Clinical trial NCT00516425: Doxorubicin or Epirubicin and Cyclophosphamide in Treating Older Women With Invasive Breast Cancer
Official title: Adjuvant Cytotoxic Chemotherapy In Older Women
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Cancer
Keywords: stage IA breast cancer
stage IB breast cancer
stage II breast cancer
stage IIIA breast cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-08-15
Enrollment: 1000
Sex: FEMALE
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Relapse-free interval
measure: Physical, functional, and breast cancer concerns as measured by the Trial Outcome Index (TOI)
measure: Total FACT-AN score
measure: Total FACT-F score
Secondary outcomes:
measure: Disease-free survival
measure: Overall survival
measure: Cause-specific survival
measure: Distant disease-free survival
measure: Safety and tolerability (overall and for each treatment schedule)
measure: Treatment compliance (overall and for each treatment schedule)
measure: Quality of life
measure: Total FACT-B score
measure: Individual subscales on activities of daily living
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Charing Cross Hospital
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
state: England
Study officials:
affiliation: Charing Cross Hospital
name: Robert C.F. Leonard, MD, BS, MB
role: PRINCIPAL_INVESTIGATOR
References: