Clinical trial NCT00066443: Epirubicin, Docetaxel, and Pegfilgrastim in Treating Women With Locally Advanced or Inflammatory Breast Cancer
Official title: A Phase I/II Study Of Increasing Doses Of Epirubicin And Docetaxel Plus Pegfilgrastim For Locally Advanced Or Inflammatory Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
inflammatory breast cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2003-08-07
Enrollment: 93
Sex: FEMALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Toxic effects
timeFrame: 7 years
measure: Response (phase II)
timeFrame: 12 years
Secondary outcomes:
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Saint John
country: Canada
facility: Atlantic Health Sciences Corporation
state: New Brunswick
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
city: Quebec City
country: Canada
facility: CHA-Hopital Du St-Sacrement
state: Quebec
Study officials:
affiliation: Toronto Sunnybrook Regional Cancer Centre
name: Maureen E. Trudeau, BSc, MA, MD, FRCPC
role: STUDY_CHAIR
References:
citation: 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. doi: 10.1007/s10549-009-0531-x.
citation: Trudeau ME, Chapman JA, Guo B, Clemons MJ, Dent RA, Jong RA, Kahn HJ, Pritchard KI, Han L, O'Brien P, Shepherd LE, Parissenti AM. A phase I/II trial of epirubicin and docetaxel in locally advanced breast cancer (LABC) on 2-weekly or 3-weekly schedules: NCIC CTG MA.22. Springerplus. 2015 Oct 21;4:631. doi: 10.1186/s40064-015-1392-x. eCollection 2015.
citation: Parissenti AM, Guo B, Pritzker LB, Pritzker KP, Wang X, Zhu M, Shepherd LE, Trudeau ME. Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy. Breast Cancer Res Treat. 2015 Aug;153(1):135-44. doi: 10.1007/s10549-015-3498-9. Epub 2015 Jul 25.
citation: Pritzker K, Pritzker L, Generali D, Bottini A, Cappelletti MR, Guo B, Parissenti A, Trudeau M. RNA Disruption and Drug Response in Breast Cancer Primary Systemic Therapy. J Natl Cancer Inst Monogr. 2015 May;2015(51):76-80. doi: 10.1093/jncimonographs/lgv015.