Women's Triple-Negative First-Line Study: A Phase II Trial of Panitumumab, Carboplatin and Paclitaxel (PaCT) in Patients With Localized Triple-Negative Breast Cancer (TNBC) With Tumors Predicted Insensitive to Standard Neoadjuvant Chemotherapy

Study Drug Administration:

About 1 week before Cycle 1, if you are found to be eligible to take part in this study, you
will receive a single dose of panitumumab by vein over about 1 hour.

You will then receive the study drug combination for 4 cycles. Each cycle is 21 days.

On Day 1 of each Cycle, you will receive panitumumab, carboplatin, and paclitaxel by vein.
Panitumumab will be given over 30-60 minutes, paclitaxel over about 2 hours, and carboplatin
over about 2 hours.

On Days 8 and 15 of each cycle, you will receive panitumumab and paclitaxel by vein following
the same timing as Day 1.

If you have side effects, the study doctor may decide to lower the study drug dose(s) or to
have you stop taking the drug(s). You may be able to restart the study drug(s) later at the
same or a lower dose. The study doctor will discuss this with you.

Study Visits:

About 1 week before Cycle 1, the same day that you receive the single dose of Panitumumab,
you will have blood drawn (about 2 teaspoons) for pharmacokinetic (PK) testing. PK testing
measures the amount of study drug in the body at different time points.

About 1 week after the first panitumumab dose, you will have blood drawn (about 2 teaspoons)
for PK testing.

On Day 1 of each cycle:

- You will have a physical exam.

- Blood (about 2 teaspoons) will be drawn for routine tests.

On Days 8 and 15 of each cycle, blood (about 2 teaspoons) will be drawn for routine tests.

On Day 21 (+/- 1 day) of Cycle 2, blood (about 2 teaspoons) will be drawn for PK testing.

Surgery:

After you have received 4 cycles of chemotherapy, or at any time that the disease appears to
get worse, you will have an MRI, mammogram, or ultrasound to check the status of the disease.
Based on the scans, the doctor will decide the type of surgery that you will have to remove
the tumors.You will be given a separate surgery consent form that describes the procedure and
its risks. If you come off study, you may be offered chemotherapy, more surgery, or another
option.

At the time of your surgery, blood (about 2 teaspoons) will be drawn for PK testing.

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 at least 2 years after surgery.

Follow-Up:

Every 3-4 months, the study team will track your standard of care physical exam visits.

This is an investigational study. Paclitaxel and carboplatin are FDA approved and
commercially available for the treatment of breast cancer. Panitumumab is FDA approved and
commercially available for the treatment of colorectal cancer. It is currently being used for
research purposes only in the breast cancer setting. The study doctor can explain how the
study drugs are designed to work.

Up to 37 participants will be enrolled in this study. All will take part at MD Anderson.

Inclusion Criteria:

1. Patients must have an intact evaluable primary tumor or biopsy proven axillary node
involvement with at least 1.0 cm smallest dimension based on imaging after neoadjuvant
anthracycline-based chemotherapy and prior to initiation of neoadjuvant chemotherapy
under this protocol. Baseline measurements and evaluations must be obtained within 4
weeks of registration to the study. All areas of disease should be recorded in order
to assess response and uniformity of response to therapy.

2. 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.

3. Age >/= 18 years.

4. Patients must have an ECOG performance status of 0 or 1.

5. Patients must have received at least one dose of an anthracycline based neoadjuvant
regimen. Patients are eligible if therapy was discontinued due to disease progression
or therapy intolerance.

6. Baseline MUGA or echocardiogram showing LVEF >/= 50% within 6 weeks prior to
initiation of neoadjuvant chemotherapy.

7. 7) Adequate organ function defined by the following parameters • Serum creatinine 1.5 mg/dl. Creatinine clearance (CrCl) >/= 50 mL/min calculated by the Cockcroft-Gault
method as follows: male creatinine clearance = (140 - age in years) x (weight in kg) /
(serum Cr x 72); Female CrCl = (140 - age in years) x (weight in kg) x 0.85 / (serum
Cr x 72). • ANC>/= 1500/mm^3, platelets >/= 100,000/mm^3 • Hemoglobin >/=9.0 g/dL •
SGOT (AST) and SGPT (ALT)< 3.0 x upper limit of normal • Alkaline phosphatase (Alp)

8. Signed informed consent.

Exclusion Criteria:

1. Patient is unwilling or unable to sign and date the IRB approved informed consent.

2. Patients with less than 1.0 cm measurable residual disease after neoadjuvant
anthracycline based chemotherapy.

3. Women that are pregnant or lactating.

4. Patients with a history of prior malignancy within 5 years of study entry with the
exception of curatively treated non-melanomatous skin cancer or carcinoma in situ of
the cervix or breast.

5. Patients with a history of stage IV or metastatic disease.

6. Any serious medical illness, other than that treated by this study, which would limit
survival to less than 1 month or psychiatric illness which would limit informed
consent.

7. Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus,
acute or chronic active hepatitis B infection.

8. Patients with a peripheral neuropathy > grade 1.

9. Patients with a history of serious cardiac events defined as: New York Heart
Association class 3 or 4 heart failure, or history of myocardial infarction, unstable
angina or CVA within 6 months of protocol registration.

10. Patients with a history of PR prolongation or AV block.

11. Patients with a history of prior therapy with paclitaxel and/or carboplatin.

12. Patients who have received a cumulative dose of doxorubicin of greater than 360 mg/m^2
or epirubicin of greater than 640 mg/m^2.

13. Patients who concurrently use hormonal therapy and/or concurrent radiation therapy.

14. Patients who had prior radiation therapy of the primary breast carcinoma or axillary
lymph nodes.

15. 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 the following: • Placement of an intrauterine device (IUD) or intrauterine
system (IUS); • Barrier methods of contraception: condom or occlusive cap (diaphragm
or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository; •
Total abstinence or; • Male/female sterilization.

16. Continued from #15: Women are considered post-menopausal and not of child-bearing
potential if they have had 12 months of natural (spontaneous) amenorrhea with an
appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or
have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal
ligation at least six weeks prior to treatment. In the case of oophorectomy alone,
only when the reproductive status of the woman has been confirmed by follow up hormone
level assessment is she considered not of child-bearing potential.

17. 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.

18. Negative serum or urine pregnancy test for women within 72 hours of receiving the
first dose of the study medication for women of childbearing potential.