This research study is a Phase II clinical trial, which tests the safety and effectiveness of
an investigational drug to learn whether the drug works in treating a specific cancer. In
this study, paclitaxel and trastuzumab are being combined with pertuzumab which is
"investigational" for the preoperative treatment of inflammatory breast cancer. Trastuzumab
is given for a total of 12 months for the treatment of HER2 positive breast cancer. This
study also adds pertuzumab to trastuzumab so that both drugs are given for a total of 12
months; this combination is also "investigational".
"Investigational" means that pertuzumab is being studied. It also means that although the FDA
has approved pertuzumab for preoperative use to treat breast cancer, it has not been
thoroughly studied in combination with paclitaxel and trastuzumab for preoperative treatment
of inflammatory breast cancer. It has been FDA approved for specific use in advanced breast
cancer that is HER2 positive.
Pertuzumab is an antibody, which is a protein that attacks a foreign substance is the body.
Pertuzumab blocks the function of the HER2 protein like trastuzumab does. However, pertuzumab
binds to a different part of the HER2 receptor and stops cancer cells from growing. This drug
has been used in the treatment of advanced breast cancer that is HER2 positive, and has been
combined with trastuzumab and chemotherapy in those studies. Information from those other
research studies suggests that pertuzumab may help to kill the cancer cells in the breast and
enable you to undergo a mastectomy. The addition of pertuzumab may also help reduce the
chance of cancer recurrence.
In this research study, we are combining pertuzumab with paclitaxel and trastuzumab as
preoperative therapy and will determine the response of the cancer remaining in the breast at
the time of mastectomy. In addition, we are combining trastuzumab with pertuzumab for a total
of 12 months and we are looking to see whether the combination reduces the chance that the
cancer will return.
Another goal of this research study is to determine whether we can develop a way to identify
tumors that will respond well to this study treatment. We will do research tests on your
tumor tissue before, during and after study treatment. These tests may help doctors
understand how the study treatment may work to treat your type of breast cancer. In the
future, these tests may help us find ways to help match patients with the drugs most likely
to work against their specific tumors before treatment begins.
If you agree to take part in this study we will ask you to undergo some screening tests and
procedures to confirm that you are eligible. Many of these tests and procedures are likely to
be part of regular cancer care and may be done even if it turns out that you do not take part
in the research study. If you have had some of these tests or procedures recently, they may
or may not have to be repeated. The screening process will include the following: a medical
history, performance status, physical examination, scans and x-rays, blood samples, blood
pregnancy test, electrocardiogram, echocardiogram. If these tests show that you are eligible
to participate in the research study, you will begin the study treatment. If you do not meet
the eligibility criteria you will not be able to participate in this research study.
Before beginning study treatment you will undergo a tumor biopsy and have photographs of your
tumor taken to assess the response of your tumor to the study treatment.
On the first day of study treatment (Week 1, Day 1) with trastuzumab and pertuzumab, you will
receive an intravenous infusion of trastuzumab over about 90 minutes, followed by a 60
minutes observation period. If the trastuzumab infusion is tolerated, you will receive the
rest of your study treatment, the pertuzumab. This will also be given as an intravenous
infusion over about 60 minutes with you being observed for a further 60 minutes. Thus, the
total duration of infusion and observation periods for the first dose of study treatment
(Week 1, Day 1) is about 5 hours. If the drugs are well tolerated at Week 1, the duration of
the infusion with trastuzumab and pertuzumab may be shortened for subsequent doses.
Prior to starting Week 2, you will undergo a second research biopsy of your breast. The
biopsy will be performed either prior to Week 2, Day 8 or on the same day. You will then
receive an infusion of trastuzumab and begin chemotherapy. If the infusion of trastuzumab was
tolerated on Week 1, Day 1, then the infusion time is reduced to about 30 minutes. You will
then be pre-medicated with drugs to reduce the chance of having a sensitivity reaction to
paclitaxel. This takes approximately 30 minutes. The paclitaxel is give by intravenous
infusion over about 60 minutes. If you tolerate the paclitaxel infusions, then the
pre-medication can be changed by your doctor.
The pertuzumab is given every 3 weeks beginning on Week 1 and continues until paclitaxel
administration is complete. Trastuzumab is given weekly beginning on Week 1 and continues
until paclitaxel administration is complete. Paclitaxel is given weekly for a total of 16
doses beginning on Week 2. After completing 16 doses of paclitaxel, trastuzumab and
pertuzumab may be continued every 3 weeks until surgery.
Study treatment visits will occur at regular intervals during the period of study treatment,
beginning on Week 1. During these study treatment visits the following will be done: physical
exam, performance status, blood samples, heart function tests.
After completing 16 doses of paclitaxel in combination with pertuzumab and trastuzumab, you
will undergo surgery for removal of your breast cancer. This will occur approximately 4-5
weeks after your last paclitaxel infusion. Prior to surgery, you will have the following
assessments: a repeat breast MRI, PET scan (if necessary), physical exam, vital signs,
performance status, blood tests, tumor tissue tests.
Approximately 4-5 weeks after surgery, when you are well-healed, you will have two options
for treatment (at your physician's discretion):
Option 1: Doxorubicin and cyclophosphamide (AC), every 2-3 weeks x 4 cycles. This is standard
chemotherapy for IBC. Followed by trastuzumab and pertuzumab every 3 weeks to complete 12
months of HER2-directed therapy.
Option 2: Continue trastuzumab and pertuzumab every 3 weeks to complete 12 months of
Doxorubicin is given by vein over about 5-10 minutes. This is followed by cyclophosphamide by
vein given about 30 minutes. Anti-nausea medicine is given first under the direction of your
Approximately 4-5 weeks after finishing the AC treatment if you pursue Option 1 (or 4-5 weeks
after surgery if you pursue Option 2), you will receive radiation therapy to the mastectomy
site and the surrounding lymph nodes. This will be given daily, Monday through Friday for
approximately 6-7 weeks. This will be administered as standard of care for IBC.
Approximately 3-4 weeks following the completion of AC if you pursue Option 1 (or 3-4 weeks
after surgery if you pursue Option 2), you will begin maintenance therapy with trastuzumab
and pertuzumab. As with Week 1, Day 1, you will receive an intravenous infusion of
trastuzumab over about 90 minutes followed by a 60 minute observation period. If the
trastuzumab infusion is tolerated, you will receive the rest of your study treatment, the
pertuzumab. This will also be given as an intravenous infusion over about 60 minutes with
your being observed for a further 60 minutes. Thus, the total duration of infusion and
observation periods for the first day of maintenance study treatment is about 5 hours. If the
study drugs are well tolerated, the duration of the infusion with trastuzumab and pertuzumab
may be shortened for subsequent doses. Both trastuzumab and pertuzumab will be given every 3
weeks to complete a 12 month duration of HER2-directed therapy. Every 9 weeks (every third
dose of trastuzumab and pertuzumab) you will undergo the same procedure as taht described
above in Study Treatment visits.
About one month after your last dose of study treatment, you will be asked to return to the
clinic. At this visit tests will be done to check your physical condition and to check that
you have recovered from any side effects of study treatment. During this visit the following
will be done: physical exam, vital signs, performance status and blood tests.
You will be asked to attend regular follow up visits to check if you are experiencing any
long term side effects and to check taht the cancer has not come back. We plan to follow
participants for up to 13 years after the start of teh study. During these visits the
following will be done: physical exam and questions about your health/medications you have
taken (every 3 months for the first year, every 6 months for the next 4 years, yearly until
the end of study follow up); blood draws (every 6 months for the first 4 years, yearly after
that); mammograms will be performed annually, other scans may be performed as needed.
- Histologically confirmed invasive breast cancer
- HER2 positive breast cancer
- Clinical diagnosis of inflammatory breast cancer
- Without evidence of visceral or bone involvement with metastatic cancer on physical
exam or any diagnostic study. Extensive nodal involvement is allowed
- Willingness to undergo a research biopsy of the affected breast
- Prior therapy for the treatment of breast cancer
- Receiving any other investigational or commercial agents or therapies
- Known brain metastases
- Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs
resulting in dyspnea at rest
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to paclitaxel, trastuzumab, pertuzumab
- Uncontrolled intercurrent illness
- Pregnant or breastfeeding
- History of a different malignancy except for the following circumstances: disease-free
for at least 5 years and at low risk of recurrence, or cervical cancer in situ or
basal or squamous cell carcinoma of the skin
- HIV positive on combination anti-retroviral therapy