Epirubicin, Docetaxel, and Pegfilgrastim in Treating Women With Locally Advanced or Inflammatory Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00066443
First received: August 6, 2003
Last updated: January 16, 2014
Last verified: January 2014
  Purpose

RATIONALE: Drugs used in chemotherapy such as epirubicin and docetaxel use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as pegfilgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: Phase I/II trial to study the effectiveness of combining epirubicin and docetaxel with pegfilgrastim in treating women who have locally advanced or inflammatory breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: pegfilgrastim
Drug: docetaxel
Drug: epirubicin hydrochloride
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study Of Increasing Doses Of Epirubicin And Docetaxel Plus Pegfilgrastim For Locally Advanced Or Inflammatory Breast Cancer

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Toxic effects [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]
    Findings were presented at ASCO 2010

  • Response (phase II) [ Time Frame: 12 years ] [ Designated as safety issue: No ]
    Response was presented at ASCO 2010. Duration of response will be analyzed in 2015


Enrollment: 93
Study Start Date: February 2003
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pegfilgrastim, docetaxel and epirubicin Biological: pegfilgrastim
Dose escalation schedule A&B = 6mg fixed dose once per cycle on day 2
Drug: docetaxel
Dose Escalation schedule A = 75-85 mg/m2 Dose Escalation schedule B = 50-75 mg/m2
Drug: epirubicin hydrochloride
Dose escalation schedule A = 75-120 mg/m2 IV Dose escalation schedule B = 50-90 mg/m2 IV

Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose and recommended phase II dose of docetaxel and epirubicin when given with pegfilgrastim in women with locally advanced or inflammatory breast cancer. (Phase I, group 1 closed to accrual as of 9/13/04 and Phase II, group 1 closed to accrual as of 5/10/06)
  • Determine the toxicity of this regimen in these patients.
  • Determine the clinical and pathological response rate and duration of response in patients treated with this regimen.
  • Determine drug sensitivity and resistance in patients treated with this regimen.
  • Determine prognostic and predictive markers in patients treated with this regimen.

OUTLINE: This is a nonrandomized, multicenter, dose-escalation study of docetaxel and epirubicin.

  • Phase I:

Group 1 (21-day regimen) (closed to accrual as of 09/13/04): Patients receive epirubicin IV over 15 minutes and docetaxel IV over 60 minutes on day 1 and pegfilgrastim subcutaneously on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with objective response after 6 courses may receive additional therapy at the discretion of the physician.

Group 2 (14-day regimen): Patients receive epirubicin IV over 15 minutes and docetaxel IV over 60 minutes on day 1 and pegfilgrastim subcutaneously on day 2. Treatment repeats every 14 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients with objective response after 8 courses may receive additional therapy at the discretion of the physician.

Cohorts of 3-6 patients receive escalating doses of epirubicin and docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase II:

Group 1 (21-day regimen) (closed to accrual as of 5/10/06): Patients receive treatment as in phase I with epirubicin and docetaxel at the recommended Phase II dose.

Group 2 (14-day regimen): Patients receive treatment as in phase I with epirubicin and docetaxel at the recommended Phase II dose.

Patients are followed at 1 month, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 90 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed invasive adenocarcinoma of the breast, meeting any of the following criteria:

    • T4, NX, M0
    • Any T, N2-N3, M0
    • Inflammatory breast cancer (redness over at least one-third of the breast), M0
  • No evidence of metastatic disease by chest x-ray, abdominal ultrasound or CT scan and bone scan
  • Diagnosed within the past 8 weeks
  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

Age

  • 16 and over

Sex

  • Female

Menopausal status

  • Not specified

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute granulocyte count at least 2,000/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 10 g/dL

Hepatic

  • Bilirubin less than upper limit of normal (ULN)
  • Must meet criteria for 1 of the following:

    • ALT and AST no greater than 1.5 times ULN AND alkaline phosphatase no greater than 2.5 times ULN
    • ALT and AST normal AND alkaline phosphatase no greater than 5 times ULN

Renal

  • Creatinine no greater than 1.5 times ULN

Cardiovascular

  • Resting LVEF normal by MUGA or echocardiogram
  • No congestive heart failure
  • No angina pectoris
  • No myocardial infarction within the past year
  • No uncontrolled hypertension
  • No uncontrolled arrhythmias

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective non-hormonal contraception
  • No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix
  • No symptomatic peripheral neuropathy grade 2 or greater
  • No active infection
  • No history of significant neurological or psychiatric disorders, including dementia or seizures
  • No peptic ulcer
  • No unstable diabetes mellitus
  • No contraindication to dexamethasone
  • No known sensitivity to E. coli-derived or polyethylene glycol products
  • Willing to undergo core biopsies once prior to registration and core biopsies at 2 other timepoints while on study
  • Geographically accessible for treatment and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior immunotherapy for breast cancer

Chemotherapy

  • No prior chemotherapy for breast cancer

Endocrine therapy

  • No prior hormonal therapy for breast cancer
  • No concurrent corticosteroids except for premedication or hypersensitivity reaction
  • No concurrent oral contraception

Radiotherapy

  • No prior radiotherapy for breast cancer

Surgery

  • No prior surgery for breast cancer other than biopsy

Other

  • No prior systemic therapy for breast cancer
  • No other concurrent investigational drugs or anticancer treatment
  • No concurrent preventative IV antibiotics
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00066443

Locations
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, New Brunswick
Atlantic Health Sciences Corporation
Saint John, New Brunswick, Canada, E2L 4L2
Canada, Ontario
Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
CHA-Hopital Du St-Sacrement
Quebec City, Quebec, Canada, G1S 4L8
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Maureen E. Trudeau, BSc, MA, MD, FRCPC Edmond Odette Cancer Centre at Sunnybrook
  More Information

Additional Information:
Publications:
Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00066443     History of Changes
Other Study ID Numbers: MA22, CAN-NCIC-MA22, CDR0000316237
Study First Received: August 6, 2003
Last Updated: January 16, 2014
Health Authority: Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
inflammatory breast cancer

Additional relevant MeSH terms:
Inflammatory Breast Neoplasms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Epirubicin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014