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Phase II Trial of RAD001 Plus Carboplatin in Patients With Triple-Negative Metastatic Breast Cancer

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Phase II Trial of RAD001 Plus Carboplatin in Patients With Triple-Negative Metastatic Breast Cancer

This study is an open label phase II trial of carboplatin and RAD001 in women with
triple-negative breast cancer. Carboplatin will be given as an IV infusion every three
weeks. RAD001 will be given as a 5 mg pill daily with a run in of 3 patients. If there is
a dose limiting toxicity (any toxicity requiring dose modification or interruption) among
the first 3 patients, that number will be increased to 6 patients. If the 5 mg dose is
found to be tolerable among the first 3 patients, the RAD001 dose will be increased to a 10
mg pill daily. In the unexpected case of 2 or more DLT's at 5 mg/day or 1 or more DLT's in
the additional 3 patients, further dosing will be reviewed by the PI in conjunction with the
NYU DSMC. Patients will be assessed for response every two cycles with either PET/CT or CT
of the chest, abdomen, and pelvis and a bone scan. In addition patients will be followed
with serial CEA and CA 27-29 levels. The patients will continue on the protocol until there
is progression of disease or unacceptable toxicity.

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 negative)

- Age >= 18 years

- WHO performance status <= 2

- Adequate bone marrow function as shown by: ANC ≥ 1.5 x 10E9/L, Platelets ≥ 100 x
10E9/L, Hb >9 g/dL

- Adequate liver function as shown by:

1. serum bilirubin ≤ 1.5 x ULN

2. INR: Patients not on warfarin INR ≤1.5; Patients on warfarin INR ≤3; Patient on
stable dose of LMW heparin for >2 weeks at time of treatment is allowed.

3. ALT and AST ≤ 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 DLCO above 50% of the normal
predicted value of PFT)

- 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:

- 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 88% 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 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Best overall response rate (CR,PR,and SD that lasts more than 6 months)

Outcome Description:

Assessed every 2 cycles of treatment (6 weeks). The time is the estimated total time for all patients. The patients will continue on the protocol until there is progression of disease or unacceptable toxicity.

Outcome Time Frame:

up to 3 years

Safety Issue:


Principal Investigator

Amy Tiersten, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

New York University School of Medicine


United States: Institutional Review Board

Study ID:

NYU 09-0060



Start Date:

June 2010

Completion Date:

December 2013

Related Keywords:

  • Breast Cancer
  • metastatic
  • breast
  • cancer
  • Breast Neoplasms



NYU Clinical Cancer Center New York, New York  10016