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
ClinicalTrials.gov Identifier:
NCT00951665
First received: August 3, 2009
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Metastatic Breast Cancer
Drug: paclitaxel
Drug: pertuzumab [Perjeta]
Drug: trastuzumab emtansine [Kadcyla]
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Genentech:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 107
Study Start Date: August 2009
Study Completion Date: June 2013
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: paclitaxel
Intravenous repeating dose
Drug: pertuzumab [Perjeta]
Intravenous repeating dose
Drug: trastuzumab emtansine [Kadcyla]
Intravenous escalating dose

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00951665

Locations
United States, California
Stanford, California, United States, 94305-5456
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Massachusetts
Boston, Massachusetts, United States, 02115
United States, Michigan
Detroit, Michigan, United States, 48201
United States, New York
New York, New York, United States, 10065
Sponsors and Collaborators
Genentech
Investigators
Study Director: Jane Huang, M.D. Genentech
  More Information

No publications provided

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT00951665     History of Changes
Other Study ID Numbers: TDM4652g, GO01355
Study First Received: August 3, 2009
Last Updated: July 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Genentech:
TDM-1
TDM1
Trastuzumab DM1
Trastuzumab emtansine
Armed Herceptin
HER2
HER2+
HER2 Positive Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Maytansine
Trastuzumab
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014