ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Trastuzumab Emtansine (Trastuzumab-MCC-DM1, T-DM1) in Combination With Pertuzumab Administered to Patients With Human Epidermal Growth Factor Receptor-2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer Who Have Previously Received Trastuzumab

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00875979
Recruitment Status : Completed
First Posted : April 6, 2009
Results First Posted : July 18, 2013
Last Update Posted : December 24, 2013
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Hoffmann-La Roche

April 2, 2009
April 6, 2009
February 22, 2013
July 18, 2013
December 24, 2013
May 2009
August 2011   (Final data collection date for primary outcome measure)
Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Baseline through the end of the study (up to 2 years 3 months) ]
A patient had an objective response if they had a complete response or a partial response on 2 consecutive occasions ≥ 4 weeks apart. For target lesions, a complete response was defined as the disappearance of all target lesions; a partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. For non-target lesions, a complete response was defined as the disappearance of all non-target lesions; a partial response was defined as the persistence of 1 or more non-target lesions.
  • 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 and/or pertuzumab [ Time Frame: Up to study discontinuation or up to 1 year after the last patient is enrolled ]
  • Change in cardiac function [ Time Frame: Up to study discontinuation or up to 1 year after the last patient is enrolled ]
  • Incidence, nature, and severity of adverse events [ Time Frame: Up to study discontinuation or up to 1 year after the last patient is enrolled ]
  • Objective response rate based on investigator assessment [ Time Frame: Up to 1 year after the last patient is enrolled ]
  • Pharmacokinetic and pharmacodynamic parameters of both T-DM1 and pertuzumab [ Time Frame: Up to study discontinuation or up to 1 year after the last patient is enrolled ]
Complete list of historical versions of study NCT00875979 on ClinicalTrials.gov Archive Site
  • Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Baseline through the end of the study (up to 2 years 3 months) ]
    Duration of objective response was defined as the time from initial response to disease progression (PD) or death from any cause. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Target lesions should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions.
  • Progression-free Survival Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Baseline through the end of the study (up to 2 years 3 months) ]
    Progression-free survival was defined as the time from randomization to first documented disease progression (PD) or death due to any cause within 30 days of the last treatment, whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Target lesions should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions.
  • Progression-free survival [ Time Frame: Censoring at time of last tumor assessment ]
  • Duration of response [ Time Frame: Censoring at time of last tumor assessment ]
Not Provided
Not Provided
 
A Study of Trastuzumab Emtansine (Trastuzumab-MCC-DM1, T-DM1) in Combination With Pertuzumab Administered to Patients With Human Epidermal Growth Factor Receptor-2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer Who Have Previously Received Trastuzumab
A Phase Ib/II, Open-label Study of the Safety, Tolerability, and Efficacy of Trastuzumab Emtansine (Trastuzumab-MCC-DM1, T-DM1) in Combination With Pertuzumab Administered Intravenously to Patients With Human Epidermal Growth Factor Receptor-2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer Who Have Previously Received Trastuzumab
This was a multi-institutional, multinational, open-label, single-arm Phase Ib/II study designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of trastuzumab emtansine (trastuzumab-MCC-DM1) administered by intravenous (IV) infusion in combination with pertuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive locally advanced or metastatic breast cancer who had previously received trastuzumab.
There were 2 phases in the study, a Dose Escalation phase (Phase 1b) and a Dose Expansion phase (Phase 2a). In the Dose Escalation phase, 3 patients were enrolled at the first dose level (3.0 mg/kg trastuzumab emtansine) and and 6 patients were enrolled at the second dose level (3.6 mg/kg trastuzumab emtansine). An additional 58 patients were enrolled at the 3.6 mg/kg trastuzumab emtansine dose level in the Dose Expansion phase (Phase 2a) of the study.
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Metastatic Breast Cancer
  • Drug: Trastuzumab emtansine [Kadcyla] 3.0 mg/kg
    Trastuzumab emtansine was provided as a single-use lyophilized formulation.
    Other Names:
    • trastuzumab-DM1
    • trastuzumab-MCC-DM1
    • T-DM1
  • Drug: Trastuzumab emtansine [Kadcyla] 3.6 mg/kg
    Trastuzumab emtansine was provided as a single-use lyophilized formulation.
    Other Names:
    • trastuzumab-DM1
    • trastuzumab-MCC-DM1
    • T-DM1
  • Drug: Pertuzumab 420 mg
    Pertuzumab was provided as a single-use formulation.
    Other Name: Perjeta
  • Experimental: Trastuzumab emtansine 3.0 mg/kg + pertuzumab 420 mg
    Patients received trastuzumab emtansine 3.0 mg/kg intravenously (IV) on Day 1 of every 3 week cycle until progressive disease, intolerable toxicity, initiation of another anti-cancer therapy, or patient discontinuation. Patients also received a loading dose of 840 mg of pertuzumab IV on Day 1 of Cycle 1 followed by pertuzumab 420 mg IV on Day 1 of every subsequent 3 week cycle.
    Interventions:
    • Drug: Trastuzumab emtansine [Kadcyla] 3.0 mg/kg
    • Drug: Pertuzumab 420 mg
  • Experimental: Trastuzumab emtansine 3.6 mg/kg + pertuzumab 420 mg
    Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) on Day 1 of every 3 week cycle until progressive disease, intolerable toxicity, initiation of another anti-cancer therapy, or patient discontinuation. Patients also received a loading dose of 840 mg of pertuzumab IV on Day 1 of Cycle 1 followed by pertuzumab 420 mg IV on Day 1 of every subsequent 3 week cycle.
    Interventions:
    • Drug: Trastuzumab emtansine [Kadcyla] 3.6 mg/kg
    • Drug: Pertuzumab 420 mg
Miller KD, Diéras V, Harbeck N, Andre F, Mahtani RL, Gianni L, Albain KS, Crivellari D, Fang L, Michelson G, de Haas SL, Burris HA. Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2-positive, locally advanced, or metastatic breast cancer. J Clin Oncol. 2014 May 10;32(14):1437-44. doi: 10.1200/JCO.2013.52.6590. Epub 2014 Apr 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
67
40
August 2011
August 2011   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically documented human epidermal growth factor receptor 2 (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.
  • No prior trastuzumab emtansine (T-DM1) or pertuzumab therapy.
  • Measurable disease.
  • For women of childbearing potential, agreement to use an effective form of contraception and to continue its use for the duration of the study.
  • Life expectancy ≥ 90 days.

Exclusion Criteria:

  • Less 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; palliative radiation therapy involving ≤ 25% of marrow-bearing bone if administered ≥ 14 days prior to first study treatment.
  • History of intolerance or hypersensitivity to trastuzumab and/or adverse events related to trastuzumab that resulted in trastuzumab being permanently discontinued.
  • Peripheral neuropathy of Grade ≥ 2.
  • History of clinically significant cardiac dysfunction.
  • Current severe, uncontrolled systemic disease, eg, clinically significant cardiovascular, pulmonary, or metabolic disease.
  • Brain metastases that are untreated, progressive, or have required any type of therapy to control symptoms from brain metastases within 60 days of the first study treatment.
  • History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Belgium,   Canada,   France,   Germany,   Italy,   Spain,   United States
 
 
NCT00875979
BO22495
TDM4373g ( Other Identifier: Genentech )
Not Provided
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Roche Pharma AG
Study Director: Elaine K. Wong, M.Sc., M.D. Genentech, Inc.
Hoffmann-La Roche
December 2013

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