Doxorubicin and Cyclophosphamide in Treating Older Women With Stage I, Stage II, or Stage III Breast Cancer That Has Been Removed By Surgery

Multicenter Pilot Clinical Study of Adjuvant Chemotherapy for Subjects Over 70 Years: Impact on the Independence and Quality of Life of the Administration of Anthracycline-Based Chemotherapy in Adjuvant Setting for Patients Presenting With Immediately Operable Breast Cancer, Hormone Receptor Negative (RH-), and Lymph Node Positive (pN+) or pN0 But of Scarff-Bloom-Richardson* Grade III and ≥ 2cm [GERICO]

RATIONALE: Drugs used in chemotherapy, such as doxorubicin 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.

PURPOSE: This phase II trial is studying how well giving doxorubicin together with cyclophosphamide works in treating older women with stage I , stage II, or stage III breast cancer that has been removed by surgery.

Study Overview

• Status: Completed
• Conditions: Depression; Breast Cancer; Malnutrition; Cognitive/Functional Effects; Psychosocial Effects of Cancer and Its Treatment
• Intervention / Treatment: Drug: cyclophosphamide; Procedure: psychosocial assessment and care; Procedure: adjuvant therapy; Drug: doxorubicin hydrochloride; Procedure: quality-of-life assessment; Procedure: cognitive assessment; Procedure: management of therapy complications; Drug: AC regimen

Detailed Description

OBJECTIVES:

Primary

• Determine the independence of older women with resected stage I, II, or III breast cancer treated with adjuvant doxorubicin hydrochloride and cyclophosphamide.

Secondary

• Determine the impact of this regimen on other aspects of the patient's life, utilizing the Comprehensive Geriatric Assessment, the Mini-Nutritional Assessment, the Folstein Mini-Mental State Exam, the Geriatric Depression Scale, and the Cumulative Illness Rating Scale-Geriatrics.
• Determine the quality of life of patients treated with this regimen.
• Determine the acceptability of this regimen in these patients.
• Determine the toxicity of this regimen, in terms of cardiac issues and anemia, in these patients.
• Determine recurrence-free survival, event-free survival, and overall survival of patients treated with this regimen.

OUTLINE: This is a pilot, nonrandomized, multicenter study.

Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients complete questionnaires at baseline and after completion of chemotherapy. Questionnaires include the Comprehensive Geriatric Assessment, the Mini-Nutritional Assessment (malnutrition), the Folstein Mini-Mental State Exam (cognitive function), the Geriatric Depression Scale (depression), the Cumulative Illness Rating Scale - Geriatrics (comorbidities), and the EORTC Quality of Life Questionnaire Core 30 (quality of life).

After completion of study therapy, patients are followed every 3 months for 4 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Angers, France, 49036
    • Centre Paul Papin
  • Avignon, France, 84082
    • Institut Sainte Catherine
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Clermont-Ferrand, France, 63011
    • Centre Jean Perrin
  • Levallois, France, 92309
    • Hopital Perpetuel Secours
  • Lyon, France, 69373
    • Centre léon Bérard
  • Marseille, France, 13273
    • Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
  • Nantes-Saint Herblain, France, 44805
    • Centre Regional Rene Gauducheau
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou
  • Paris, France, 75248
    • Institut Curie Hopital
  • Reims, France, 51056
    • Institut Jean Godinot
  • Rennes, France, 35042
    • Centre Eugène Marquis
  • Rouen, France, 76038
    • Centre Henri Becquerel
  • Saint Cloud, France, 92211
    • Centre René Huguenin
  • Senlis, France, 60309
    • C.H. Senlis
  • Toulouse, France, 31052
    • Institut Claudius Regaud
  • Vandoeuvre-les-Nancy, France, 54511
    • Centre Alexis Vautrin

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 adenocarcinoma of the breast

  • Stage I, II or III disease

    • pN+ or pN0 with grade III disease (tumor size ≥ 2 cm)
    • No metastatic disease

• Must have undergone prior conservative or radical surgery that included axillary lymph node or sentinel node dissection

  • No residual tumor
  • Negative margins

• Hormone receptor status:

  • Estrogen receptor and progesterone receptor negative

PATIENT CHARACTERISTICS:

• Female
• Postmenopausal
• Absolute neutrophil count > 1,500/mm³
• Platelet count > 100,000/mm³
• Hemoglobin > 10 g/dL
• Alkaline phosphatase < 2.5 times upper limit of normal (ULN)
• Bilirubin < 1.25 times ULN
• AST and ALT < 2.5 times ULN
• Creatinine clearance ≥ 40 mL/min
• No contraindication to receiving anthracyclines or alkalizing agents
• FEV normal

• Activities of Daily Living (ADL) score ≥ 5

  • No decrease of ≥ 1 point within the past 3 months

• None of the following at baseline:

  • Cognitive deficiency (Folstein Mini-Mental State < 25)
  • Severe depression (Geriatric Depression Scale ≥ 20)
  • Severe malnutrition (Mini-Nutritional Assessment ≤ 17)

• No other serious comorbid condition (Cumulative Illness Rating Scale - Geriatrics grade 3-4), including any of the following:

  • Cardiac insufficiency
  • Unstable angina
  • Myocardiopathy
  • Myocardial infarction within the past year
  • Uncontrolled hypertension
  • Uncontrolled high-risk arrhythmia
  • Severe medullary insufficiency
  • Neurological or psychological condition that would preclude study consent
  • Uncontrolled or active infection
  • Severe urinary tract infection
  • Preexisting hematuria
  • Active ulcer
  • Uncontrolled diabetes
• No other cancer within the past 5 years except for basal cell skin cancer or carcinoma in situ of the cervix
• No familial, geographical, social, or psychological condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 60 days since prior therapeutic surgery
• At least 4 weeks since prior investigational drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Myocet, Endoxan	Drug: cyclophosphamide; Procedure: psychosocial assessment and care; Procedure: adjuvant therapy; Drug: doxorubicin hydrochloride; Procedure: quality-of-life assessment; Procedure: cognitive assessment; Procedure: management of therapy complications; Drug: AC regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients maintaining their independence as assessed by Activities of Daily Living (ADL) score on 6 items after the fourth course of chemotherapy	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Impact of adjuvant chemotherapy on ADL score, quality of life, treatment acceptability, toxicity, and survival (recurrence-free, progression-free, and overall survival)	3 years

Collaborators and Investigators

• Sponsor: UNICANCER
• Investigators: Study Chair: E. G. C. Brain, MD, PhD, Institut Curie

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: January 16, 2007
• First Submitted That Met QC Criteria: January 16, 2007
• First Posted (Estimate): January 18, 2007

Study Record Updates

• Last Update Posted (Estimate): September 4, 2013
• Last Update Submitted That Met QC Criteria: September 2, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; stage IIIB breast cancer; depression; stage II breast cancer; stage IIIC breast cancer; stage IA breast cancer; stage IB breast cancer; estrogen receptor-negative breast cancer; malnutrition; progesterone receptor-negative breast cancer; cognitive/functional effects; psychosocial effects of cancer and its treatment
• Additional Relevant MeSH Terms: Behavioral Symptoms; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Nutrition Disorders; Depression; Breast Neoplasms; Malnutrition; 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; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: CDR0000523419; FRE-FNCLCC-GERICO-06-0502; EU-20667; EUDRACT-2005-000069-20