A Study of Trastuzumab Emtansine (T-DM1) Sequentially With Anthracycline-based Chemotherapy, as Adjuvant or Neoadjuvant Therapy for Patients With Early Stage Herceptin (HER)2-positive Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01196052
First received: September 3, 2010
Last updated: May 27, 2014
Last verified: May 2014

September 3, 2010
May 27, 2014
October 2010
June 2013   (final data collection date for primary outcome measure)
  • Percentage of Participants With a Cardiac Event Within 12 Weeks After the Start of Trastuzumab Emtansine Treatment [ Time Frame: Baseline to 12 weeks after the start of trastuzumab emtansine treatment ] [ Designated as safety issue: Yes ]
    A cardiac event was defined as death from a cardiac cause or severe congestive failure (New York Heart Association [NYHA] Class III or IV) with a decrease in left ventricular ejection fraction (LVEF) of ≥ 10% from Baseline to an LVEF of < 50%.
  • Adverse Events, LVEF Function, and Deaths [ Time Frame: From the start to the end of trastuzumab emtansine treatment (up to 51 weeks) ] [ Designated as safety issue: Yes ]
    The following percentages of participants are reported: At least 1 adverse event while receiving T-DM1; at least 1 serious adverse event while receiving T-DM1; an adverse event leading to discontinuation, dose delay, or dose reduction of trastuzumab emtansine treatment; symptomatic cardiac dysfunction; and asymptomatic decline in left ventricular ejection fraction (LVEF). An asymptomatic LVEF decline was defined as a LVEF < 50% and a maximum decrease ≥ 10% from Baseline. The percentage of participants who died is reported.
  • Cardiac event rate [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: Yes ]
  • Safety of T-DM1 as measured by the incidence, nature and severity of adverse events [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01196052 on ClinicalTrials.gov Archive Site
  • Percentage of Participants Who Experienced at Least 1 Adverse Event During Concurrent Radiotherapy With Trastuzumab Emtansine Treatment [ Time Frame: From the start to the end of concurrent radiotherapy (up to 51 weeks) ] [ Designated as safety issue: Yes ]
  • Percentage of Participants Who Experienced at Least 1 Adverse Event During Concurrent Hormonal Therapy With Trastuzumab Emtansine Treatment [ Time Frame: From the start to the end of concurrent hormonal therapy (up to 51 weeks) ] [ Designated as safety issue: Yes ]
  • Percentage of Participants Who Completed the Planned Duration of Trastuzumab Emtansine Treatment [ Time Frame: From the start to the end of trastuzumab emtansine treatment (up to 51 weeks) ] [ Designated as safety issue: No ]
    Participants were to receive up to a total of 17 cycles of trastuzumab emtansine. If trastuzumab was given concurrently with either the optional docetaxel or optional radiation, then the number of 3-week cycles of trastuzumab therapy was subtracted from the planned 17 cycles of trastuzumab emtansine therapy.
  • Percentage of Participants Who Completed ≥ 95% of the Planned Radiotherapy Treatment With Concurrent Trastuzumab Emtansine Administration Without Significant (> 5 Days) Delay [ Time Frame: From the start to the end of radiotherapy treatment (up to 51 weeks) ] [ Designated as safety issue: No ]
  • Percentage of Participants With a Pathological Complete Response [ Time Frame: Day of surgery ] [ Designated as safety issue: No ]
    Pathological complete response was defined as the absence of invasive neoplastic cells at microscopic examination of the primary tumor and lymph nodes after surgery following primary systemic therapy. Pathological complete response was evaluated in participants treated with neoadjuvant therapy doxorubicin/cyclophosphamide-5-fluorouracil/epirubicin/cyclophosphamide followed by 1 or more doses of trastuzumab emtansine and who underwent surgery.
  • Disease-free Survival at Month 12 [ Time Frame: From the start of trastuzumab emtansine for adjuvant patients and from the date of surgery for neoadjuvant patients to 12 months later ] [ Designated as safety issue: No ]
    Disease-free survival was defined as the time from date of first protocol treatment for adjuvant patients or date of surgery for neoadjuvant patients to disease recurrence, occurrence of invasive contralateral breast cancer, other second primary cancer (excluding non-breast second primary), or death, whichever occurred first. Due to too few events, the analysis of disease-free survival was not performed.
  • pCR rate in patients treated with neoadjuvant therapy [ Time Frame: Up to 52 weeks ] [ 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 52 weeks ] [ Designated as safety issue: No ]
  • Feasibility and tolerability of the planned duration of T-DM1 with concurrent radiotherapy [ Time Frame: Up to 52 weeks ] [ Designated as safety issue: No ]
  • Feasibility and tolerability of the planned duration (up to 52 weeks) of T-DM1 [ Time Frame: Up to 52 weeks ] [ 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 ]
Not Provided
Not Provided
 
A Study of Trastuzumab Emtansine (T-DM1) Sequentially With Anthracycline-based Chemotherapy, as Adjuvant or Neoadjuvant Therapy for Patients With Early Stage Herceptin (HER)2-positive Breast Cancer
A Multicenter, Multinational Phase II Study to Assess the Clinical Safety and Feasibility of Trastuzumab Emtansine Sequentially With Anthracycline-based Chemotherapy, as Adjuvant or Neoadjuvant Therapy for Patients With Early Stage HER2-positive Breast Cancer

This single-arm open-label study assessed 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 received T-DM1 3.6 mg/kg intravenously on Day 1 of each 3-week cycle, for up to 17 cycles.

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
Drug: Trastuzumab emtansine
Trastuzumab emtansine was provided as a single-use lyophilized formulation in a glass vial.
Other Name: T-DM1
Experimental: Trastuzumab emtansine
Trastuzumab emtansine 3.6 mg/kg was administered intravenously on Day 1 of each 3-week treatment cycle up to a maximum of 17 cycles.
Intervention: Drug: Trastuzumab emtansine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
153
June 2013
June 2013   (final data collection date for primary outcome measure)

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).
  • Herceptin (HER)2-positive tumor, confirmed by central testing using immunohistochemistry (IHC) and in situ hybridization (ISH) methods.
  • Willingness to receive anthracycline-based chemotherapy or have received doxorubicin/cyclophosphamide (AC) OR 5-fluorouracil (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 2 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.
  • Human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Belgium,   France,   Germany,   Italy,   Korea, Republic of,   Russian Federation,   Spain
 
NCT01196052
BO22857, TDM4874g
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP