A Study of the Efficacy and Safety of Trastuzumab Emtansine (Trastuzumab-MCC-DM1) vs. Trastuzumab (Herceptin®) and Docetaxel (Taxotere®) in Patients With Metastatic HER2-positive Breast Cancer Who Have Not Received Prior Chemotherapy for Metastatic Disease

NCT ID: NCT00679341

Last Updated: 2014-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 137 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2012-05-31

Brief Summary

This was a Phase II, randomized, multicenter, international, 2-arm, open-label clinical trial designed to explore the efficacy and safety of trastuzumab emtansine (T-DM1) relative to the combination of trastuzumab and docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive, unresectable, locally advanced breast cancer and/or metastatic breast cancer who have not received prior chemotherapy for metastatic disease.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Trastuzumab emtansine

Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) administered over 30-90 minutes every 3 weeks on Day 1 of each 21-day cycle.

Group Type: EXPERIMENTAL

Trastuzumab emtansine [Kadcyla]

Intervention Type: DRUG

The total dose depended on the patient's weight on Day 1 of each cycle. Trastuzumab emtansine was administered every 3 weeks until investigator-assessed radiographic or clinical progressive disease (or until second disease progression for patients who crossed over), unacceptable toxicity, or study closure, whichever occurred first.

Trastuzumab + docetaxel

Patients received a loading dose of trastuzumab 8 mg/kg IV + docetaxel 75 or 100 mg/m\^2 IV on Day 1 of Cycle 1 followed by trastuzumab 6 mg/kg IV + docetaxel 75 or 100 mg/m\^2 IV on Day 1 of all subsequent 21-day cycles.

Group Type: ACTIVE_COMPARATOR

Trastuzumab

Intervention Type: DRUG

The dose of trastuzumab was recalculated if body weight changed by more than ±10% from baseline. Trastuzumab was administered every 3 weeks until investigator-assessed radiographic or clinical progressive disease, or unmanageable toxicity. Patients in the trastuzumab + docetaxel arm who discontinued study treatment because of progressive disease were eligible to cross-over to trastuzumab emtansine treatment until a second progressive disease event, clinical deterioration, and/or intolerance.

Docetaxel

Intervention Type: DRUG

Docetaxel was given at a dose of 75 or 100 mg/m\^2 based on the investigator's decision. Patients in the trastuzumab + docetaxel arm who discontinued study treatment because of progressive disease were eligible to cross-over to trastuzumab emtansine treatment until a second progressive disease event, clinical deterioration, and/or intolerance.

Interventions

Trastuzumab emtansine [Kadcyla]

The total dose depended on the patient's weight on Day 1 of each cycle. Trastuzumab emtansine was administered every 3 weeks until investigator-assessed radiographic or clinical progressive disease (or until second disease progression for patients who crossed over), unacceptable toxicity, or study closure, whichever occurred first.

Intervention Type: DRUG

Trastuzumab

The dose of trastuzumab was recalculated if body weight changed by more than ±10% from baseline. Trastuzumab was administered every 3 weeks until investigator-assessed radiographic or clinical progressive disease, or unmanageable toxicity. Patients in the trastuzumab + docetaxel arm who discontinued study treatment because of progressive disease were eligible to cross-over to trastuzumab emtansine treatment until a second progressive disease event, clinical deterioration, and/or intolerance.

Intervention Type: DRUG

Docetaxel

Docetaxel was given at a dose of 75 or 100 mg/m\^2 based on the investigator's decision. Patients in the trastuzumab + docetaxel arm who discontinued study treatment because of progressive disease were eligible to cross-over to trastuzumab emtansine treatment until a second progressive disease event, clinical deterioration, and/or intolerance.

Intervention Type: DRUG

Other Intervention Names

trastuzumab-DM1; trastuzumab-MCC-DM1; T-DM1; Herceptin; Taxotere

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed adenocarcinoma of the breast with locally advanced or metastatic disease, and a candidate for chemotherapy.
• Human epidermal growth factor receptor 2 (HER2)-positive.
• No prior chemotherapy for their metastatic breast cancer (MBC).
• Measurable disease.
• Age ≥ 18 years.
• 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 whose partners are pregnant should use condoms for the duration of the study.

Exclusion Criteria

• History of any chemotherapy for MBC.
• An interval of < 6 months from the completion of cytotoxic chemotherapy in the neo-adjuvant or adjuvant setting until the time of metastatic diagnosis.
• Trastuzumab ≤ 21 days prior to randomization.
• Hormone therapy < 7 days prior to randomization.
• Current peripheral neuropathy of Grade ≥ 3.
• History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome as those previously mentioned.
• Previous radiotherapy for the treatment of unresectable, locally advanced or metastatic breast cancer is not allowed if more than 25% of marrow-bearing bone has been irradiated or the last fraction of radiotherapy has been administered within approximately 3 weeks prior to randomization.
• Brain metastases that are untreated, symptomatic, or require therapy to control symptoms or any radiation, surgery, or other therapy to control symptoms from brain metastases within 2 months prior to randomization.
• History of exposure to the following cumulative doses of anthracyclines: Doxorubicin or liposomal doxorubicin > 500 mg/m^2; epirubicin > 900 mg/m^2; mitoxantrone > 120mg/m^2 and idarubicin > 90 mg/m^2.
• Current unstable angina.
• History of symptomatic congestive heart failure, or ventricular arrhythmia requiring treatment.
• History of myocardial infarction within 6 months prior to randomization.
• Left ventricular ejection fraction (LVEF) below 50% within approximately 28 days prior to randomization.
• History of decreased LVEF or symptomatic congestive heart failure (CHF) with previous adjuvant trastuzumab treatment.
• Cardiac troponin I ≥ 0.2 ng/mL within 28 days of randomization.
• Severe dyspnea at rest because of complications of advanced malignancy or requiring current continuous oxygen therapy.
• Current severe, uncontrolled systemic disease (eg, clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures).
• Major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment.
• Current pregnancy or lactation.
• History of receiving any investigational treatment within approximately 28 days prior to randomization.
• Current known infection with human immunodeficiency virus (HIV), active hepatitis B and/or hepatitis C virus.
• History of intolerance (including Grade 3-4 infusion reaction) or hypersensitivity to trastuzumab, murine proteins, or docetaxel.
• Known hypersensitivity to any of the study drugs, including the excipients, or any drugs formulated in polysorbate 80.
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ellie Guardino, MD/PhD

Role: STUDY_DIRECTOR

Genentech, Inc.

References

Perez EA, Hurvitz SA, Amler LC, Mundt KE, Ng V, Guardino E, Gianni L. Relationship between HER2 expression and efficacy with first-line trastuzumab emtansine compared with trastuzumab plus docetaxel in TDM4450g: a randomized phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Breast Cancer Res. 2014 May 23;16(3):R50. doi: 10.1186/bcr3661.

Reference Type: DERIVED

PMID: 24887458 (View on PubMed)

Hurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, Guardino E, Song C, Tong B, Ng V, Chu YW, Perez EA. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2013 Mar 20;31(9):1157-63. doi: 10.1200/JCO.2012.44.9694. Epub 2013 Feb 4.

Reference Type: DERIVED

PMID: 23382472 (View on PubMed)

Other Identifiers

TDM4450g

Identifier Type: OTHER

Identifier Source: secondary_id

BO21976

Identifier Type: -

Identifier Source: org_study_id