T-DM1 vs Paclitaxel/Trastuzumab for Breast (ATEMPT Trial)
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Trastuzumab; Paclitaxel; Trastuzumab emtansine
Intervention MeSH terms: Paclitaxel; Maytansine; Ado-Trastuzumab Emtansine; Trastuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 512.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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