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A Randomized Phase II Trial of Neoadjuvant Cisplatin vs. Doxorubicin/Cyclophosphamide (AC) in Women With Newly Diagnosed Breast Cancer and Germline BrCa Mutations

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

A Randomized Phase II Trial of Neoadjuvant Cisplatin vs. Doxorubicin/Cyclophosphamide (AC) in Women With Newly Diagnosed Breast Cancer and Germline BrCa Mutations

If screening tests show that you are eligible to participate in the research study you will
begin study treatment. You will undergo a research biopsy so the study team can obtain
tissue samples. This will be used for biomarker research and will help your doctors to
better understand your disease, how the drug is working in your body, and may help to
identify which people may benefit most from platinum or from adriamycin/cytoxan in the

Because no one knows which of the study options is best, you will be "randomized" to receive
either cisplatin or doxorubicin and cyclophosphamide ("AC") chemotherapy prior to removal of
your breast cancer. Chemotherapy administered before the removal of the cancer is known as
neoadjuvant chemotherapy. Randomization means that you are put into a group by chance. It
is like flipping a coin. Neither you nor the research doctor will choose what group you will
be in. You will have an equal chance of being placed in either group.

If you are randomized to receive cisplatin you will receive cisplatin once every three weeks
for a total of four doses. You will be given cisplatin by vein (IV) on the first day of each
treatment cycle. The cisplatin infusion can take between 1 to 2 hours. Before and after
receiving cisplatin, you will receive fluid hydration by vein, and you will also be given
medicine to help prevent side effects such as nausea. The total time of the infusion of
cisplatin and the additional fluid and medications will take about 6 hours. After you
receive cisplatin, you will be asked to drink about 12 eight ounce glasses of fluid per day,
especially 2 or 3 days after therapy. The study treatment will stop if you have serious side
effects or if the tumor grows despite receiving cisplatin chemotherapy.

If you are randomized to "AC" chemotherapy you will receive both doxorubicin and
cyclophosphamide once every 2 or 3 weeks for a total of four doses by vein on the first day
of each treatment cycle. The interval between chemotherapy will be decided by your research
doctor. If you receive the chemotherapy every two weeks, you will also receive a
subcutaneous injection the day after chemotherapy. This injection contains a medicine that
contains a growth factor that will boost your immune system in order to allow your body to
be ready for chemotherapy in two weeks. The study treatment will be stopped if you have
serious side effects or if the tumor grows despite the doxorubicin and cyclophosphamide

At the beginning of each treatment cycle you will have a physical exam (including weight and
vital signs) and you will be asked general questions about your health and any medications
you may be taking, as well as specific questions about any side effects you may be
experiencing while receiving study treatment. Prior to each cycle of chemotherapy, you will
have standard blood tests to check your blood counts. If you are receiving cisplatin your
kidney function and body salts will also be checked prior to each chemotherapy cycle. In
addition, 7-10 days after chemotherapy your blood will be drawn to look at your blood cell
count to determine your risk of infection; if you have received cisplatin, your kidney
function and blood electrolytes will also be evaluated. The blood draw performed 7-10 days
after chemotherapy can be done in the hospital where you received your chemotherapy or
closer to home. About 1 tablespoon of blood will be drawn for these tests.

Surgery to remove your tumor will occur within six weeks after the last dose of
chemotherapy. Your surgery will be performed by your surgeon, as part of the standard care
for your disease.

Your treating physician or nurse practitioner will examine you to assess your tumor each
time you receive chemotherapy. A measurement of your tumor will be performed on the first
day of each treatment cycle as part of your physical exam. After the slides of your initial
breast cancer biopsy have been reviewed at your hospital, these slides and your tumor block
will be sent to the study pathologist at Beth Israel Deaconess Medical Center. Likewise,
after chemotherapy, your breast cancer will be removed by lumpectomy or mastectomy. After
these slides are reviewed at your hospital, they will also be sent with the tumor block to
the study pathologist so that the response of your tumor to the study treatment can be
assessed. After these slides are reviewed, they will be returned to the hospital at which
the biopsy and surgery were performed.

Decisions about whether you will receive more chemotherapy after your surgery is up to your
treating physicians. If you receive chemotherapy, the choice of chemotherapy is also up to
your doctors. Decisions about post-operative chemotherapy are not part of this study.

Inclusion Criteria:

- Pathologic confirmation of invasive breast cancer

- Stage: Clinical T1 > 1.5 cm, T2 or T3, N0-3, M0

- HER2 negative

- If tumor is ER+, it must be grade 2 or 3 or must have oncotype recurrence score > 31

- ER and PgR status by immunohistochemistry must be known

- Life expectancy greater than six months

- Use of an effective means of contraception is required

Exclusion Criteria:

- Pregnant or breastfeeding

- Prior chemotherapy at any time

- Prior treatment for the current breast cancer, including chemotherapy, hormonal
therapy, radiation or experimental therapy

- Ipsilateral breast recurrence, unless prior treatment consisted of excision alone for
DCIS or breast-conserving treatment and hormonal therapy for DCIS or invasive cancer

- Peripheral neuropathy of any etiology that exceeds grade 1

- Significant hearing loss

- Renal dysfunction

- Use of other investigational or study agents

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to study drugs

- Uncontrolled intercurrent illness

- Any condition that would prohibit administration of corticosteroids

- Uncontrolled diabetes

- Pre-existing medical condition that would represent toxicity in excess of grade 1 as
measured by CTCAE

- Known HIV positive individuals on combination antiretroviral therapy

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

pCR to neoadjuvant cisplatin vs. pCR to AC

Outcome Description:

To determine if the pathologic complete response (pCR) rate (determined by the Miller-Payne method) to neoadjuvant cisplatin is at least 20% greater than the pCR to doxorubicin/cyclophosphamide (AC) in women with newly diagnosed breast cancer and a germline BRCA mutation.

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Nadine Tung, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beth Israel Deaconess Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

October 2012

Completion Date:

June 2016

Related Keywords:

  • Breast Cancer
  • germline mutation
  • BRCA1 mutation
  • BRCA2 mutation
  • Breast Neoplasms



Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
University of Colorado Cancer CenterDenver, Colorado  80262
Beth Israel Deaconess Medical CenterBoston, Massachusetts  02215
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Massachusetts General HospitalBoston, Massachusetts  02114-2617
The Cancer Institute of New JerseyNew Brunswick, New Jersey  08901
University of Pennsylvania Abramson Cancer CenterPhiladelphia, Pennsylvania  19104
Women and Infants HospitalProvidence, Rhode Island  02905
Yale School of MedicineNew Haven, Connecticut  06510
Cedars Sinai HospitalLos Angeles, California  90048
Dana-Farber Cancer Institute at Faulkner HospitalBoston, Massachusetts  02215