T-DM1 vs Paclitaxel/Trastuzumab for Breast (ATEMPT Trial)
T-DM1 vs Paclitaxel/Trastuzumab for Breast (ATEMPT Trial)
This research study is a Phase II clinical trial. Phase II clinical trials test the
 effectiveness of an investigational drug to learn whether the drug works in treating a
 specific cancer. "Investigational" means that the drug is still being studied and that
 research doctors are trying to find out more about it-such as the safest dose to use, the
 side effects it may cause, and if the drug is effective for treating different types of
 cancer. It also means that the FDA has not approved this drug for use patients undergoing
 adjuvant treatment for HER2+ breast cancer. Trastuzumab emtansine (T-DM1) is a drug that may
 stop cancer cells from growing. This drug has been used in other research studies and
 information from those other research studies suggests that this drug may help to prevent the
 recurrence of breast cancer in this research study.

 The use of T-DM1 in this research study is experimental, which means it is not approved by
 any regulatory authority for the adjuvant treatment of HER2-positive breast cancer. However,
 it FDA-approved for metastatic HER2-positive breast cancer. T-DM1 has caused cancer cells to
 die in laboratory studies. In preclinical studies, this drug has prevented or slowed the
 growth of breast cancer. The breast cancer treatments (paclitaxel and Trastuzumab) used in
 this study are considered part of standard-of-care regimens in early breast cancer. A
 standard treatment means that this is a treatment that would be accepted by the majority of
 the medical community as a suitable treatment for your type of breast cancer.

 In this research study, the investigators are looking to see if the study drug T-DM1 will
 have less side effects than traditional HER2-positive breast cancer treatment of trastuzumab
 and paclitaxel. The investigators are also hoping to learn about the long term benefits and
 disease-free survival of participants who take the study drug T-DM1 in comparison to those
 participants to take the combination of trastuzumab and paclitaxel.
If a participant agrees to participate in this study she will be asked to undergo some
 screening tests or procedures to confirm that she is eligible. Many of these tests and
 procedures are likely to be part of regular cancer care and may be done even if turns out
 that she does not take part in this research study. If she has had some of these tests or
 procedures recently, they may or may not have to be repeated. These tests and procedures will
 include: a medical history, performance status, assessment of your tumor, blood tests,
 cardiac tests, pregnancy test and a collection of tumor tissue. If these tests show that she
 is eligible to participate in the research study, she will begin the study treatment. If she
 does not meet the eligibility criteria, she will not be able to participate in this research
 study.

 Because no one knows which of the study options is best, the participant will be "randomized"
 into one of the study groups after she has had her breast surgery: Group 1 or Group 2.
 Randomization means that she is put into a group by chance. Neither the participant nor the
 research doctor will choose what group she will be in. The participant will have a one in
 three chance of being placed in any group. Approximately 375 study participants will receive
 the study drug, while 125 study participants will receive the standard therapy of trastuzumab
 and paclitaxel.

 Group 1 participants will receive the study drug T-DM1 every three weeks by IV (intravenous
 injection) for 17 treatments (total of 51 weeks).

 Group 2 participants will receive the FDA-approved drugs Paclitaxel and Trastuzumab once per
 week by IV for 12 weeks. Then beginning week 13, participants will receive Trastuzumab only
 by IV injection every three weeks for the next 13 treatments.

 During all cycles the participant will have a physical exam and tumor assessment.

 The investigators would like to keep track of the participant's medical condition for the
 next five years after the final dose of study drug. The investigators would like to do this
 by regular visits every 6 months for 3 years after completion of study treatment, and then
 once a year for the next two years. The investigators may ask for additional follow-up by
 phone after completion of these visits.

 Participants who undergo lumpectomy (breast conserving surgery) need to receive breast
 radiation therapy to participate in this study. Participants who have undergone a mastectomy
 may receive chest wall and lymph node radiation (as determined by discussion with their
 physician). Radiation Therapy will begin after the conclusion of all study paclitaxel doses,
 and after 12 weeks fo the study drug T-DM1.
Inclusion Criteria:

 -  HER2-positive Stage I histologically confirmed invasive carcinoma of the breast

 -  ER/PR determination is required

 -  HER2 positive, confirmed by central testing: IHC 3+, FISH HER2/CEP17 <2.0 with an
 average HER2 copy number >/=6.0, or FISH HER2/CEP17 >/= 2.0

 -  Bilateral breast cancers that individually meet eligibility criteria are allowed

 -  Subjects with multifocal or multicentric disease are eligible as long as each tumor
 individually meets eligibility criteria

 -  Subjects with a history of ipsilateral DCIS are eligible if they were treated with
 wide-excision alone, without radiation therapy; Patients with a history of
 contralateral DCIS are not eligible.

 -  Should have tumor tissue available and a tissue block of sufficient size to make 15
 slides, which must be sent to a DFCI site for testing

 -  Less than or equal to 90 days since most recent breast surgery for this breast cancer

 -  All tumor should be removed by either a modified radical mastectomy or a segmental
 mastectomy (lumpectomy) with either a sentinel node biopsy or axillary dissection

 -  All margins should be clear of invasive cancer or DCIS

 -  May have received up to 4 weeks of tamoxifen therapy or other hormonal therapy, for
 adjuvant therapy for this cancer

 -  Prior oophorectomy for cancer prevention is allowed

 -  Subjects who have undergone partial breast radiation (duration </= 7 days) prior to
 registration are eligible. Partial breast radiation must be completed prior to 2 weeks
 before starting protocol therapy.

 -  Must have discontinued any investigational drug at least 2 weeks prior to
 participation

 -  Willing to use one highly effective from of nonhormonal contraception or two effective
 forms of nonhormonal contraception while on study and for 7 months after end of study
 treatment

 -  Subjects undergoing lumpectomy must have no contraindications to radiation therapy

 Exclusion Criteria:

 -  Pregnant or breastfeeding

 -  Use of potent CYP3A4 inhibitors during the study treatment period

 -  Excessive alcohol intake (more than 3 alcoholic beverages per day)

 -  Locally advanced tumors at diagnosis

 -  History of previous invasive breast cancer

 -  History of prior chemotherapy in the past 5 years

 -  History of prior trastuzumab or prior paclitaxel therapy

 -  Active, unresolved infection

 -  Active liver disease

 -  History of a different malignancy except for the following: disease free for at least
 5 years and at low risk for recurrence; cervical cancer in situ, basal or squamous
 cell carcinoma of the skin

 -  Active cardiac disease