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.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01419197
First received: August 16, 2011
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

This randomized, multicenter, 2-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 trastuzumab emtansine 3.6 mg/kg intravenously every 21 days or treatment of the physician's choice. Patients continue to receive study treatment 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
Drug: Treatment of physician's choice
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 [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ] [ Designated as safety issue: No ]
    Progression-free survival was defined as the time from randomization to the first documented disease progression by investigator assessment using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 or death from any cause, whichever occurred first.

  • Overall Survival [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from randomization to death from any cause.


Secondary Outcome Measures:
  • Percentage of Participants With an Objective Response [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ] [ Designated as safety issue: No ]
    An objective response was defined as a complete or partial response determined on 2 consecutive occasions ≥ 4 weeks apart using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must be < 10 mm on the short axis. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum. Participants who had no post-baseline tumor assessment were counted as non-responders.

  • Duration of the Objective Response [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ] [ Designated as safety issue: No ]
    Duration of the objective response was defined as the time from the first tumor assessment that was judged to indicate that the patient had an objective response to the time of first documented disease progression using RECIST v1.1 per investigator assessment or death from any cause, whichever occurred first.

  • 6-month and 1-year Survival [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ] [ Designated as safety issue: No ]
    6-month and 1-year survival were defined as the percentage of participants who were alive at 6 months and 1 year, respectively.

  • Time to Pain Symptom Progression [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ] [ Designated as safety issue: No ]
    Time to pain symptom progression was defined as the time from randomization to the first documentation of an increase in narcotic use and/or a 10 point increase from Baseline in the pain score as measured by the European Organisation for Research and Treatment of Cancer, Quality of Life Questionnaire for patients with bone metastases (EORTC QLQ-BM22). The EORTC QLQ-BM22 assesses the symptoms of bone metastases using 22 items: 5 items for sites of pain, 3 pain characteristics, 8 functional interference aspects, and 6 psychosocial aspects. The pain score was derived from the 3 pain characteristic items. Each item was rated on a 4-point scale, where 1=Not at all to 4=Very much. The pain score was the sum of the 3 pain characteristic scores and was normalized to a scale of 0 to 100. A higher score indicates greater pain.

  • Change From Baseline in the EORTC QLQ-BM22 Pain Score on Day 1 of Each Cycle [ Time Frame: Baseline to the clinical cut-off date of 11 Feb 2013 (up to 2 years) ] [ Designated as safety issue: No ]
    The EORTC QLQ-BM22 assesses the symptoms of bone metastases using 22 items: 5 items for sites of pain, 3 pain characteristics, 8 functional interference aspects, and 6 psychosocial aspects. The pain score was derived from the 3 pain characteristic items. Each item was rated on a 4-point scale, where 1=Not at all to 4=Very much. The pain score was the sum of the 3 pain characteristic scores and was normalized to a scale of 0 to 100. A higher score indicates greater pain. A negative change score indicates improvement.


Enrollment: 602
Study Start Date: February 2011
Estimated Study Completion Date: June 2015
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trastuzumab emtansine
Trastuzumab emtansine 3.6 mg/kg intravenously every 3 weeks until disease progression (as assessed by the investigator) or unmanageable toxicity.
Drug: Trastuzumab emtansine
The dose was calculated based on the patient's Baseline weight on Day 1 of each 3-week treatment cycle. The same dose was administered in subsequent cycles if the patient's weight stayed within 10% of the Baseline weight. If there was a weight change > 10%, the dose was adjusted accordingly and the recorded weight became the new Baseline weight. Trastuzumab emtansine was provided as a single-use lyophilized formulation.
Other Names:
  • Kadcyla
  • T-DM1
Active Comparator: Treatment of physician's choice
Treatment of physician's choice until disease progression (as assessed by the investigator) or unmanageable toxicity.
Drug: Treatment of physician's choice

The treatment of physician's choice (TPC) was a protocol-specified approved or standard of care therapy or combination of therapies, based on frequently used regimens for late-line HER2-positive metastatic breast cancer treatment after receipt of both trastuzumab- and lapatinib-containing regimens. The therapies included single-agent chemotherapy, single-agent (eg, tamoxifen or aromatase inhibitor) or dual-agent (eg, aromatase inhibitor with luteinizing hormone releasing hormone [LHRH] agonist) hormonal therapy for hormone receptor positive-disease, and HER2-directed therapy.

Participants who had documented progressive disease (PD) were eligible to cross over to receive trastuzumab emtansine 3.6 mg/kg. Patients who crossed over remained on trastuzumab emtansine treatment until another PD event or unmanageable toxicity.

The formulation, storage, and preparation of all TPC were as per the appropriate package insert or national prescribing information.


  Eligibility

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

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.
  • Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram or multi gated acquisition scan.

Exclusion Criteria:

  • Chemotherapy ≤ 21 days before first study treatment.
  • Trastuzumab ≤ 21 days before first study treatment.
  • Lapatinib ≤ 14 days before first study treatment.
  • Prior enrollment in a trastuzumab emtansine containing study, regardless whether the patient received prior trastuzumab emtansine.
  • 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
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: NCT01419197

  Show 184 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Abraham C.F. Leung, MD Genentech, Inc.
  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
Results First Received: February 7, 2014
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 22, 2014