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Open Label Randomized Clinical Trial of Standard Neoadjuvant Chemotherapy (Paclitaxel Followed by FEC) Versus the Combination of Paclitaxel and RAD001 Followed by FEC in Women With Triple Receptor-Negative Breast Cancer (CRAD001C24101)


Phase 2
18 Years
N/A
Not Enrolling
Female
Breast Cancer

Thank you

Trial Information

Open Label Randomized Clinical Trial of Standard Neoadjuvant Chemotherapy (Paclitaxel Followed by FEC) Versus the Combination of Paclitaxel and RAD001 Followed by FEC in Women With Triple Receptor-Negative Breast Cancer (CRAD001C24101)


RAD001 is a new drug that was designed to block proteins that are important in the
development and growth of cancer. It may also stop the growth of new blood vessels that
help tumor growth, resulting in cell death.

Before you can start treatment on this study, you will have "screening tests." These tests
will help the doctor decide if you are eligible to take part in this study. You will have a
complete physical exam. Blood (about 6 tablespoons) will be drawn for routine tests and to
test for the amount of fat in the blood. You will have a chest x-ray, bone scan and a 2-D
echocardiogram (a test to evaluate the pumping function of the heart). You will have a
computed tomography (CT) scan of the chest and abdomen (stomach area). Women who are able
to have children must have a negative blood (about 1 tablespoon) pregnancy test.

You will have a mammogram and an ultrasound of the breast and armpit to record tumor size.
As part of this study, you will have a fine needle biopsy of the breast tumor to test for
the signaling pathway. You will receive a separate consent form for the mammogram,
ultrasound, and biopsy and these procedures will be discussed with you in more detail. The
fine needle biopsy is a procedure that would not be performed if you were not on this study.

If you are found to be eligible to take part in this study, you will be randomly assigned
(as in the toss of a coin) to one of two treatment groups. You will have an equal chance of
being assigned to either group.

If you are assigned to Group 1, you will receive paclitaxel once a week through a needle in
your vein over 1 hour. You will have a total of 12 treatments. Before each treatment, you
may also receive drugs to help prevent or reduce your risk of side effects from paclitaxel.

If you are assigned to Group 2, you will receive paclitaxel and RAD001. You will receive
paclitaxel once a week through a needle in your vein over 1 hour. You will have a total of
12 treatments. Before each treatment, you may also receive drugs to help prevent or reduce
your risk of side effects from paclitaxel. You will take RAD001, by mouth, on each day you
receive paclitaxel. You should take RAD001 on an empty stomach or after a light meal.
Pills will not be taken out of their package until the staff is ready for you to take them,
since they can be damaged by light or humidity.

Participants in both groups will have blood (about 2 tablespoons) drawn for routine tests
before each weekly dose of chemotherapy.

You will have a second fine needle biopsy 2 days after starting treatment. This will be
done to check to see if the signaling pathway has been affected.

After your 12 weeks of treatment with paclitaxel or paclitaxel and RAD001, you will have an
ultrasound and if tumor is visible, a fine needle biopsy to check to see if the signaling
pathway has been affected.

After the 12 week treatment with either paclitaxel or paclitaxel and RAD001, you will begin
treatment with 5-fluorouracil, epirubicin, and cyclophosphamide. This drug combination is
called FEC. You will receive FEC through needle in your vein (over 1 hour) once every 3
weeks. You will have 4 treatments (12 weeks total). Before each treatment, you may also
receive drugs to help prevent or reduce your risk of side effects from FEC.

Once you have finished treatment with FEC, you will have a mammogram and ultrasound to check
the status of the disease. This mammogram and ultrasound will also be used by the doctor to
decide whether to remove all or part of the breast and/or nearby lymph nodes during surgery.

You will then have surgery to remove all or part of the breast that has the tumor. If there
are signs that the lymph nodes in the armpit contain cancer, these lymph nodes will also be
removed. You will receive a separate consent form for these procedures and your doctor will
discuss them in more detail. If available, a portion of left over tumor tissue will be
collected to check to see if the signaling pathway has been affected.

You will be considered "off study" once you have had surgery. You will be taken off study
early if the disease gets worse or intolerable side effects occur.

This is an investigational study. Paclitaxel, 5-fluorouracil, cyclophosphamide, and
epirubicin are all FDA approved and commercially available. RAD001 is not FDA approved or
commercially available. It has been authorized for use in research only. Up to 50 patients
will take part in this study. All will be enrolled at M. D. Anderson.


Inclusion Criteria:



1. Patients with histologic confirmation of invasive ER/PR and HER2/neu-negative breast
carcinoma. Immunohistochemistry (IHC) must be used for ER/PR evaluation and IHC or
FISH for determination of HER2/neu. ER/PR will be considered negative if equal or
lower than 5% IHC staining and HER2/neu will be considered negative if IHC of 0% or
negative FISH.

2. Patients must have intact primary tumors.

3. Age equal or greater than 18 years

4. Patients should have stage IIA (T1N1) to IIIC non inflammatory breast cancer.

5. Patients with bilateral breast cancers are eligible.

6. Patients should have a Karnofsky performance scale of =/> 70%.

7. Patients must have clinically measurable disease to be treated in the neoadjuvant
setting. This includes patients with a non-palpable primary tumor who have
histologically proven lymph node involvement that is clinically palpable and
measurable by ultrasound.

8. Patients should have adequate bone marrow function, as defined by peripheral
granulocyte count of >/= 1500/mm3, and a platelet count >/= 100000/ mm3.

9. Patients must have adequate liver function with a bilirubin within normal laboratory
values. Alkaline phosphatase and transaminases (ALT and AST) may be up to 1.5 x upper
limit of normal (ULN) of the institution.

10. Patients should have adequate renal function with creatinine levels 2.0 mg/dL or
lower

11. Patients should have a normal left ventricular ejection fraction of =/> 50%.

12. Negative serum pregnancy test for a woman of childbearing potential.

13. Women of childbearing potential (WOCBP) must use a reliable and appropriate
contraceptive method during the study and 6 months after chemotherapy is completed.
WOCBP are women who are not menopausal for 12 months or had no previous surgical
sterilization.

14. Patients must agree to have study biopsies.

15. Patients must sign an informed consent indicating that they are aware of the
investigational nature of the study, in keeping with institutional policy.

16. Hemoglobin 9.0 gm/dL or higher

Exclusion Criteria:

1. Patients whose tumors express ER, PR or HER2/neu gene amplification.

2. Patients with a history of other invasive malignancies diagnosed and treated within
the previous 5 years, except non-melanoma skin cancer and non-invasive cervical
cancer

3. Patients with an organ allograft or other history of immune compromise

4. Prior exposure to mTOR inhibitors

5. Hypersensitivity to rapamycin or other similar compounds

6. Prior treatment with any investigational drug within the preceding 4 weeks

7. Chronic treatment with systemic steroids or another immunosuppressive agent

8. A known history of HIV seropositivity

9. 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)

10. Patients with an active, bleeding diathesis or on oral anti-vitamin K medication
(except low dose coumadin defined as 1 mg a day).

11. Other concurrent severe and/or uncontrolled medical disease which could compromise
participation in the study (i.e., uncontrolled diabetes, uncontrolled hypertension,
severe infection, severe malnutrition, unstable angina, or congestive heart failure -
New York Heart Association Class III or IV, ventricular arrhythmias, active ischemic
heart disease, myocardial infarction within six months, chronic liver or renal
disease, active upper GI tract ulceration)

12. Patients with a pre-existing peripheral neuropathy > grade 1

13. Patients taking medications metabolized by the CYP3A4 subfamily will not be included
in this study.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number Participants with Inhibition of PI3K/PTEN/AKT Pathway

Outcome Description:

Baseline (start of treatment) and at 48 hours after start of treatment

Outcome Time Frame:

48 hours after start of treatment

Safety Issue:

No

Principal Investigator

Ana Gonzalez-Angulo, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

2006-0790

NCT ID:

NCT00499603

Start Date:

July 2007

Completion Date:

April 2012

Related Keywords:

  • Breast Cancer
  • Breast Cancer
  • ER negative
  • PR negative
  • HER2neu negative
  • Tumor Triple Negative Receptors
  • Paclitaxel
  • Taxol
  • RAD001
  • FEC
  • 5-Fluorouracil
  • 5-FU
  • Adrucil
  • Efudex
  • Epirubicin
  • Cyclophosphamide
  • Breast Neoplasms

Name

Location

U.T. M.D. Anderson Cancer CenterHouston, Texas  77030