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Phase II Trial to Compare the Safety of Two Chemotherapy Plus Trastuzumab Regimens as Adjuvant Therapy for HER2-positive Breast Cancer (Study P05048)

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ClinicalTrials.gov Identifier: NCT00550771
Recruitment Status : Completed
First Posted : October 30, 2007
Results First Posted : October 3, 2011
Last Update Posted : June 7, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE October 29, 2007
First Posted Date  ICMJE October 30, 2007
Results First Submitted Date  ICMJE August 26, 2011
Results First Posted Date  ICMJE October 3, 2011
Last Update Posted Date June 7, 2017
Actual Study Start Date  ICMJE July 16, 2007
Actual Primary Completion Date August 23, 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 26, 2011)
Number of Participants Who Experienced Cardiac Events (Level 1 or 2), or Inability to Administer Trastuzumab Either During the 8 Cycles of Chemotherapy or According to Package Insert for a Total Duration of 1 Year [ Time Frame: 8 cycles of chemotherapy and subsequently one year of planned trastuzumab treatment ]
Cardiac events defined as: Level 1: Cardiac death due to heart failure (HF), myocardial infarction or arrhythmia, or probable cardiac death defined as sudden, unexpected death within 24 hours of a definite or probable cardiac event, or severe symptomatic HF, concomitant with a left ventricular ejection fraction (LVEF) drop of >10 percentage points from baseline and to ≤50% LVEF Level 2: Asymptomatic systolic dysfunction or mildly symptomatic HF concomitant with an LVEF drop of >10 percentage points from baseline and to <50% LVEF; the LVEF drop was to have been confirmed within 3-4 weeks.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00550771 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 26, 2011)
  • Number of Participants Who Experienced Cardiac Events (Level 1 or 2) or Inability to Administer Trastuzumab During the 8 Cycles of Chemotherapy [ Time Frame: During the 8 courses of chemotherapy ]
    Cardiac events defined as: Level 1: Cardiac death due to heart failure (HF), myocardial infarction or arrhythmia, or probable cardiac death defined as sudden, unexpected death within 24 hours of a definite or probable cardiac event, or severe symptomatic HF, concomitant with a left ventricular ejection fraction (LVEF) drop of >10 percentage points from baseline and to ≤50% LVEF Level 2: Asymptomatic systolic dysfunction or mildly symptomatic HF concomitant with an LVEF drop of >10 percentage points from baseline and to <50% LVEF; the LVEF drop was to have been confirmed within 3-4 weeks.
  • Number of Participants Who Experienced Cardiac Events (Level 1 or 2) or Inability to Administer Trastuzumab During 1 Year of Trastuzumab Therapy [ Time Frame: During 1 year of trastuzumab therapy ]
    Cardiac events defined as: Level 1: Cardiac death due to heart failure (HF), myocardial infarction or arrhythmia, or probable cardiac death defined as sudden, unexpected death within 24 hours of a definite or probable cardiac event, or severe symptomatic HF, concomitant with a left ventricular ejection fraction (LVEF) drop of >10 percentage points from baseline and to ≤50% LVEF Level 2: Asymptomatic systolic dysfunction or mildly symptomatic HF concomitant with an LVEF drop of >10 percentage points from baseline and to <50% LVEF; the LVEF drop was to have been confirmed within 3-4 weeks.
  • Number of Participants Who Survived Without Relapse [ Time Frame: Approximately 2 years ]
    Relapse-free survival would have been determined by Kaplan-Meier method. This was not calculated, since the 2 year follow-up was curtailed.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Trial to Compare the Safety of Two Chemotherapy Plus Trastuzumab Regimens as Adjuvant Therapy for HER2-positive Breast Cancer (Study P05048)
Official Title  ICMJE Randomized Phase II Multinational Trial to Evaluate the Safety of Two Chemotherapy Plus Trastuzumab Regimens as Adjuvant Therapy in Patients With HER2-positive Breast Cancer: Caelyx + Cyclophosphamide + Trastuzumab (C+C+H) or Doxorubicin + Cyclophosphamide (A+C), Each Followed by Paclitaxel + Trastuzumab (T+H) BACH
Brief Summary The purpose of this study is to compare the incidence of cardiac dysfunction in subjects with human epidermal growth factor receptor 2 (HER2) positive breast cancer treated with either doxorubicin or pegylated liposomal doxorubicin (PLD), both in combination with trastuzumab.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Neoplasm
Intervention  ICMJE
  • Drug: doxorubicin, cyclophosphamide, paclitaxel, trastuzumab
    doxorubicin 60 mg/m^2 IV push + cyclophosphamide 600 mg/m^2 IV over 30-90 minutes given every 21 days for 4 courses (12 weeks) followed by Paclitaxel 80 mg/m^2 IV over 60 minutes with trastuzumab 2 mg/kg IV over 30 minutes (first administration 4 mg/kg IV over 90 minutes) given weekly for 12 weeks (4 courses)
  • Drug: PLD, cyclophosphamide, trastuzumab, paclitaxel
    PLD 35 mg/m^2 IV over 60 minutes + cyclophosphamide 600 mg/m^2 IV over 30-90 minutes given every 21 days + trastuzumab 2 mg/kg IV over 30 minutes (first dose 4 mg/kg IV over 90 minutes) given once weekly for 4 courses (12 weeks) followed by Paclitaxel 80 mg/m^2 IV over 60 minutes with trastuzumab 2 mg/kg IV over 30 minutes given weekly for 12 weeks (4 courses)
    Other Name: pegylated liposomal doxorubicin (SCH 200746)
Study Arms  ICMJE
  • Active Comparator: Doxorubicin Based Regimen
    Intervention: Drug: doxorubicin, cyclophosphamide, paclitaxel, trastuzumab
  • Experimental: Pegylated Liposomal Doxorubicin (PLD) Based Regimen
    Intervention: Drug: PLD, cyclophosphamide, trastuzumab, paclitaxel
Publications * Rayson D, Suter TM, Jackisch C, van der Vegt S, Bermejo B, van den Bosch J, Vivanco GL, van Gent AM, Wildiers H, Torres A, Provencher L, Temizkan M, Chirgwin J, Canon JL, Ferrandina G, Srinivasan S, Zhang L, Richel DJ. Cardiac safety of adjuvant pegylated liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial. Ann Oncol. 2012 Jul;23(7):1780-8. doi: 10.1093/annonc/mdr519. Epub 2011 Nov 4.

*   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 23, 2009)
181
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE August 23, 2010
Actual Primary Completion Date August 23, 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Subjects with operable, node-positive or high-risk node-negative (see #3 below) HER2-positive breast carcinoma are eligible for the study, provided they satisfy the following criteria.

    • Subjects must demonstrate willingness to and be able to participate in the study and to adhere to dose and visit schedules
    • Subjects must be of female gender and >= 18 years of age
    • Subjects must have been diagnosed with operable, histologically confirmed adenocarcinoma of the breast with no clinical or radiological evidence of metastatic disease but with otherwise high or intermediate risk tumor characteristics:

      • node-positive: T1-3, N1-2, M0 (level of T [tumor involvement], N [lymph node involvement], & M [matastases]) OR
      • node-negative AND at least one of the following features:

        • Tumor >2 cm or
        • Tumor >1 cm and

          • Negative estrogen receptor/progesterone receptor (ER/PR) or
          • Malignancy Grade 2-3 or
          • Presence of peritumoral vascular invasion or
          • Age <35 years
    • HER2-positive by fluorescence in situ hybridization (FISH)(with gene amplification) or 3+ using

immunohistochemistry

  • Subjects must have had complete resection (R0) of the primary tumor and axillary lymph nodes (or must have negative sentinel node[s])
  • Baseline left ventricular ejection fraction (LVEF) by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) >=55%
  • Easter Cooperative Oncology Group (ECOG)-performance status of 0-1
  • Adequate postoperative bone marrow function with neutrophils >=1.5 x 10^9/l, platelets >=100 x 10^9/l and hemoglobin >= lower limit of normal (LLN)
  • Adequate renal function: calculated creatinine clearance >=50 ml/min
  • Adequate postoperative liver function with a total bilirubin < upper limit of normal (ULN), alkaline phosphatase <2.5 times the ULN and aspartate aminotransferase (AST) <1.5 times the ULN
  • Subjects must be free of any clinically relevant disease that would, in the principal investigator's and/or sponsor's opinion, interfere with the conduct of the study or study evaluations
  • Subjects of childbearing potential (including women who are less than one year postmenopausal and will be sexually active during the study) must agree to use a medically accepted method of contraception, while receiving protocol-specified medication and for 30 days (or as per local requirements) after stopping the medication or be surgically sterilized prior to screening
  • Subjects must be able to provide written informed consent

Exclusion Criteria:

  • Subject who meets any of the following exclusion criteria will be disqualified from participation in the study:

    • Clinical or radiological evidence of metastatic disease
    • Prior radiotherapy, chemotherapy or biotherapy for the currently diagnosed breast cancer prior to randomization
    • Clinically significant pericardial effusion
    • Serious cardiac illness including, but not confined to

      • history of documented congestive heart failure
      • history of any form of cardiomyopathy or active treatment for any form of cardiomyopathy
      • history of angina pectoris or documented transmural myocardial infarction, or active angina pectoris requiring medication
      • serious ventricular arrhythmias requiring medication or implantable cardioverter-defibrillator (ICD) therapy, uncontrolled supraventricular arrhythmias
      • clinically significant valvular disease
      • poorly controlled arterial hypertension (systolic blood pressure (BP) >180 mmHg, diastolic BP >100 mmHg)
    • Sensory/motor neuropathy > grade 2 as defined by National Cancer Institure - Common Toxicity Criteria (NCI-CTC)
    • Pregnancy, or intending to become pregnant during the study
    • Nursing (breastfeeding) or intending to be nursing during the study
    • Any of the following clinical conditions:

      • Chronic obstructive pulmonary disease, requiring chronic treatment
      • Clinically significant active infections
      • A history of a psychological illness of condition, preventing the subject to understand the requirements of the study
      • Unstable regulation of diabetes mellitus
    • A situation or condition that, in the opinion of the investigator, may interfere with optimal participation in the study
    • Is on staff, affiliated with, or a family member of the staff personnel directly involved with this study
    • Usage of any investigational product within 30 days prior to enrollment
    • Participation in any other interventional clinical study involving drug, device or biological. This would not prohibit the patient from participating in a quality of life (QOL), questionnaire, blood collection, or observational study.
    • Allergy to or sensitivity to the study drug or its excipients
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
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 Not Provided
Removed Location Countries Australia,   Belgium,   Canada,   Germany,   Italy,   Netherlands,   Spain,   Switzerland
 
Administrative Information
NCT Number  ICMJE NCT00550771
Other Study ID Numbers  ICMJE P05048
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php

Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Merck Sharp & Dohme Corp.
Verification Date May 2017

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