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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

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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

Tracking Information
First Submitted Date  ICMJE April 2, 2009
First Posted Date  ICMJE April 6, 2009
Results First Submitted Date  ICMJE February 22, 2013
Results First Posted Date  ICMJE July 18, 2013
Last Update Posted Date December 24, 2013
Study Start Date  ICMJE May 2009
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 13, 2013)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 2, 2009)
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 13, 2013)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2009)
  • Progression-free survival [ Time Frame: Censoring at time of last tumor assessment ]
  • Duration of response [ Time Frame: Censoring at time of last tumor assessment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Breast Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications * 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.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 13, 2013)
67
Original Estimated Enrollment  ICMJE
 (submitted: April 2, 2009)
40
Actual Study Completion Date  ICMJE August 2011
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   France,   Germany,   Italy,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00875979
Other Study ID Numbers  ICMJE BO22495
TDM4373g ( Other Identifier: Genentech )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Roche Pharma AG
Investigators  ICMJE
Study Director: Elaine K. Wong, M.Sc., M.D. Genentech, Inc.
PRS Account Hoffmann-La Roche
Verification Date December 2013

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