A Phase II Study of Using Panitumumab/Carboplatin/Paclitaxel (PaCT) Followed by Anthracycline-Containing Regimen (AC) for New Triple-Negative Inflammatory Breast Cancer (TN-IBC)

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as
in the flip of a coin) to 1 of 2 study groups. You will have an equal (50/50) chance of being
assigned to either group, and you and the study staff will know what you are receiving:

- If you are in Group A, you will receive panitumumab, carboplatin, and paclitaxel,
followed by doxorubicin and cyclophosphamide.

- If you are in Group B, you will receive carboplatin and paclitaxel, followed by
doxorubicin and cyclophosphamide.

Study Drug Administration:

Every study cycle will be 21 days.

You will receive paclitaxel by vein over about 1-3 hours on Days 1, 8, and 15 of Cycles 1-4.

You will receive carboplatin by vein over about 30 minutes on Day 1 of Cycles 1-4.

If you are in Group A, you will also receive panitumumab by vein. You will first receive it
over about 1 hour on Day 1 of a 1-week "pre-cycle." You will then receive it over about 30
minutes on Days 1, 8, and 15 of Cycles 1-4, before you receive paclitaxel.

You will then receive standard of care doxorubicin and cyclophosphamide by vein over about 90
minutes on Day 1 of Cycles 5-8.

This schedule may be changed if the study doctor thinks it is needed.

Study Visits:

For both Groups A and B:

- Every day that you receive the study drugs, and then at any time before surgery and
after the last dose of doxorubicin and cyclophosphamide, blood (about 1½ to 3
tablespoons) will be drawn for routine tests.

- Before each cycle , and then at any time before surgery and after the last dose of
doxorubicin and cyclophosphamide, you will have a physical exam including a breast and
lymph node exam.

- On Day 1 of Cycle 1, then 1 time before you begin receiving doxorubicin and
cyclophosphamide, and then 1 time before surgery, the study doctor will take pictures of
both of your breasts.

- Before receiving any treatment, on Day 1 of Cycle 1, then 1 time before you begin
receiving doxorubicin and cyclophosphamide, and then 1 time before surgery , blood
(about 5 tablespoons) will be drawn for cytokine testing.

- One (1) time before you begin receiving doxorubicin and cyclophosphamide , you will have
a mammogram of the involved breast and an ultrasound of the involved breast and lymph
nodes. You may have a breast MRI if the doctor thinks it is needed.

If you are in Group A, you will have a breast core biopsy before Day 1 of Cycle 1 for
biomarker testing.

This schedule may be changed if the study doctor thinks it is needed.

Surgery:

After you have finished receiving doxorubicin and cyclophosphamide, you will have standard of
care surgery. You will be given a separate consent form to read and sign.

During surgery, breast tissue samples will be collected to identify tumors for routine
testing and for biomarker testing.

Length of Study:

You may continue taking the study drugs for up to 8 cycles. 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 period.

Follow-Up:

About 1 month after surgery, you will be asked about your health and any side effects you may
have had. You may be asked during a routine clinic visit or you may be called by a member of
the study staff. If you are called, each call should last about 2 minutes.

One (1) time every year for at least 5 years after you stop taking the study drugs, you will
be contacted and asked about how you are doing. If you are called, each call should last
about 2 minutes. This may also be done in a regular clinic visit.

Inclusion Criteria:

1. Patients must have histological confirmation of breast carcinoma.

2. Patients must have IBC, confirmed according to international consensus criteria: a.
Onset: Rapid onset of breast erythema, edema, and/or peau d'orange, and/or warm
breast, with or without an underlying breast mass b. Duration: History of such
findings no more than 6 months c. Extent: Erythema occupying at least 1/3 of whole
breast d. Pathology: Pathologic confirmation of invasive carcinoma

3. Patients must have an ECOG performance status of 0-1.

4. Patients must have negative HER2 expression on IHC (defined as 0 or 1+) or FISH
analysis. If HER2 is 2+, negative HER2 expression must be confirmed by FISH
(HER2/cep17 ration <2, and/or copy number less than 6). ER and PgR expression should
be less than 10%.

5. Patients must be 18 years of age or older.

6. Patients have LVEF >=50% by multigated acquisition scan (MUGA) or echocardiogram
before study randomization

7. Patients have adequate hematologic function: absolute neutrophil count (ANC) >=1.5 x
10^9/L, platelet count >=100 x 10^9/L, hemoglobin >= 9.0 g/dL.

8. Patients have adequate hepatic function: aspartate aminotransferase (AST) =<3.0 x ULN,
alanine aminotransferase (ALT) =< 3.0 x ULN, alkaline phosphatase (ALP) =< 2.5 x ULN,
total bilirubin =<1.5 x ULN

9. Patients have adequate renal function: creatinine (Cr) =< 1.5 mg/dL x ULN, 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).

10. Patients have the ability and willingness to sign written informed consent.

11. Patients of childbearing potential (women who are postmenopausal for <1 year, not
surgically sterilized, or not abstinent), have a negative urine pregnancy test, and
agree to the consistent and correct use of one of the following acceptable methods of
birth control: male partner who is sterile before the female subject's entry into the
study and is the sole sexual partner for that female subject; intrauterine device,
oral contraception, or barrier methods, including diaphragm or condom with a
spermicide

Exclusion Criteria:

1. Stage IV disease, if the metastatic sites are not amendable for local therapy (i.e.
radiation and/or surgery), and are not candidates for breast surgery will not be
eligible.

2. History of radiotherapy for current breast cancer diagnosis.

3. History of recent malignancies <5 years (except for cured non-melanomatous skin cancer
or cured cervical carcinoma in situ)

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

5. History of extensive interstitial lung disease, e.g., pneumonitis or pulmonary
fibrosis or any evidence of extensive interstitial lung disease on baseline chest CT
scan.

6. Other known other significant medical or psychiatric condition that would make
assessment of toxicity or efficacy difficult.

7. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

8. Patients with a peripheral neuropathy > grade 1.

9. Patients with a history of 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 have a history of prior therapy with carboplatin.

11. Patients have received a cumulative dose of doxorubicin of greater than 360 mg/m2 or
epirubicin of greater than 640 mg/m2.

12. Patients have had prior radiotherapy for primary breast carcinoma or axillary lymph
nodes.

13. Patients have history of diagnosed interstitial lung disease.