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Breast NeoplasmPhase 2NCT00550771

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

A Phase 2 study testing doxorubicin, cyclophosphamide, paclitaxel, trastuzumab and PLD, cyclophosphamide, trastuzumab, paclitaxel in people with Breast Neoplasm, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Neoplasm
What is being tested?
doxorubicin, cyclophosphamide, paclitaxel, trastuzumab and PLD, cyclophosphamide, trastuzumab, paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
181 participants
Where
No sites listed yet
Study dates
16 Jul 2007to 23 Aug 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 23Show fewer
  • 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

Who cannot join

  • 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
Show all 24Show fewer
  • 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

About this study

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

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.

Conditions
Breast Neoplasm
Being tested
doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, PLD, cyclophosphamide, trastuzumab, paclitaxel
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • doxorubicin, cyclophosphamide, paclitaxel, trastuzumabDrug

    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)

  • PLD, cyclophosphamide, trastuzumab, paclitaxelDrug

    Also called pegylated liposomal doxorubicin (SCH 200746)

    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)

Study groups in NCT00550771
Study groupRoleWhat they receive
Doxorubicin Based RegimenActive comparatorNot described
Receives: Drug: doxorubicin, cyclophosphamide, paclitaxel, trastuzumab
Pegylated Liposomal Doxorubicin (PLD) Based RegimenExperimentalNot described
Receives: Drug: PLD, cyclophosphamide, trastuzumab, paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    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.

    Measured: 8 cycles of chemotherapy and subsequently one year of planned trastuzumab treatment

Secondary outcomes (3)

  1. Number of Participants Who Experienced Cardiac Events (Level 1 or 2) or Inability to Administer Trastuzumab During the 8 Cycles 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.

    Measured: During the 8 courses of chemotherapy

  2. Number of Participants Who Experienced Cardiac Events (Level 1 or 2) or Inability to Administer Trastuzumab 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.

    Measured: During 1 year of trastuzumab therapy

  3. Number of Participants Who Survived Without Relapse

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

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

    Measured: Approximately 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2007 (estimated)
  2. Study start16 Jul 2007
  3. Primary completion23 Aug 2010
  4. Study completion23 Aug 2010

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
181 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00550771
Sponsor's protocol ID
P05048
Status last verified
May 2017
First submitted
29 Oct 2007
Last updated
7 Jun 2017
Individual data sharing
Yes: 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

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.

    PubMed 22056854

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing doxorubicin, cyclophosphamide, paclitaxel, trastuzumab and PLD, cyclophosphamide, trastuzumab, paclitaxel in people with Breast Neoplasm, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Oct 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00550771, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2017.

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