T-DM1 vs Paclitaxel/Trastuzumab for Breast (ATEMPT Trial)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Dana-Farber Cancer Institute
Sponsor:
Information provided by (Responsible Party):
Sara Tolaney, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01853748
First received: April 24, 2013
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Trastuzumab
Drug: Paclitaxel
Drug: Trastuzumab emtansine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Trastuzumab Emtansine (T-DM1) vs. Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT Trial)

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Disease Free Survival in Patients Treated with T-DM1 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Disease-free survival (DFS) in patients with Stage I HER2-positive breast cancer treated with trastuzumab emtansine


Secondary Outcome Measures:
  • Disease Free Survival in Patient Groups Defined by Tumor Size [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Disease free survival in patient groups defined by tumor size (< 1cm or >/= 1 cm and hormone receptor status who are treated with trastuzumab emtansine

  • Percentage of participants with Grade 3-4 Cardiac Dysfunction [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The incidence of grade 3-4 cardiac left ventricular dysfunction from adjuvant trastuzumab emtansine and paclitaxel and trastuzumab

  • Percentage of participants with T-DM1 Induced Grade 2-4 Thrombocytopenia [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Calculate the incidence of trastuzumab emtansine-induced grade 2-4 thrombocytopenia

  • Percentage of Patients with Amenorrhea at specific time points [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Investigate the percentage of patients with amenorrhea at various times after start of treatment in premenopausal women receiving treatment with trastuzumab emtansine and paclitaxel and trastuzumab for early stage breast cancer

  • Overall Survival in Patients Treated with T-DM1 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Calculate overall survival in participants treated with trastuzumab emtansine


Estimated Enrollment: 500
Study Start Date: May 2013
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Study Drug
T-DM1 every three weeks by IV for a total of 17 weeks
Drug: Trastuzumab emtansine
Other Name: T-DM1
Active Comparator: Standard of Care
Paclitaxel and Trastuzumab once per week by IV for 12 weeks. Beginning week 13, Trastuzumab only by IV injection every three weeks for 13 weeks
Drug: Trastuzumab Drug: Paclitaxel

Detailed Description:

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 A or Group B. 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 A participants will receive the study drug T-DM1 every three weeks by IV (intravenous injection) for a total of 17 weeks.

Group B 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 weeks.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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+ or FISH HER2/CEP17 >/= 2
  • 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 6 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01853748

Contacts
Contact: Sara Tolaney, MD, MPH 6176322335 stolaney@partners.org

  Show 27 Study Locations
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Principal Investigator: Sara Tolaney, MD, MPH Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Sara Tolaney, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01853748     History of Changes
Other Study ID Numbers: 13-048
Study First Received: April 24, 2013
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Maytansine
Ado-trastuzumab emtansine
Trastuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014