A Study of Trastuzumab Emtansine in Participants With Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer Who Have Received Prior Anti-HER2 And Chemotherapy-based Treatment

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01702571
First received: October 4, 2012
Last updated: August 17, 2016
Last verified: August 2016
  Purpose
This two-cohort, open-label, multicenter study will assess the safety, efficacy and tolerability of trastuzumab emtansine in participants with HER2-positive locally advanced breast cancer (LABC) or metastatic breast cancer (mBC) who have received prior anti-HER2 and chemotherapy-based treatment. Participants in Cohort 1 will be drawn from the general participant population; Cohort 2 will include only Asian participants.

Condition Intervention Phase
Breast Cancer
Drug: Trastuzumab Emtansine
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Two-Cohort, Open-Label, Multicenter Study of Trastuzumab Emtansine (T-DM1) in HER2-Positive Locally Advanced or Metastatic Breast Cancer Patients Who Have Received Prior Anti-HER2 and Chemotherapy-Based Treatment

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 6 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-Free Survival According to Response Evaluation for Solid Tumors (RECIST) Version (v) 1.1 As Per Investigator Assessment [ Time Frame: Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 6 years) ] [ Designated as safety issue: No ]
  • Overall Survival According to RECIST v 1.1 As Per Investigator Assessment [ Time Frame: Baseline until death (Up to approximately 6 years) ] [ Designated as safety issue: No ]
  • Percentage of Participants with Best Overall Response (Complete Response [CR] or Partial Response [PR]) According to RECIST v 1.1 As Per Investigator Assessment [ Time Frame: Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 6 years) ] [ Designated as safety issue: No ]
  • Percentage of Participants with Clinical Benefit (CR or PR or Stable Disease [SD]) According to RECIST v 1.1 [ Time Frame: Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 6 years) ] [ Designated as safety issue: No ]
  • Duration of Response According to RECIST v 1.1 [ Time Frame: Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 6 years) ] [ Designated as safety issue: No ]
  • Time to Response According to RECIST v 1.1 [ Time Frame: Baseline up to disease progression or death due to any cause, whichever occurs first (assessed every 12 weeks during treatment period thereafter 28-42 days after the last dose or every 3-6 months up to approximately 6 years) ] [ Designated as safety issue: No ]

Estimated Enrollment: 2220
Study Start Date: November 2012
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trastuzumab Emtansine (All Participants)
This cohort will enroll all participants with HER2 positive, unresectable, LABC or mBC who have previously received prior anti-HER2 and chemotherapy treatment and have progressed on or after the most recent treatment for LABC or mBC, or within 6 months of completing adjuvant therapy. Participants will receive trastuzumab emtansine every 3 weeks until unacceptable toxicity, withdrawal of consent, or disease progression.
Drug: Trastuzumab Emtansine
Participants will receive trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) intravenously on Day 1 of a 3-week cycle every 3 weeks until unacceptable toxicity, withdrawal of consent, or disease progression.
Other Name: RO5304020, Kadcyla
Experimental: Trastuzumab Emtansine (Asian Participants)
This cohort will enroll Asian race participants with HER2 positive, unresectable, LABC or mBC who have previously received prior anti-HER2 and chemotherapy treatment and have progressed on or after the most recent treatment for LABC or mBC, or within 6 months of completing adjuvant therapy. Participants will receive trastuzumab emtansine every 3 weeks until unacceptable toxicity, withdrawal of consent, or disease progression.
Drug: Trastuzumab Emtansine
Participants will receive trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) intravenously on Day 1 of a 3-week cycle every 3 weeks until unacceptable toxicity, withdrawal of consent, or disease progression.
Other Name: RO5304020, Kadcyla

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HER2-positive disease determined locally
  • Histologically or cytologically confirmed invasive breast cancer
  • Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced or metastatic setting must include both chemotherapy, alone or in combination with another agent, and an anti-HER2 agent, alone or in combination with another agent
  • Documented progression of incurable, unresectable, LABC, or mBC, defined by the investigator: progression must occur during or after most recent treatment for LABC/mBC or within 6 months of completing adjuvant therapy
  • Measurable and/or non-measurable disease
  • Left ventricular ejection fraction (LVEF) >/=50% by either echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2
  • Adequate organ function
  • Use of highly effective contraception as defined by the protocol

Exclusion Criteria:

  • History of treatment with trastuzumab emtansine
  • Prior enrollment into a clinical study containing trastuzumab emtansine regardless of having received trastuzumab emtansine or not
  • Peripheral neuropathy of Grade >/= 3 per National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) v 4.0
  • History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, synchronous or previously diagnosed HER2-positive breast cancer
  • History of receiving any anti-cancer drug/biologic or investigational treatment within 21 days prior to first study treatment except hormone therapy, which can be given up to 7 days prior to first study treatment; recovery of treatment-related toxicity consistent with other eligibility criteria
  • History of exposure to cumulative doses of anthracyclines
  • History of radiation therapy within 14 days of first study treatment. The participant must have recovered from any resulting acute toxicity (to Grade </=1) prior to first study treatment.
  • Metastatic central nervous system (CNS) disease only
  • Brain metastases which are symptomatic
  • History of a decrease in LVEF to less than (<) 40% or symptomatic congestive heart failure (CHF) with previous trastuzumab treatment
  • History of symptomatic CHF (New York Heart Association [NYHA] Classes II-IV) or serious cardiac arrhythmia requiring treatment
  • History of myocardial infarction or unstable angina within 6 months of first study treatment
  • Current dyspnea at rest due to complications of advanced malignancy or requirement for continuous oxygen therapy
  • Current severe, uncontrolled systemic disease (clinically significant cardiovascular, pulmonary, or metabolic disease)
  • Pregnancy or lactation
  • Currently known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
  • History of intolerance (such as Grade 3-4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins or any component of the product
  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: NCT01702571

Contacts
Contact: Reference Study ID Number: MO28231 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

  Show 301 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01702571     History of Changes
Other Study ID Numbers: MO28231  2012-001628-37 
Study First Received: October 4, 2012
Last Updated: August 17, 2016
Health Authority: France: Agence nationale de securité du médicament et des produits de santé (ANSM)

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Ado-trastuzumab emtansine
Trastuzumab
Maytansine
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 23, 2016