Clinical trial NCT00309920: Combination Chemotherapy With or Without Darbepoetin Alfa in Treating Women With Stage III Breast Cancer
Official title: Adjuvant Therapy of Breast Cancer: Impact of Erythropoiesis Stimulating Factors on Event Free Survival High Risk Breast Cancer Treatment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Cancer
Keywords: stage IIIA breast cancer
stage IIIC breast cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-04-03
Enrollment: 1234
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Colony-stimulating factors, such as darbepoetin alfa, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving combination chemotherapy together with darbepoetin alfa after surgery may kill any tumor cells that remain after surgery. It is not yet known whether combination chemotherapy and darbepoetin alfa are more effective than combination chemotherapy alone in treating stage III breast cancer.

PURPOSE: This randomized clinical trial is studying how well giving combination chemotherapy together with darbepoetin alfa works compared to combination chemotherapy alone in treating women with stage III breast cancer.

Detailed description: OBJECTIVES:

Primary

* Compare the disease-free survival rate in women with stage III breast cancer treated with adjuvant chemotherapy with vs without darbepoetin alfa.

Secondary

* Compare local recurrence and overall survival in patients receiving these regimens.
* Compare toxicity of these regimens in these patients.
* Compare quality of life and fatigue frequency in patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according the chemotherapy regimen (CEF vs TAC). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive 1 of the following regimens:

  * Regimen CEF: Patients receive cyclophosphamide IV, epirubicin hydrochloride IV, and fluorouracil IV on day 1.
  * Regimen TAC: Patients receive docetaxel IV, doxorubicin hydrochloride IV, and cyclophosphamide IV on day 1.

Treatment repeats every 3 weeks for 6 courses in the absence of disease progression and unacceptable toxicity.

* Arm II: Patients receive 1 of the following regimens:

  * Regimen CEF: Patients receive regimen CEF as in arm I. Patients receive darbepoetin alfa if hemoglobin falls to ≤ 13.0 g/dL. Darbepoetin alfa is discontinued when hemoglobin rises to \> 14.0 g/dL.
  * Regimen TAC: Patients receive TAC as in arm I and darbepoetin alfa as in arm II, regimen CEF.

Quality of life is assessed at baseline, before each chemotherapy course, at the completion of study therapy, and at 6 and 12 months.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 1,234 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed breast cancer

  * Stage III disease (pT1, N2-3, M0)
  * No metastatic disease by thoracic x-ray, full-body bone scan, and liver sonography
* No inflammatory disease or Paget's disease
* Disease completely resected (R0) and ≥ 10 axillary lymph nodes removed

  * Underwent surgery approximately 42 days ago
  * At least 9 positive lymph nodes
  * No prior sequential mastectomy
* Hormone receptor status not specified

PATIENT CHARACTERISTICS:

* Female
* Menopausal status not specified
* ECOG performance status 0-1
* WBC ≥ 3,500/mm\^3
* Creatinine ≤ 1.4 mg/dL
* Platelet count ≥ 100,000/mm\^3
* Bilirubin ≤ 2.0 mg/dL
* No pre-existing symptomatic peripheral neuropathy
* Not pregnant or nursing
* No hypersensitivity to darbepoetin alfa, epoetin alfa, or any of their components
* No other malignancy except curatively treated basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No participation in another clinical study
* No prior therapies that would preclude study participation

Primary outcomes:
measure: Disease-free survival at 6 months to 5 years after treatment
Secondary outcomes:
measure: Overall survival at 6 months to 5 years after treatment
measure: Toxicity by NCI toxicity criteria at every course and periodically thereafter
measure: Anemia and cognitive function by Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog) at every course
measure: Local relapses at 6 months to 5 years after treatment
Other outcomes:
Locations:
city: Aurich
country: Germany
facility: Kreiskrankenhaus Aurich
city: Bergheim
country: Germany
facility: Maria-Hilf-Krankenhaus
city: Bergisch
country: Germany
facility: Evangelisches Krankenhaus - Bergisch Gladbach
city: Bochum-Langendreer
country: Germany
facility: Knappschaft Krankenhaus
city: Bonn-Duisdorf
country: Germany
facility: Praxis fuer Haematologie - Onkologie
city: Bonn
country: Germany
facility: Johanniter-Krankenhaus Bonn
city: Bonn
country: Germany
facility: Onkologische Gemeinschaftspraxis
city: Castrop-Rauxel
country: Germany
facility: St. Rochus Hospital
city: Cologne
country: Germany
facility: Praxis Fuer Haematologie Internistische Onkologie
city: Cologne
country: Germany
facility: Medizinische Universitaetsklinik I at the University of Cologne
city: Cologne
country: Germany
facility: St. Elisabeth-Krankenhaus - Koeln
city: Deggendorf
country: Germany
facility: Klinikum Deggendorf
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf
city: Duisburg
country: Germany
facility: Onkologische Schwerpunktpraxis
city: Essen
country: Germany
facility: Alfried Krupp Krankenhaus
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Fuerth
country: Germany
facility: II Medizinische Klinik - Klinikum Fuerth
city: Gelsenkirchen
country: Germany
facility: Evangelische Kliniken Gelsenkirchen GmbH
city: Goch
country: Germany
facility: Wilhelm-Anton-Hospital gGmbH, Goch
city: Greven
country: Germany
facility: Maria-Josef-Hospital Greven GmbH
city: Hagen
country: Germany
facility: Allgemeines Krankenhaus Hagen
city: Hagen
country: Germany
facility: Evangelisches Krankenhaus Hagen-Haspe GmbH
city: Hannover
country: Germany
facility: Henriettenstiftung Krankenhaus
city: Hildesheim
country: Germany
facility: Praxisgemeinschaft fuer Gynaekologische Onkologie
city: Homburg
country: Germany
facility: Universitaetsklinikum des Saarlandes
city: Kaufbeuren
country: Germany
facility: Klinikum Kaufbeuren Ostallgaeu
city: Koblenz
country: Germany
facility: Katholisches Klinikum Koblenz Marienhof
city: Kronach
country: Germany
facility: Frankenwald Klinik
city: Kronach
country: Germany
facility: Internistische Onkologische Praxis - Kronach
city: Luenen
country: Germany
facility: St. Marien Hospital - Luenen
city: Mainz
country: Germany
facility: St. Vincenz und Elisabeth Hospital
city: Memmingen
country: Germany
facility: Klinikum Memmingen
city: Minden
country: Germany
facility: Klinikum Minden
city: Moers
country: Germany
facility: Krankenhaus Bethanien
city: Neuwied
country: Germany
facility: Marienhaus Klinikum St. Elisabeth Neuwied
city: Oberhausen
country: Germany
facility: Evangelisches Krankenhaus Oberhausen
city: Offenbach
country: Germany
facility: Internistische Gemeinschaftspraxis - Offenbach
city: Rheine
country: Germany
facility: Praxis fuer Haematologie und Onkoligie
city: Rostock
country: Germany
facility: Klinikum Suedstadt Rostock
city: Schwerte
country: Germany
facility: Marienkrankenhaus Schwerte gem. GmbH
city: Solingen
country: Germany
facility: Staedtisches Klinikum Solingen
city: Troisdorf
country: Germany
facility: Praxis Fuer Internistische Haematologie / Onkologie
city: Unna
country: Germany
facility: Katherinen-Hospital gGmbH
city: Wesel
country: Germany
facility: Marien-Hospital Wesel gGmbH
city: Witten
country: Germany
facility: Marien-Hospital Witten
city: Wuppertal
country: Germany
facility: Bethesda Krankenhaus Wuppertal gGmbH
city: Wuppertal
country: Germany
facility: Haematologie / Onkologische Schwerpunktpraxis
Study officials:
affiliation: Heinrich-Heine University, Duesseldorf
name: Ulrike Nitz, PhD
role: STUDY_CHAIR
References: