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

NCT ID: NCT00550771

Last Updated: 2017-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 181 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-16
• Study Completion Date: 2010-08-23

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.

Conditions

Breast Neoplasm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Doxorubicin Based Regimen

Group Type: ACTIVE_COMPARATOR

doxorubicin, cyclophosphamide, paclitaxel, trastuzumab

Intervention Type: DRUG

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)

Pegylated Liposomal Doxorubicin (PLD) Based Regimen

Group Type: EXPERIMENTAL

PLD, cyclophosphamide, trastuzumab, paclitaxel

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

pegylated liposomal doxorubicin (SCH 200746)

Eligibility 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

References

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.

Reference Type: DERIVED

PMID: 22056854 (View on PubMed)

Other Identifiers

P05048

Identifier Type: -

Identifier Source: org_study_id