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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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00550771
First received: October 29, 2007
Last updated: August 12, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Breast Neoplasm
Drug: doxorubicin, cyclophosphamide, paclitaxel, trastuzumab
Drug: PLD, cyclophosphamide, trastuzumab, paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: No ]

    Relapse-free survival would have been determined by Kaplan-Meier method.

    This was not calculated, since the 2 year follow-up was curtailed.



Enrollment: 181
Study Start Date: July 2007
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Doxorubicin Based Regimen 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)
Experimental: Pegylated Liposomal Doxorubicin (PLD) Based Regimen 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)

  Eligibility

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

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
  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.

No Contacts or Locations Provided
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00550771     History of Changes
Other Study ID Numbers: P05048
Study First Received: October 29, 2007
Results First Received: August 26, 2011
Last Updated: August 12, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Trastuzumab
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Paclitaxel
Alkylating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators

ClinicalTrials.gov processed this record on November 27, 2014