Phase II Trial of Paclitaxel Combined With Trastuzumab and Pertuzumab as Pre-Operative Therapy for Inflammatory Breast Cancer
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
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 30
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, Day 1. It is given for a total of
6 doses. Trastuzumab is given weekly for a total of 17 weeks beginning on Week 1, Day 1.
Paclitaxel is given weekly for a total of 16 weeks beginning on Week 2, Day 8.
Study treatment visits will occur at regular intervals during the period of study treatment,
beginning on Week 1, Day 1. During these study treatment visits the following will be done:
physical exam, performance status, blood samples, heart function tests.
After completing 17 weeks of study treatment with trastuzumab, pertuzumab and paclitaxel,
you will undergo surgery for removal of your breast cancer. This will occur approximately
3-4 weeks after your last 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 3-4 weeks after surgery, when you are well-healed, you will begin chemotherapy
with doxorubicin and cyclophosphamide, known as AC. This is standard chemotherapy for IBC.
Doxorubicin will be given intravenously over about 5-10 minutes. This is followed by an
intravenous infusion of cyclophosphamide given over about 30 minutes. Anti-nausea medicine
is given first under the direction of your doctor. AC is given every 3 weeks for 4 doses (4
Cycles). Prior to each cycle, you will undergo the same procedure as that described above in
the study treatment visits.
Approximately 3-4 weeks after finishing the AC treatment, 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
Approximately 3-4 weeks following the completion of AC, 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 30 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 for a total of 12 doses. Every 9 weeks (every third dose of trastuzumab
and pertuzumab) you will undergo the same procedure as taht described above in Study
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Pathologic complete response rate
To determine pathologic complete response (pCR) rate after preoperative therapy with combination paclitaxel (T), trastuzumab (H) and pertuzumab (P) in HER2+ inflammatory breast cancer
Beth Overmoyer, MD
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Brigham and Women's Hospital||Boston, Massachusetts 02115|