A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician's Choice in Patients With HER2-Positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-Directed Therapy (TH3RESA)

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
First received: August 16, 2011
Last updated: January 6, 2014
Last verified: January 2014

This randomized, multicenter, two-arm, open-label study (TH3RESA) will evaluate the efficacy and safety of trastuzumab emtansine (T-DM1) in comparison with treatment of the physician's choice in patients with metastatic or unresectable locally advanced/recurrent HER2-positive breast cancer. Eligible patients will be randomized to receive either T-DM1 3.6 mg/kg intravenously every 21 days or treatment of the physician's choice. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. This study is also known under Roche study protocol number BO25734.

Condition Intervention Phase
Breast Cancer
Drug: trastuzumab emtansine [Kadcyla]
Drug: anti-cancer therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Multicenter, Two-Arm, Open-Label Trial to Evaluate the Efficacy of Trastuzumab Emtansine Compared With Treatment of Physician's Choice in Patients With HER2 Positive Metastatic Breast Cancer Who Have Received at Least Two Prior Regimens of HER2 Directed Therapy

Resource links provided by NLM:

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Progression-free survival by investigator assessment according to RECIST [ Time Frame: approximately 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: approximately 3.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response rate [ Time Frame: approximately 3.5 years ] [ Designated as safety issue: No ]
  • Duration of objective response (DOR) [ Time Frame: approximately 3.5 years ] [ Designated as safety issue: No ]
  • Land mark survival rate (6 months/1 year) [ Time Frame: approximately 3.5 years ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events [ Time Frame: approximately 3.5 years ] [ Designated as safety issue: No ]
  • Time to pain symptom progression as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire BM22 [ Time Frame: approximately 3.5 years ] [ Designated as safety issue: No ]
  • Global Health Status/Quality of Life as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 [ Time Frame: approximately 3.5 years ] [ Designated as safety issue: No ]
  • Global Health Status as measured by Euro-Qol 5D [ Time Frame: approximately 3.5 years ] [ Designated as safety issue: No ]
  • Pharmacokinetics: serum concentration of trastuzumab emtansine [ Time Frame: approximately 3.5 years ] [ Designated as safety issue: No ]
  • Pharmacokinetics: plasma concentration of DM1 [ Time Frame: approximately 3.5 years ] [ Designated as safety issue: No ]

Enrollment: 604
Study Start Date: September 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: trastuzumab emtansine [Kadcyla]
3.6 mg/ kg intravenously every 21 days
Active Comparator: B
Drug: anti-cancer therapy
Drug: anti-cancer therapy
Treatment of physician's choice (chemotherapy, hormonal therapy, biologic drug and/or HER2-directed therapy)


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

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Histologically or cytologically documented breast cancer
  • Metastatic or unresectable locally advanced/recurrent breast cancer
  • HER2-positive disease by prospective laboratory confirmation
  • Disease progression on the last regimen received as defined by the investigator
  • Prior treatment with an trastuzumab, a taxane, and lapatinib
  • Disease progression after at least two regimens of HER2-directed therapy in the metastatic or unresectable locally advanced/recurrent setting
  • Adequate organ function, as evidenced by laboratory results
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • LVEF >/= 50% by ECHO or MUGA

Exclusion Criteria:

  • Chemotherapy </= 21 days before first study treatment
  • Trastuzumab </= 21 days before first study treatment
  • Lapatinib </= 14 days before first study treatment
  • Prior enrolment in a T-DM1 containing study, regardless whether the patient received prior T-DM1
  • Brain metastases that are untreated or symptomatic, or require any radiation, surgery or corticosteroid therapy to control symptoms within 1 month of randomization
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01419197

  Show 184 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Study Director: Melanie Smitt, M.D. Genentech
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01419197     History of Changes
Other Study ID Numbers: TDM4997g, BO25734, 2011-000509-29
Study First Received: August 16, 2011
Last Updated: January 6, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on April 17, 2014