Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy With or Without Trastuzumab in Treating Women With Metastatic Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	ECOG-3198 E3198, NCT00004888

Objectives

1. Assess the safety, toxicity, and feasibility of doxorubicin HCl liposome and docetaxel with or without trastuzumab (Herceptin™) in patients with metastatic breast cancer, particularly with respect to cardiotoxicity.
2. Assess the overall objective response rate, response duration, time to treatment failure, and median survival of these patients with these treatment regimens.
3. Assess any association between trough plasma levels of cardiac troponin T and brain natriuretic peptide and any cardiac event (congestive heart failure or LVEF decrease).

Entry Criteria

Disease Characteristics:

• Histologically confirmed metastatic adenocarcinoma of the breast



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



• Measurable or evaluable disease
  • Pleural or peritoneal effusions allowed if local intracavitary treatment not started at onset of therapy
  • Blastic or mixed blastic/lytic osseous metastases allowed if accompanied by pain or decreased performance status, and do not require radiotherapy within two courses of study therapy
  • Osteolytic disease allowed if proven by x-ray
  • No abnormal bone scan without confirmatory x-rays as only evidence of metastatic disease



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



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy:

• No prior trastuzumab (Herceptin™)

Chemotherapy:

• No prior chemotherapy for advanced or local/regional recurrent disease
• Prior adjuvant chemotherapy allowed if completed 6 months before metastasis
• No prior anthracyclines or anthracenediones

Endocrine therapy:

• At least 2 weeks since prior hormonal therapy

Radiotherapy:

• 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
• No prior photon IMN treatment
• At least 2 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

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

Patient Characteristics:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• SGOT no greater than 2.5 times upper limit of normal
• Bilirubin normal

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No prior deep venous thrombosis or thromboembolic condition
• LVEF at least lower limit of normal
• No prior myocardial infarction or congestive heart failure
• No arrhythmia requiring medication
• No hypertension or systolic or diastolic dysfunction
• No ventricular hypertrophy or conduction abnormality

Pulmonary:

• No prior pulmonary thromboembolism

Other:

• No 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
• Not pregnant or nursing
• Fertile women must use effective contraception

Expected Enrollment

A total of 92 patients (46 per arm) will be accrued for this study within 13 months.

Outline

Patients are assigned to one of two treatment arms according to HER2 overexpression status.

• Arm I (HER2 nonoverexpressed): Patients receive doxorubicin HCl 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 toxicity.




• 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.

Wolff AC, Wang M, Sparano JA, et al.: Cardiac safety and clinical activity of pegylated liposomal doxorubicin (D) and docetaxel (T) with and without trastuzumab (H) as 1st line chemotherapy in HER2-positive and HER2-negative metastatic breast cancer (MBC): Eastern Cooperative Oncology Group (ECOG) trial E3198. [Abstract] Breast Cancer Res Treat 88 (Suppl 1): A-3040, 2004.

Wolff AC, Bonetti M, Sparano JA, et al.: Cardiac safety of trastuzumab (H) in combination with pegylated liposomal doxorubicin (D) and docetaxel (T) in HER2-positive metastatic breast cancer (MBC): preliminary results of the Eastern Cooperative Oncology Group trial E3198. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-70, 2003.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Antonio Wolff, MD, Protocol chair		Ph: 410-614-4192 Email: awolff@jhmi.edu

Registry Information
Official Title		A Safety and Efficacy Study of Doxil and Taxotere +/- Herceptin in Advanced Breast Cancer
Trial Start Date		2000-10-19
Trial Completion Date		2009-05-18
Registered in ClinicalTrials.gov		NCT00004888
Date Submitted to PDQ		2000-01-12
Information Last Verified		2004-04-27
NCI Grant/Contract Number		U10-CA21115

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