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A Safety and Efficacy Study of Doxil and Taxotere +/- Herceptin in Advanced Breast Cancer

Phase 2
18 Years
Not Enrolling
Metastatic Breast Cancer

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Trial Information

A Safety and Efficacy Study of Doxil and Taxotere +/- Herceptin in Advanced Breast Cancer


I. Assess the safety, toxicity, and feasibility of doxorubicin hydrochloride (HCL) liposome
and docetaxel with or without trastuzumab (Herceptin™) in patients with metastatic breast
cancer, particularly with respect to cardiotoxicity.

II. Assess the overall objective response rate, response duration, time to treatment
failure, and median survival of these patients with these treatment regimens.

III. Assess any association between trough plasma levels of cardiac troponin T and brain
natriuretic peptide and any cardiac event (congestive heart failure or left ventricular
ejection fraction decrease).

OUTLINE: Patients are assigned to one of two treatment arms according to HER2 overexpression

Arm I (HER2 nonoverexpressed): Patients receive doxorubicin hydrochloride liposome IV over
30 minutes followed by docetaxel IV over 1 hour. Treatment is repeated every 3 weeks for 8
courses in the absence of disease progression or unacceptable toxicity.

Patients may receive maintenance therapy of docetaxel IV over 1 hour either weekly or every
3 weeks. Maintenance continues in the absence of disease progression or unacceptable

Arm II (HER2 overexpressed): Patients receive trastuzumab IV over 90 minutes on day 1, with
subsequent doses over 30 minutes. Patients receive doxorubicin HCl liposome IV over 30
minutes followed by docetaxel IV over 1 hour on day 2 of course 1, followed by subsequent
doses on day 1 of each course. Antibody therapy continues weekly and chemotherapy every 3
weeks for 8 courses.

Patients may receive maintenance therapy of trastuzumab IV over 30 minutes weekly followed
by docetaxel IV over 1 hour weekly or every 3 weeks. Maintenance continues in the absence of
disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
annually thereafter.

Inclusion Criteria:

- Histologically confirmed metastatic adenocarcinoma of the breast

- HER2 nonoverexpressed (0-1+) OR overexpressed (2-3+)

- Measurable or evaluable disease

- Prior brain metastases responsive to treatment of radiotherapy and/or surgery allowed
(cannot be only site of metastases)

- Age 18 and over

- Female

- Fertile women must use effective contraception

- Eastern Cooperative Oncology Group performance status of 0,1,or 2

- The following lab values obtained at least 4 weeks prior to registration: granulocyte
count at least 1,500/mm^3, platelet count at least 100,000/mm^3, SGOT no greater than
2.5 times upper limit of normal, bilirubin normal, and creatinine no greater than 1.5

- Left ventricular ejection fraction at least lower limit of normal (LLN)

- Prior adjuvant chemotherapy allowed if completed 6 months before metastasis

- Prior endocrine therapy in either a metastatic or adjuvant setting, but patients must
have been off such therapy for at least 2 weeks prior to registration

- Prior radiotherapy allowed only to conserved breast, postmastectomy chest wall with
or without internal mammary lymph node chain (IMN), or field containing less than 25%
bone marrow

- At least 2 weeks since prior radiotherapy

- At least 2 weeks since surgery (including mastectomy) and recovered

Exclusion Criteria:

- Prior deep venous thrombosis or thromboembolic condition

- Prior myocardial infarction or congestive heart failure

- Arrhythmia requiring medication

- Hypertension or systolic or diastolic dysfunction

- Ventricular hypertrophy or conduction abnormality

- Prior pulmonary thromboembolism

- Other malignancy within the past 5 years except curatively treated carcinoma in
situ of the cervix or basal cell or squamous cell carcinoma of the skin

- Pregnant or nursing

- Prior trastuzumab (Herceptin™)

- Prior chemotherapy for advanced or local/regional recurrent disease

- Prior anthracyclines or anthracenediones

- Prior photon IMN treatment

- Concurrent radiotherapy

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Grades of Cardiotoxicity Events in the Subset of Patients Reporting a Cardiotoxicity Event

Outcome Description:

This table summarizes the cardiotoxicity events of different grades. Grade 1 is a decline of left ventricular ejection fraction(LVEF) >=10% but <20% of baseline value. Grade 2 is LVEF below LLN (50%) or decline of LVEF >=20% of baseline value. Grade 3 is congestive heart failure responsive to treatment. Please note that only a subset of patients reported cardiotoxic events so the totals will not add up to the total number of participants.

Outcome Time Frame:

Baseline, after cycle 4 (~84 days), after cycle 8 (~168 days), and 30 or more days after last cycle of induction therapy

Safety Issue:


Principal Investigator

Antonio C. Wolff, MD

Investigator Role:

Study Chair

Investigator Affiliation:

The Johns Hopkins Oncology Center Cancer Research Building


United States: Federal Government

Study ID:




Start Date:

October 2000

Completion Date:

May 2009

Related Keywords:

  • Metastatic Breast Cancer
  • Stage IV breast cancer
  • Recurrent breast cancer
  • HER2 Overexpression
  • Trastuzumab
  • Nonpegylated liposomal doxorubicine
  • Metastatic breast cancer
  • Cardiac toxicity
  • Breast Neoplasms



CCOP - Carle Cancer Center Urbana, Illinois  61801
CCOP - Iowa Oncology Research Association Des Moines, Iowa  50309-1016
CCOP - Kalamazoo Kalamazoo, Michigan  49007-3731
CCOP - Metro-Minnesota Saint Louis Park, Minnesota  55416
West Michigan Cancer Center Kalamazoo, Michigan  49007-3731
CCOP - Duluth Duluth, Minnesota  55805
Penn State Cancer Institute at Milton S. Hershey Medical Center Hershey, Pennsylvania  17033-0850
CCOP - Merit Care Hospital Fargo, North Dakota  58122
CCOP - Sioux Community Cancer Consortium Sioux Falls, South Dakota  57105-1080
CCOP - Columbus Columbus, Ohio  43206
CCOP - MainLine Health Wynnewood, Pennsylvania  19096
CCOP - Northern Indiana CR Consortium South Bend, Indiana  46601
MetroHealth's Cancer Care Center at MetroHealth Medical Center Cleveland, Ohio  44106
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
CCOP - St. Vincent Hospital Cancer Center, Green Bay Green Bay, Wisconsin  54301
Albert Einstein Clinical Cancer Center Bronx, New York  10461
Tufts - New England Medical Center Boston, Massachusetts  02111
Winship Cancer Institute of Emory University Atlanta, Georgia  30322
CCOP - Marshfield Clinic Research Foundation Marshfield, Wisconsin  54449
Cancer Institute of New Jersey at Robert Wood Johnson University Hospital New Brunswick, New Jersey  08903
MBCCOP-Our Lady of Mercy Cancer Center Bronx, New York  10466
Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago, Illinois  60611
Lankenau Cancer Center at Lankenau Hospital Wynnewood, Pennsylvania  19096