This phase IIB trial studies how well enzalutamide and paclitaxel before surgery works in
treating patients with stage I-III androgen receptor-positive triple-negative breast cancer.
Androgens can cause the growth of triple-negative breast cancer. Anti-hormone therapy, such
as enzalutamide, prevent androgen from binding to the androgen receptor, thereby decreasing
cell growth and causing tumor cell death. Drugs used in chemotherapy, such as paclitaxel,
work in different ways to stop the growth of tumor cells, either by killing the cells, by
stopping them from dividing, or by stopping them from spreading. Giving enzalutamide and
paclitaxel before surgery may make the tumor smaller and reduce the amount of normal tissue
that needs to be removed. This treatment study is part of the MD Anderson Moonshot
Phase IIB Neoadjuvant <span class="go-doc-concept go-doc-intervention">Enzalutamide</span> (ZT) Plus <span class="go-doc-concept go-doc-intervention">Taxol</span> for Androgen Receptor (<span class="go-doc-concept go-doc-biomarker">AR</span>)-Positive <span class="go-doc-concept go-doc-keyword">Triple-Negative</span> Breast Cancer (<span class="go-doc-concept go-doc-biomarker">AR</span>+ TNBC)
Brief Title: Phase IIB Neoadjuvant Enzalutamide (ZT) Plus Taxol for Androgen Receptor (AR)-Positive Triple-Negative Breast Cancer (AR+ TNBC)
Official Title: A Phase IIB Study of Neoadjuvant Enzalutamide (ZT) Regimen Therapy in Combination With Weekly Paclitaxel for Androgen Receptor (AR)-Positive Triple-Negative Breast Cancer
Clinical Trial IDs
NCT ID: NCT02689427
ORG ID: 2015-0488
||Enzalutamide + Paclitaxel
||Enzalutamide + Paclitaxel
The goal of this clinical research study is to learn if a combination of enzalutamide and
paclitaxel can help to control TNBC by shrinking the tumors in the breast and/or lymph nodes
before they are surgically removed. The safety of this treatment combination will also be
Study Drug Administration:
If participant is found eligible to take part in this study, they will take enzalutamide by
mouth every day for 12 study cycles. Each cycle is 7 days (1 week).
On Day 1 of each cycle, participant will receive paclitaxel by vein over about 2 hours.
If participant has side effects, the study doctor may decide to lower their study drug dose
level or have them stop taking the drug for a short time. If participant's dosing is
stopped, they may be able to restart the study drug later at the same dose or a lower dose.
The study doctor will discuss this with participant.
Before Day 1 of Cycle 1, participant will have an image-guided core biopsy to collect tumor
tissue. To perform an image-guided biopsy, a needle is inserted into the affected area using
imaging scans to collect cells or tissue from an organ, lymph node, or suspected tumor mass.
The doctor will use the imaging to guide the needle into the area. Up to three (3) samples
may be collected and will be used for two (2) types of tests. It will be a core biopsy that
collects a small piece of tissue.
If enough tissue can be collected, the tissue samples will be used for biomarker testing
(including genetic biomarkers). Biomarkers are found in the blood/tissue and may be related
to participant's reaction to the study drug.
On Day 1 of each cycle:
- Participant will have a physical exam.
- Blood will be drawn for CTC tests.
On Day 1 of Cycle 7, blood (about 2 teaspoons) will be drawn for CTC tests.
Any time during the 12 study cycles, participant may have imaging scans (the same ones that
were performed at Screening) to check the status of the disease, if the doctor thinks they
At the end of 12 cycles:
- Participant will have a physical exam.
- Blood (about 2 teaspoons) will be drawn for routine tests and CTC tests.
- Participant will have imaging scans of the breast and lymph nodes to check the status
of the disease.
- Participant will have an image-guided core biopsy to collect breast tissue for
biomarker testing (including genetic biomarkers). This breast tissue sample may be
collected later, during participant's surgery, rather than at the end of Cycle 12. This
will be up to the study doctor.
After 12 cycles of study drugs on this study, participant may then have surgery to remove
the tumor(s). Participant will be given a surgery consent form that describes the procedure
and its risks. If participant does not have surgery, they may still have a lymph node biopsy
or removal, based on standard care. Participant's doctor can discuss this with them.
Leftover tissue/blood from study testing will be banked at MD Anderson. Before participant's
samples can be used for research, the researchers must get approval from the Institutional
Review Board (IRB) of MD Anderson. The IRB is a committee of doctors, researchers, and
community members. The IRB is responsible for protecting study participants and making sure
all research is safe and ethical.
Participant's samples will be given a code number. No identifying information will be
directly linked to participant's samples. Only the researcher in charge of the bank will
have access to the code numbers and be able to link the samples to participant. This is to
allow medical data related to the samples to be updated as needed.
Length of Treatment:
Participant may receive up to 12 cycles of chemotherapy. Participant will no longer be able
to take the study drugs if the disease gets worse, if intolerable side effects occur, or if
they are unable to follow study directions.
Patient's participation on the study will be over after the follow-up visit.
Within 30 days (+/- 3 days) after surgery/biopsy, participant will have a follow-up visit.
During this visit, participant will be asked about how they are doing, and blood (about 2
teaspoons) will be drawn for routine tests.
This is an investigational study. Paclitaxel is FDA approved and commercially available for
the treatment of breast cancer that does not respond to chemotherapy. Enzalutamide is not
FDA-approved for breast cancer. It is currently being used for research purposes only in
breast cancer patients. The study doctor can explain how these study drugs are designed to
Up to 37 participants will be enrolled in this study. All will take part at MD Anderson.
|Enzalutamide + Paclitaxel
||Participants receive Enzalutamide by mouth every day for 12 study cycles. Each cycle is 7 days (1 week).
On Day 1 of each cycle, participants receive Paclitaxel by vein over about 2 hours.
1. Patients must be willing to sign the protocol-specific written informed consent.
2. Patients with histologically confirmed intact primary cancer that is confirmed
invasive carcinoma of the breast who have at least 1.0 cm of measurable residual
disease on imaging by either mammography, ultrasound, or breast MRI after neoadjuvant
anthracycline based chemotherapy.
3. Patients must have triple-negative breast cancer defined as ER<10%; PR<10% by
immunohistochemistry (IHC) and HER2 0-1+ by IHC or 2+, FISH non-amplified.
4. AR will be stained using CLIA-compliant assays for AR with the initial biopsy
specimen. AR- positivity is defined as >/= 1% of nuclear staining.
5. Patient's disease state must be AJCC 7th edition stage I-III.
6. Men or women must be 18 years of age or older.
7. Patients must have a performance status of </= to 1 on the ECOG performance scale.
8. A negative serum or urine pregnancy test must be done within 72 hours before the
first dose of the study medication for women of childbearing potential as per
institutional guidelines. Post-menopausal women (defines as no menses for at least 1
year) and surgically sterilized women are not required to undergo pregnancy test.
9. Men on study must use a condom if having sex with a pregnant woman.
10. Male patients and his female partner who is of childbearing potential must use 2
acceptable methods of birth control (one of which must include a condom as a barrier
method of contraception) starting at screening and continuing throughout the study
period and for 3 months after final study drug administration.
11. Patient must have adequate organ function as determined by the following laboratory
values: 1) Absolute neutrophil count >/= to 1,500 /uL 2) Platelets >/= to 100,000 /
uL 3) Hemoglobin >/= to 9 g/dL 4) Creatinine clearance >/= to 50 ml/min 5) Total
bilirubin </= to 1.5 X ULN 6) Alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) </= to 2.5 X ULN.
1. Patients must have not have received any other previous antitumor therapies other
than anthracycline-based chemotherapy for the current cancer event.
2. Female patients must not be breast-feeding at screening or planning to become
pregnant during the course of therapy.
3. Patients must not have had major surgery within 21 days before Cycle 1, Day 1.
4. Patients must not have a known history of hypersensitivity to paclitaxel that did not
resolve with pre- medication.
5. Patients must not have left ventricular ejection fraction <50% or 10% decrease from
baseline on echocardiogram after anthracycline based chemotherapy.
6. Patients must not have gastrointestinal tract disease or defect or previous history
7. Subjects must not be requiring daily corticosteroids, other than those given as
premedication for the anthracycline-based chemotherapy.
8. Patients must not have a known or suspected brain metastasis or active leptomeningeal
9. Must not have a history of seizure or any condition that may predispose to seizure
(e.g., prior cortical stroke, significant brain trauma) at any time in the past.
Also, history of loss of consciousness or transient ischemic attack within 12 months
of Day 1 visit.
10. Must not have had a myocardial infarction within 6 months before starting therapy,
symptomatic congestive heart failure (New York Heart Association > class II),
unstable angina, or unstable cardiac arrhythmia requiring medication.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both
Primary Outcome Measures
Pathologic Complete Response (pCR) of Participants with Triple Negative Breast Cancer (TNBC)
Minimal Residual Disease (RCB-I) of Participants with Triple Negative Breast Cancer (TNBC)
Secondary Outcome Measures
Progression Free Survival (PFS) of Participants with Triple Negative Breast Cancer (TNBC)
Invasive carcinoma of the breast
Triple-negative breast cancer