A Study of Trastuzumab Emtansine, Paclitaxel, and Pertuzumab in Patients With HER2-Positive, Locally Advanced or Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00951665
First received: August 3, 2009
Last updated: October 6, 2014
Last verified: October 2014

August 3, 2009
October 6, 2014
August 2009
February 2012   (final data collection date for primary 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 [ Time Frame: Through study discontinuation or 12 months of study treatment, whichever occurs first ] [ Designated as safety issue: No ]
  • Frequency and nature of dose limiting toxicities (DLTs) and highest tolerable doses of trastuzumab emtansine and paclitaxel when given in combination [ Time Frame: Through study discontinuation or 12 months of study treatment, whichever occurs first ] [ Designated as safety issue: No ]
  • Incidence, nature, and severity of adverse events and serious adverse events [ Time Frame: Through study discontinuation or 12 months of study treatment, whichever occurs first ] [ Designated as safety issue: No ]
  • Pharmacokinetics of trastuzumab emtansine in the presence of paclitaxel, and of paclitaxel in the presence and absence of trastuzumab emtansine [ Time Frame: Through study discontinuation or 12 months of study treatment, whichever occurs first ] [ Designated as safety issue: No ]
  • Phase IIa: Proportion of patients who receive paclitaxel weekly x 12 doses in combination with trastuzumab emtansine (with or without pertuzumab) [ Time Frame: Through study discontinuation or 12 months of study treatment, whichever occurs first ] [ Designated as safety issue: No ]
  • 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 T-DM1, paclitaxel, and/or pertuzumab [ Time Frame: Through study discontinuation or 12 months of study treatment, whichever occurs first ]
  • Frequency and nature of dose limiting toxicities (DLTs) and highest tolerable doses of T-DM1 and paclitaxel when given in combination [ Time Frame: Through study discontinuation or 12 months of study treatment, whichever occurs first ]
  • Incidence, nature, and severity of adverse events and serious adverse events [ Time Frame: Through study discontinuation or 12 months of study treatment, whichever occurs first ]
  • Pharmacokinetics of T-DM1 in the presence of paclitaxel, and of paclitaxel in the presence and absence of T-DM1 [ Time Frame: Through study discontinuation or 12 months of study treatment, whichever occurs first ]
Complete list of historical versions of study NCT00951665 on ClinicalTrials.gov Archive Site
  • Objective response rate based on investigator assessment [ Time Frame: Through study discontinuation or 12 months of study treatment, whichever occurs first ] [ Designated as safety issue: No ]
  • Progression-free survival, duration of response and clinical benefit rate [ Time Frame: Through study discontinuation or 12 months of study treatment, whichever occurs first ] [ Designated as safety issue: No ]
  • Objective response rate based on investigator assessment [ Time Frame: Through study discontinuation or 12 months of study treatment, whichever occurs first ]
  • Progression-free survival, duration of response and clinical benefit rate [ Time Frame: Through study discontinuation or 12 months of study treatment, whichever occurs first ]
Not Provided
Not Provided
 
A Study of Trastuzumab Emtansine, Paclitaxel, and Pertuzumab in Patients With HER2-Positive, Locally Advanced or Metastatic Breast Cancer
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

This Phase Ib-IIa, multi-institutional, open-label, dose-escalation study is des igned to evaluate the safety, tolerability, pharmacokinetics and feasibility of trastuzumab emtansine (T-DM1) administered by intravenous (IV) infusion in combi nation with paclitaxel (and pertuzumab, if applicable) in patients with HER2-pos itive, locally advanced or metastatic breast cancer.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Metastatic Breast Cancer
  • Drug: paclitaxel
    Intravenous repeating dose
  • Drug: pertuzumab [Perjeta]
    Intravenous repeating dose
  • Drug: trastuzumab emtansine [Kadcyla]
    Intravenous escalating dose
Experimental: 1
Interventions:
  • Drug: paclitaxel
  • Drug: pertuzumab [Perjeta]
  • Drug: trastuzumab emtansine [Kadcyla]
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
107
June 2013
February 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00951665
TDM4652g, GO01355
Not Provided
Genentech, Inc.
Genentech, Inc.
Not Provided
Study Director: Jane Huang, M.D. Genentech, Inc.
Genentech, Inc.
October 2014

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