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A Study of Trastuzumab Emtansine (T-DM1) Sequentially With Anthracycline-Based Chemotherapy, As Adjuvant or Neoadjuvant Therapy for Patients With Early Stage HER2-Positive Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01196052
First received: September 3, 2010
Last updated: June 3, 2013
Last verified: June 2013
History of Changes
  Purpose

This single-arm open-label study will assess the safety, feasibility and efficacy of trastuzumab emtansine (T-DM1) after the completion of anthracycline-based adjuvant/neoadjuvant chemotherapy in patients with early HER2-positive breast cancer. Patients will receive T-DM1 3.6 mg/kg intravenously on Day 1 of each 3-week cycle, for up to 17 cycles.


Condition Intervention Phase
Breast Cancer
 Drug: trastuzumab emtansine
 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Multinational Phase II Study to Assess the Clinical Safety and Feasibility of T-DM1 Sequentially With Anthracycline-Based Chemotherapy, As Adjuvant or Neoadjuvant Therapy for Patients With Early Stage HER2-Positive Breast Cancer

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Rate of cardiac events, defined as death from cardiac cause or severe congestive heart failure (NYHAC Class III or IV) with a decrease in LVEF of >/=10 absolute % points from baseline to an LVEF of <50% [ Time Frame: up to 51 weeks (17 cycles) of treatment + 6 months follow-up ] [ Designated as safety issue: Yes ]
  • Safety of T-DM1 as measured by the incidence, nature and severity of adverse events [ Time Frame: Up to 51 weeks (17 cycles) of treatment + 6 months follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pathological complete response (pCR) rate in patients treated with neoadjuvant therapy [ Time Frame: Up to 51 weeks (17 cycles) ] [ Designated as safety issue: No ]
  • Safety of T-DM1 with concurrent radiotherapy and in patients who receive concurrent hormonal therapy will be measured by the incidence, nature, and severity of Adverse Events [ Time Frame: Up to 51 weeks (17 cycles) ] [ Designated as safety issue: No ]
  • Feasibility and tolerability of the planned duration of T-DM1 with concurrent radiotherapy [ Time Frame: Up to 51 weeks (17 cycles) ] [ Designated as safety issue: No ]
  • Feasibility and tolerability of the planned duration (up to 17 cycles) of T-DM1 [ Time Frame: Up to 51 weeks (17 cycles) ] [ Designated as safety issue: No ]
  • Disease-free survival (DFS) rate in patients treated with neoadjuvant therapy [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • DFS rate in patients treated with adjuvant therapy [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 153
Study Start Date: October 2010
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: trastuzumab emtansine
3.6 mg/kg iv on Day 1 of each 3-week cycle, up to 17 cycles

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Locally advanced, inflammatory, or early stage, unilateral, and histologically confirmed invasive breast cancer documented at a local laboratory (Patients with inflammatory breast cancer must be able to have a core needle biopsy)
  • HER2-positive tumor, confirmed by central testing using IHC and ISH methods
  • Willingness to receive anthracycline-based chemotherapy or have received doxorubicin/cyclophosphamide (AC) OR 5-FU/epirubicin/cyclophosphamide (FEC) in a similar dose and schedule as described in the protocol as part of neoadjuvant or adjuvant treatment
  • For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of contraception or two effective forms of non-hormonal contraception by the patient and/or partner. Contraception use must continue for the duration of study treatment and for at least 6 months after the last dose of study treatment. Male patients should use condoms for the duration of the study. Specific country requirements will be followed.
  • Negative results of serum pregnancy test for premenopausal women of reproductive capacity and for women < 12 months after menopause
  • Patients may enroll before or after AC/FEC chemotherapy has completed.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate hematologic, biochemistry and cardiac assessments

Exclusion Criteria:

  • Stage IV breast cancer or bilateral breast cancer
  • Pregnant or breastfeeding women
  • History of other malignancy within the previous 5 years, except contralateral breast cancer and ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS), appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with outcome similar to those mentioned above
  • Radiation therapy, immunotherapy, or biotherapy within 5 years before study enrollment; non-cardiotoxic chemotherapy for malignancy treated > 5 years before study enrollment is allowed. Patients receiving AC/FEC in a similar fashion to the study treatment prescribed for adjuvant or neoadjuvant treatment of breast cancer will be allowed to enroll in the study after the completion of their AC/FEC. No other prior history of cardiotoxic chemotherapy is allowed.
  • Active cardiac history
  • Current chronic daily treatment with oral corticosteroids or equivalent
  • Patients with severe dyspnea at rest or requiring supplementary oxygen therapy
  • Active, unresolved infections at screening
  • HIV, HBV or HCV infection
  • Major surgery within 4 weeks before enrollment that is unrelated to the breast cancer
  • Patients for whom concomitant radiotherapy + T-DM1 may be contraindicated yet radiation therapy is planned
  • Known hypersensitivity to any of the study drugs or derivatives, including murine proteins
  • Grade >/= 2 peripheral neuropathy at baseline
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01196052

  Show 44 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01196052     History of Changes
Other Study ID Numbers: BO22857, TDM4874g
Study First Received: September 3, 2010
Last Updated: June 3, 2013
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on June 13, 2013