Doxorubicin or Epirubicin and Cyclophosphamide in Treating Older Women With Invasive Breast Cancer

Adjuvant Cytotoxic Chemotherapy In Older Women

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, epirubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether giving doxorubicin or epirubicin together with cyclophosphamide is more effective than observation in treating older women with invasive breast cancer.

PURPOSE: This randomized phase III trial is studying doxorubicin or epirubicin and cyclophosphamide to see how well they work compared with observation in treating older women with invasive breast cancer.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: cyclophosphamide; Other: pharmacological study; Genetic: proteomic profiling; Procedure: adjuvant therapy; Drug: doxorubicin hydrochloride; Other: diagnostic laboratory biomarker analysis; Drug: epirubicin hydrochloride; Biological: pegfilgrastim; Other: matrix-assisted laser desorption/ionization time of flight mass spectrometry; Other: surface-enhanced laser desorption/ionization-time of flight mass spectrometry

Detailed Description

OBJECTIVES:

• To provide evidence for extending the current standard care in older women with invasive breast carcinoma treated with adjuvant chemotherapy comprising doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide.
• Compare the relapse-free survival interval of these patients treated with adjuvant chemotherapy vs no adjuvant chemotherapy.
• Compare the toxicity of accelerated adjuvant chemotherapy with pegfilgrastim support vs non-accelerated adjuvant chemotherapy.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center and indication for endocrine therapy (yes vs no). Patients are randomized to 1 of 2 arms.

• Arm I (observation): Patients do not receive adjuvant chemotherapy.

• Arm II (adjuvant chemotherapy): Patients are randomized to 1 of 2 chemotherapy regimens.

  • Accelerated adjuvant chemotherapy: Patients receive doxorubicin hydrochloride and cyclophosphamide (AC) OR epirubicin hydrochloride and cyclophosphamide (EC) on day 1 and pegfilgrastim on day 2. Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
  • Non-accelerated adjuvant chemotherapy: Patients receive AC or EC on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor tissue and blood sample collection for biological, pharmacological, and proteomic studies. Samples are initially used to establish a resource of materials available for different research groups. Samples are also analyzed using SELDI or MALDI-ToF technology to identify biological profiles that correlate with prognosis or predict response to treatment.

Quality of life is assessed at baseline, 6 weeks, 1 month, 6 months, 9 months, 12 months, 18 months, and 24 months.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually thereafter.

• Study Type: Interventional
• Enrollment (Anticipated): 1000
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • London, England, United Kingdom, W6 8RF
      • Recruiting
      • Charing Cross Hospital
      • Contact: Robert C.F. Leonard, MD, BS, MB; Phone Number: 44-208-846-7237
    • Westcliff-On-Sea, England, United Kingdom, SS0 0RY
      • Recruiting
      • Southend University Hospital NHS Foundation Trust
      • Contact: Anne Robinson, MD; Phone Number: 44-1702-221-226

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast carcinoma

• Primary operable breast cancer that was surgically treated by wide local excision or mastectomy with clear margins (> 1 mm apart from deep margin if full thickness resection)

  • No more than 8 weeks since prior definitive surgery

• Early-stage disease with no evidence of metastases clinically or on routine staging investigations

  • No T4 and/or N3 disease

• Prior axillary staging required, including 1 of the following:

  • Sentinel node biopsy

  • Axillary sampling or clearance

    • All node-positive patients must have had axillary clearance or radiotherapy to the axilla
• Must be at high risk of relapse within 5 years (risk factors evaluated at clinician's discretion)
• No other invasive breast cancer, systemically treated ductal carcinoma in situ (DCIS), or solid tumor within the past 5 years
• No prior hematologic malignancy or melanoma

• Hormone receptor status:

  • Estrogen receptor (ER)- or progesterone receptor (PR)-negative OR ER/PR-weakly positive (e.g., Allred/Quick score ≤ 5 OR H score ≤ 100)

PATIENT CHARACTERISTICS:

• Female
• Postmenopausal
• Performance status 0-1
• Hemoglobin > 9 g/dL
• WBC > 3,000/mm³
• Platelet count > 100,000/mm³
• Bilirubin normal (unless known Gilbert's disease is present)
• Albumin normal
• AST and ALT ≤ 1.5 x upper limit of normal (ULN)
• Creatinine ≤ 1.5 x ULN
• Creatinine clearance > 50 mL/min
• No active or uncontrolled infection
• Must be available for routine long-term hospital follow-up
• Must have normal cardiac function and no significant cardiac disease by ECHO or MUGA

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 4 weeks since prior preoperative endocrine therapy
• No prior systemic therapy for this breast cancer or mantle radiotherapy
• No prior breast-conserving surgery in which there is a contraindication for, or decline of postoperative radiotherapy
• No concurrent hormone replacement therapy (HRT)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Relapse-free interval
Physical, functional, and breast cancer concerns as measured by the Trial Outcome Index (TOI)
Total FACT-AN score
Total FACT-F score

Secondary Outcome Measures

Outcome Measure
Overall survival
Quality of life
Disease-free survival
Cause-specific survival
Distant disease-free survival
Safety and tolerability (overall and for each treatment schedule)
Treatment compliance (overall and for each treatment schedule)
Total FACT-B score
Individual subscales on activities of daily living

Collaborators and Investigators

• Sponsor: Charing Cross Hospital
• Investigators: Principal Investigator: Robert C.F. Leonard, MD, BS, MB, Charing Cross Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2007

Study Registration Dates

• First Submitted: August 14, 2007
• First Submitted That Met QC Criteria: August 14, 2007
• First Posted (Estimate): August 15, 2007

Study Record Updates

• Last Update Posted (Estimate): August 7, 2013
• Last Update Submitted That Met QC Criteria: August 6, 2013
• Last Verified: September 1, 2007

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; stage II breast cancer; stage IA breast cancer; stage IB breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclophosphamide; Epirubicin; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: UKM-CCH-ACTION; CDR0000561076 (Registry Identifier: PDQ (Physician Data Query)); ICR-CTSU/2006/10004-ACTION; EU-20751; EUDRACT-2005-005721; ISRCTN41708421; BIG-205