Epirubicin in Treating Women Who Are Undergoing Surgery for Stage I, Stage II, or Stage III Breast Cancer

Prediction of Response or Resistance to Dose Intensified Pre-Operative Epirubicin Therapy of Operable Breast Cancer

RATIONALE: Drugs used in chemotherapy, such as epirubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving epirubicin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well epirubicin works in treating women who are undergoing surgery for stage I, stage II, or stage III breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Biological: pegfilgrastim; Drug: epirubicin hydrochloride; Procedure: conventional surgery

Detailed Description

OBJECTIVES:

Primary

• Determine the complete pathological and clinical response rate in women undergoing surgery for resectable stage I-III breast cancer treated with neoadjuvant dose-intensified epirubicin hydrochloride.

Secondary

• Determine the toxicity of this regimen in these patients.
• Determine the predictive value of HER2 gene amplification and topoisomerase II-alpha gene amplification or deletion for disease progression and pathological and clinical complete response in patients treated with this regimen.
• Correlate gene expression profiles with pathologic complete response, clinical complete response, less than complete response, and disease progression in patients treated with this regimen.

OUTLINE: Patients receive epirubicin hydrochloride IV on day 1 and pegfilgrastim subcutaneously on day 2. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks later, patients undergo partial mastectomy or simple mastectomy plus an axillary staging procedure.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195-9001
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast cancer

  • Stage I, II, or III disease (T1, T2, or T4; N0-2; M0)

    • Resectable disease

• Unidimensionally measurable disease

  • Primary tumor ≥ 2 cm
• No known distant metastases

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,500/mm^3
• Hemoglobin ≥ 8 g/dL
• Platelet count ≥ 100,000/mm^3
• No known untreated bleeding diathesis

Hepatic

• AST ≤ 2 times upper limits of normal
• Bilirubin ≤ 1.5 mg/dL

Renal

• Creatinine ≤ 1.5 mg/dL OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• LVEF ≥ 50% on echocardiogram, MUGA, or cardiac catheterization

Other

• Not pregnant or breastfeeding
• Fertile patients must use effective contraception
• Negative pregnancy test
• No concurrent illness that would preclude study treatment
• No known hypersensitivity to Escherichia coli-derived proteins, pegfilgrastim, filgrastim (G-CSF), or any other component of these products

PRIOR CONCURRENT THERAPY: Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Epirubicin	Biological: pegfilgrastim; 6 mg in a syringe; Other Names: Neulasta; Drug: epirubicin hydrochloride; 120 MG q 2 weeks for 4 cycles; Procedure: conventional surgery; to remove small piece of cancer; Other Names: Biopsy will involve a small surgical incision to remove a piece of the cancer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete pathological response rate by tumor analysis after surgery	No evidence of microscopic invasive tumor at the primary tumor site in the surgical specimen.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete clinical response rate by diagnostic mammogram at baseline and at 8 weeks	Bilateral (if both breasts are present) Mammograms (within 4 weeks of study entry)	4 weeks
Toxicity by physical exam and medical history every 14 days prior to surgery	A physical exam Physical examination with recording of tumor size, if palpable.	2-4 weeks
Predictive value of HER2 gene amplification and topoisomerase II-alpha gene amplification or deletions for pathologic complete response, clinical complete response or disease progression after surgery	Patients whose tumors are positive for estrogen receptor (>1% staining by immunohistochemistry) or progesterone receptor (institutional definition) should receive post-operative hormonal therapy for 5 years.	5 years
Gene expression after surgery	Patients whose tumors are positive for estrogen receptor (>1% staining by immunohistochemistry) or progesterone receptor (institutional definition) should receive post-operative hormonal therapy for 5 years.	5 years

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Study Chair: George T. Budd, MD, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

Study record dates

Study Major Dates

• Study Start: June 1, 2002
• Primary Completion (Actual): September 1, 2005
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: November 11, 2005
• First Submitted That Met QC Criteria: November 11, 2005
• First Posted (Estimate): November 15, 2005

Study Record Updates

• Last Update Posted (Actual): July 24, 2020
• Last Update Submitted That Met QC Criteria: July 22, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; stage IIIB breast cancer; stage II breast cancer; stage I breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Epirubicin
• Other Study ID Numbers: CASE3104