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A Phase Ib-IIa, Open-label, Dose-Escalation Study of the Safety, Tolerability and Pharmacokinetics of Trastuzumab Emtansine, Paclitaxel and Pertuzumab Administered Intravenously to Patients With Her2-positive, Locally Advanced or Metastatic Breast Cancer


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Metastatic Breast Cancer

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Trial Information

A Phase Ib-IIa, Open-label, Dose-Escalation Study of the Safety, Tolerability and Pharmacokinetics of Trastuzumab Emtansine, Paclitaxel and Pertuzumab Administered Intravenously to Patients With Her2-positive, Locally Advanced or Metastatic Breast Cancer


Inclusion Criteria:



- Histologically documented HER2-positive locally advanced or metastatic breast cancer

- Tumor tissue blocks or 15-20 unstained tissue slides for confirmatory central
laboratory HER2 status testing and other exploratory assessments

- Prior trastuzumab in any line of therapy (Phase Ib patients only)

- No prior trastuzumab emtansine (T-DM1) or pertuzumab therapy

- Measurable or evaluable disease

- Cardiac ejection fraction >=50% by either ECHO or MUGA scan

- Life expectancy >= 90 days as assessed by the investigator

Exclusion Criteria:

- Fewer than 21 days since the last anti-tumor therapy, including chemotherapy,
biologic, experimental, immune, hormonal or radiotherapy for the treatment of breast
cancer, with the following exceptions: hormone-replacement therapy or oral
contraceptives are allowed; palliative radiation therapy involving <=25% of
marrow-bearing bone is allowed if completed within >= 14 days prior to first study
treatment

- History of intolerance or hypersensitivity to trastuzumab and/or adverse events
related to trastuzumab, murine proteins, or any of the excipients that resulted in
trastuzumab being permanently discontinued

- Peripheral neuropathy of Grade >= 2 per NCI CTCAE, Version 3.0, at the time of, or
within 3 weeks prior to, the first study therapy (Phase Ib patients)

- Peripheral neuropathy of Grade >/=1 per NCI CTCAE, Version 3.0, at the time of, or
within 3 weeks prior to, the first study therapy (Phase IIa patients)

- History of exposure to the following cumulative doses of anthracyclines: Doxorubicin
> 500 mg/m^2; Liposomal doxorubicin > 900 mg/m^2; Epirubicin > 720 mg/m^2

- History of clinically significant cardiac dysfunction

- Brain metastases that are untreated, or progressive, or have required any type of
therapy (including radiation, surgery, or steroids) to control symptoms from brain
metastases within 60 days prior to the first study treatment.

- History of other malignancy within the last 5 years, except for appropriately treated
carcinoma in situ of the cervix, basal cell carcinoma, or synchronous or subsequent
HER2-positive breast cancer or other malignancy with a similar expected curative
outcome

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Adverse events or changes in physical findings and clinical laboratory results during and following study drug administration that result in dose modification, dose delay, or discontinuation of trastuzumab emtansine, paclitaxel, and/or pertuzumab

Outcome Time Frame:

Through study discontinuation or 12 months of study treatment, whichever occurs first

Safety Issue:

No

Principal Investigator

Jane Huang, M.D.

Investigator Role:

Study Director

Investigator Affiliation:

Genentech

Authority:

United States: Food and Drug Administration

Study ID:

TDM4652g

NCT ID:

NCT00951665

Start Date:

August 2009

Completion Date:

December 2013

Related Keywords:

  • Metastatic Breast Cancer
  • TDM-1
  • TDM1
  • Trastuzumab DM1
  • Trastuzumab emtansine
  • Armed Herceptin
  • HER2
  • HER2+
  • HER2 Positive Breast Cancer
  • Breast Neoplasms

Name

Location

Fountain Valley, California  92708
Albany, New York  12208
Flint, Michigan  48532
Denver, Colorado  
Boston, Massachusetts