The goal of this clinical research study is to learn if receiving 4 cycles of experimental
chemotherapy before surgery can help to shrink the size of tumors in the breast and/or lymph
nodes before they are removed through surgery. The safety of this combination will also be
Study Drug Administration:
If you are found eligible to take part in this study, you will have 4 cycles of chemotherapy
before surgery. Each cycle is 21 days.
On Day 1 of each cycle, you will receive liposomal doxorubicin by vein over about 3 hours,
and bevacizumab by vein over about 90 minutes (about 4½ hours total). You will also be given
a 21-day supply of everolimus which you will take by mouth at about the same time every day
during the cycle.
To reduce the possibility of side effects from surgery, you will not receive bevacizumab
during the 4th cycle.
Do not skip any doses unless your study doctor tells you to do so. If you throw up after
taking everolimus, you should NOT take another tablet that day. Let your study doctor know
that you vomited. If you forget to take everolimus one day, do not take any extra doses the
next day. Call your study doctor and ask for advice.
If you have side effects, the study doctor may decide to lower your study drug dose or have
you stop taking the drug. If this happens, the study doctor and staff will let you know when
it is safe to restart the study drug later at the same or a lower dose. The study doctor
will discuss this with you. If study drug is stopped for a while, you may have extra clinic
visits for safety tests.
On Day 1 of each cycle:
- You will have a physical exam.
- Blood (about 2 teaspoons) and urine will be collected for routine tests.
After you have received 4 cycles of chemotherapy, or at any time that the disease appears to
get worse, you will have imaging scans similar to the ones you had at screening to check the
status of the disease. If the disease gets worse, you may come off study and might have
either more chemotherapy or surgery.
You may then have surgery to remove the disease. You will be given a surgery consent form
that describes the procedure and its risks.
Length of Treatment:
You may receive up to 4 cycles of chemotherapy. You will no longer be able to take the study
drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to
follow study directions.
Your participation on the study will be over after the follow-up visit.
About 2-3 weeks after surgery, you will have a follow-up visit in which you are asked about
how you are doing. The following test will be preformed:
You will have a physical exam. Blood (about 2 teaspoons) and urine will be collected for
routine tests. If your doctor thinks it is needed, you will have an ultrasound, MRI, or CT
scan of your chest to check the status of the disease.
This is an investigational study. Liposomal doxorubicin is FDA approved and commercially
available for the treatment of breast cancer. Bevacizumab and everolimus have both been FDA
approved for other conditions and types of cancer. However, neither bevacizumab nor
everolimus are FDA-approved for triple-negative breast cancer. They are currently being used
for research purposes only in this setting as triple-negative breast cancer treatment before
The study doctor can explain how these study drugs are designed to work.
Up to 37 participants will be enrolled in this study. All will take part at MD Anderson.
1. Age >/= 18 years.
2. ECOG performance status of 0 or 1.
3. Confirmed invasive triple-negative breast cancer defined as ER<10%; PR<10% by
immunohistochemistry (IHC) and HER2 0-1+ (by IHC), or 2+ (FISH <2, gene copy number
4. Primary tumor sample collected before NACT started and
5. Undergone molecular testing for integral biomarkers including immunohistochemical
staining for vimentin.
6. Received at least one dose of an anthracycline-based NACT. Patients are eligible if
therapy was discontinued due to disease progression or therapy intolerance.
7. At least 1.0 cm of measurable residual disease after neoadjuvant anthracycline-based
8. Baseline MUGA or echocardiogram showing LVEF >/=50% at least 6 weeks prior to
initiation of NACT.
9. Adequate bone marrow function as shown by: ANC >/=1.5 x 10^9/L, Platelets >/=100 x
10^9/L, Hb >9 g/dL;
10. Adequate liver function as shown by: Total serum bilirubin </=2.0 mg/dL, ALT and AST
</=2.5x ULN (</=5x ULN in patients with liver metastases), INR </=2;
11. Adequate renal function as shown by: Serum creatinine </=1.5x ULN;
12. Fasting serum cholesterol </=300 mg/dL OR </=7.75 mmol/L, AND fasting triglycerides
</=2.5x 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;
13. Signed informed consent obtained prior to any screening procedures.
1. Pregnant or lactating woman.
2. Presence of metastatic disease.
3. Prior therapy with bevacizumab, liposomal doxorubicin, or everolimus.
4. Prior radiation therapy of the primary breast carcinoma or axillary lymph nodes.
5. Patients who have a history of another primary malignancy, with the exceptions of:
non-melanoma skin cancer, and carcinoma in situ of the cervix, uterus, or breast from
which the patient has been disease free for </= 3 years.
6. Prior cumulative dose of doxorubicin of greater than 360 mg/m2 or epirubicin of
greater than 640 mg/m2.
7. Any serious medical illness, other than treated by this study, which would limit
survival to less than 1 month or psychiatric illness which would limit informed
8. Patients with history of serious cardiac events defined as: New York Heart
Association Class 3 or 4 heart failure, history of myocardial infarction, Unstable
angina, or CVA within 6 months of protocol registration. History of PR prolongation
or AV block.
9. Known intolerance or hypersensitivity to rapamycin analogs (e.g. sirolimus,
10. Known impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of oral Everolimus;
11. Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy.
Patients with a known history of impaired fasting glucose or diabetes mellitus (DM)
may be included, however blood glucose and antidiabetic treatment must be monitored
closely throughout the trial and adjusted as necessary;
12. Patients who have any severe and/or uncontrolled medical conditions such as: a.
serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac
disease b. active (acute or chronic) or uncontrolled severe infection, liver disease
such as cirrhosis, decompensated liver disease, and active and chronic hepatitis
(i.e. quantifiable HBV-DNA and/or positive HBsAg, quantifiable HCV-RNA), c. known
severely impaired lung function (spirometry and DLCO 50% or less of normal and O2
saturation 88% or less at rest on room air), d. active, bleeding diathesis; e.
Moderate or severe hepatic impairment (Child-Pugh B or C)
13. Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or
inhaled corticosteroids are allowed;
14. Known history of HIV seropositivity;
15. Patients who have received live attenuated vaccines within 1 week of start of
Everolimus and during the study. Patient should also avoid close contact with others
who have received live attenuated vaccines. Examples of live attenuated vaccines
include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever,
varicella and TY21a typhoid vaccines;
16. Patients with a history of non-compliance to medical regimens or who are considered
potentially unreliable or will not be able to complete the entire study;
17. Patients who are currently part of or have participated in any clinical investigation
with an investigational drug within 1 month prior to dosing;
18. Women of child-bearing potential (WOCBP), defined as all women physiologically
capable of becoming pregnant, must use highly effective methods of contraception
during the study and 8 weeks after. Highly effective contraception methods include
combination of any two of those listed in the protocol.
19. Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate
contraception, during the study and for 8 weeks after the end of treatment.