
             tests)

          -  Negative serum pregnancy test within 7 days prior to starting treatment

        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
             RAD001. Topical or inhaled corticosteroids are allowed.

          -  Patients should not receive immunization with attenuated live vaccines within one week
             of study entry or during study period

          -  Uncontrolled brain or leptomeningeal metastases, including patients who continue to
             require glucocorticoids for brain or 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:

               1. Symptomatic congestive heart failure of New York heart Association Class III or
                  IV

               2. 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

               3. severely impaired lung function as defined as spirometry and DLCO that is 50% of
                  the normal predicted value and/or 02 saturation that is 88% or less at rest on
                  room air

               4. uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN

               5. active (acute or chronic) or uncontrolled severe infections

               6. 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