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

Sponsor

NCIC Clinical Trials Group (Other)

Overall Status

Completed

CT.gov ID

NCT00066443

Collaborator

(none)

Enrollment

Locations

Arm

130.7

Actual Duration (Months)

18.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: pegfilgrastim Drug: docetaxel Drug: epirubicin hydrochloride	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

93 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Actual Study Start Date :

Feb 25, 2003

Actual Primary Completion Date :

Jan 6, 2010

Actual Study Completion Date :

Jan 16, 2014

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Toxic effects [7 years]
Findings were presented at ASCO 2010
Response (phase II) [12 years]
Response was presented at ASCO 2010. Duration of response will be analyzed in 2015

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
2	Atlantic Health Sciences Corporation	Saint John	New Brunswick	Canada	E2L 4L2
3	Odette Cancer Centre	Toronto	Ontario	Canada	M4N 3M5
4	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
5	CHA-Hopital Du St-Sacrement	Quebec City	Quebec	Canada	G1S 4L8