Epirubicin, Docetaxel, and Pegfilgrastim in Treating Women With Locally Advanced or Inflammatory Breast Cancer - Full Text View

Sponsor:	NCIC Clinical Trials Group
Information provided by (Responsible Party):	NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:	NCT00066443

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 I Phase II

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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Epirubicin hydrochloride Epirubicin Docetaxel Pegfilgrastim

U.S. FDA Resources

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
Estimated Study Completion Date:	June 2014
Estimated Primary Completion Date:	June 2014 (Final data collection date for primary outcome measure)

Intervention Details:

Dose escalation schedule A&B = 6mg fixed dose once per cycle on day 2

Dose Escalation schedule A = 75-85 mg/m2 Dose Escalation schedule B = 50-75 mg/m2

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

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:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Parissenti AM, Chapman JA, Kahn HJ, Guo B, Han L, O'Brien P, Clemons MP, Jong R, Dent R, Fitzgerald B, Pritchard KI, Shepherd LE, Trudeau ME. Association of low tumor RNA integrity with response to chemotherapy in breast cancer patients. Breast Cancer Res Treat. 2010 Jan;119(2):347-56.

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:	September 13, 2011
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:

Breast Neoplasms
Inflammatory Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

Epirubicin
Docetaxel
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012