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A Randomized, Multicenter, Phase ii Study of the Efficacy and Safety of 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


Phase 2
18 Years
N/A
Not Enrolling
Both
Breast Cancer

Thank you

Trial Information

A Randomized, Multicenter, Phase ii Study of the Efficacy and Safety of 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


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.

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free Survival (PFS) by the Investigator Using Modified Response Evaluation Criteria In Solid Tumors (RECIST)

Outcome Description:

PFS was defined as the time from randomization (R) to first documented investigator-assessed radiographic or clinical disease progression (PD) or death due to any cause, whichever occurred first. For target lesions (TL), PD was defined as at least a 20% increase in the sum of the longest diameter (SLD) of TLs, taking as reference the SLD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Data for patients without PD or death were censored at the last date of tumor assessment prior to crossover (or, if no tumor assessment was performed after Baseline, at the R date +1 day). Data for patients who were lost to follow-up were censored at the last date of tumor assessment prior to crossover at which the patient was known to be progression free. Data for patients with no post-baseline tumor assessment were censored at the R date +1 day.

Outcome Time Frame:

Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months)

Safety Issue:

No

Principal Investigator

Ellie Guardino, MD/PhD

Investigator Role:

Study Director

Investigator Affiliation:

Genentech

Authority:

United States: Food and Drug Administration

Study ID:

TDM4450g

NCT ID:

NCT00679341

Start Date:

September 2008

Completion Date:

May 2012

Related Keywords:

  • Breast Cancer
  • HER2-positive breast cancer
  • HER2
  • Herceptin
  • Taxotere
  • MBC
  • Breast cancer
  • TDM1
  • TDM-1
  • HER2-positive
  • HER2+
  • HER2 positive breast cancer
  • HER2+ breast cancer
  • Armed Herceptin
  • Trastuzumab emtansine
  • Trastuzumab DM1
  • Breast Neoplasms
  • Neoplasm Metastasis

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