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

NCT00550771 | Completed Phase 2 Results

• 1 other identifier: P05048
• Study Type: interventional
• Target: 181
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (3)

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

  During the 8 courses of chemotherapy

• Number of Participants Who Experienced Cardiac Events (Level 1 or 2) or Inability to Administer Trastuzumab During 1 Year of Trastuzumab Therapy

  During 1 year of trastuzumab therapy

• Number of Participants Who Survived Without Relapse

  Approximately 2 years

Study Arms (2)

Doxorubicin Based Regimen

ACTIVE COMPARATOR

Drug: doxorubicin, cyclophosphamide, paclitaxel, trastuzumab

Pegylated Liposomal Doxorubicin (PLD) Based Regimen

EXPERIMENTAL

Drug: PLD, cyclophosphamide, trastuzumab, paclitaxel

Interventions

doxorubicin, cyclophosphamide, paclitaxel, trastuzumab 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)

Doxorubicin Based Regimen

PLD, cyclophosphamide, trastuzumab, paclitaxel 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)

Also known as: pegylated liposomal doxorubicin (SCH 200746)

Pegylated Liposomal Doxorubicin (PLD) Based Regimen

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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\[s\])

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 22056854 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin; Cyclophosphamide; Paclitaxel; Trastuzumab; 1-dodecylpyridoxal; liposomal doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Any follow-up data from this study should be considered with caution as the planned 2-year follow-up was curtailed because of administrative reasons.

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2007
• First Posted: October 30, 2007
• Study Start: July 16, 2007
• Primary Completion: August 23, 2010
• Study Completion: August 23, 2010
• Last Updated: June 7, 2017
• Results First Posted: October 3, 2011

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share