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A Phase II Trial of RAD001 in Triple Negative Metastatic Breast Cancer

Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

A Phase II Trial of RAD001 in Triple Negative Metastatic Breast Cancer

RAD001 is an orally administered cell cycle inhibitor with antitumor activity. RAD001, like
Rapamycin, binds with high affinity to an intracellular immunophilin, FKBP12 and this
complex specifically interacts with the mammalian target of rapamycin (mTOR) protein kinase,
inhibiting downstream events such as the initiation of mRNA translation. RAD001 inhibits the
growth of a wide range of histologically diverse tumor cells. RAD001 is being developed as a
cytostatic agent to delay the time to tumor recurrence/progression or to increase survival
in patients with various malignancies. The compound has good tolerability, a partially
discovered mechanism of action. RAD001 has the ability to arrest cells in the G1 phase, and
the ability to induce apoptosis. RAD001 is being investigated as an anticancer agent based
on its potential to act directly on the tumor cells by inhibiting tumor cell growth and
proliferation through possible inhibition of the PI3/AKT/MTOR pathway.

RAD001 was shown to have activity in human tumor cell lines originating from lung, breast,
prostate, colon, kidney, melanoma and glioblastoma. RAD001 was also shown to have activity
in human pancreatic neuroendocrine cells, where induction of apoptosis was reported, as well
as in acute myeloid leukemia cells, adult T-cell leukemia cells, diffuse large B cell
lymphoma cells, pancreatic tumor cells, ovarian cancer cells, and hepatocellular carcinoma

Inclusion Criteria:

- Eastern Cooperative Group (ECOG) performance status ≤ 2

- Age ≥ 18 years

- At least one measurable site of disease according to RECIST criteria that has not
been previously irradiated. If the patient has had previous radiation to the marker
lesion(s), there must be evidence of disease progression since the radiation

- Adequate bone marrow function as shown by: Absolute Neutophil Count (ANC) ≥ 1.5 x
109/L, Platelets (PLT)≥ 100 x 109/L, Hemoglobin (HGB) ≥9 g/dL

- Adequate liver function as shown by:Serum bilirubin ≤ 1.5 x upper limits of normal
(ULN), Prothrombin Time (INR) ≤ 1.3 (or ≤ 3 on anticoagulants), Liver function teats
≤ 2.5x ULN (≤ 5x ULN in patients with liver metastases)

- Adequate renal function: serum creatinine ≤ 1.5 x ULN

- Controlled diabetes as defined by fasting serum glucose ≤1.5 x ULN

- Fasting serum cholesterol ≤300 mg/dL or ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5
x ULN.

Exclusion Criteria:

- Currently receiving anticancer therapies or who have received anticancer therapies
within 4 weeks of the start of study drug (including chemotherapy, antibody based
therapy, etc.)

- Palliative radiation therapy only allowed to localized areas (ie: painful rib
lesion), at the discretion of the PI and treating radiation oncologist

- Major surgery/significant traumatic injury within 4 weeks of start of study drug.

- Not recovered from the side effects of any major surgery (defined as requiring
general anesthesia) to Grade I or patients that may require major surgery during the
course of the study.

- Prior treatment with any investigational drug within the preceding 4 weeks

- Receiving chronic immunosuppressive agents, except corticosteroids with a daily
dosage equivalent to prednisone ≤ 20 milligrams (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

- May 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 and basal or squamous cell carcinomas of the skin.

- Severe and/or uncontrolled medical conditions or other conditions that could affect
their participation in the study such as: Congestive heart failure: New York Heart
Association Class III/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.

- Impaired lung function (PFT screen at baseline) 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. Glucose
control should be achieved before starting a patient on RAD001.

- Active (acute or chronic) or uncontrolled severe infections

- Liver disease(cirrhosis, chronic active hepatitis or chronic persistent hepatitis)

- Known history of Human Immunodeficiency Virus (HIV) seropositivity

- Impairment of gastrointestinal function/disease that may significantly alter the
absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting,
diarrhea, malabsorption syndrome or small bowel resection)

- Active, bleeding diathesis

- Female patients who are pregnant or breast feeding, or adults of reproductive
potential who are not using effective birth control methods.

- Prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).

- Known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus,
temsirolimus) or to its excipients

Type of Study:


Study Design:

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

Outcome Measure:

Time to Progression(TTP)

Outcome Description:

Progression is defined by RESIST criteria as any new lesion or the sum of target lesions increasing by 20% over baseline

Outcome Time Frame:

Each patient assessed at 8 weeks from start of study drug

Safety Issue:


Principal Investigator

Allan Lipton, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Penn State Milton S. Hershey


United States: Food and Drug Administration

Study ID:




Start Date:

April 2009

Completion Date:

February 2011

Related Keywords:

  • Breast Cancer
  • Breast cancer
  • metastatic breast
  • triple negative
  • ER/PR negative
  • Her2 Neu negative
  • Breast Neoplasms



Penn State Milton S. Hershey Medical Center Hershey, Pennsylvania  17033