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

NCT ID: NCT00066443

Last Updated: 2023-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-11-03
• Study Completion Date: 2014-01-16

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pegfilgrastim, docetaxel and epirubicin

Group Type: EXPERIMENTAL

pegfilgrastim

Intervention Type: BIOLOGICAL

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

docetaxel

Intervention Type: DRUG

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

epirubicin hydrochloride

Intervention Type: DRUG

Dose escalation schedule A = 75-120 mg/m2 IV Dose escalation schedule B = 50-90 mg/m2 IV

Interventions

pegfilgrastim

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

Intervention Type: BIOLOGICAL

docetaxel

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

Intervention Type: DRUG

epirubicin hydrochloride

Dose escalation schedule A = 75-120 mg/m2 IV Dose escalation schedule B = 50-90 mg/m2 IV

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 16 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maureen E. Trudeau, BSc, MA, MD, FRCPC

Role: STUDY_CHAIR

Toronto Sunnybrook Regional Cancer Centre

Locations

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Atlantic Health Sciences Corporation

Saint John, New Brunswick, Canada

Odette Cancer Centre

Toronto, Ontario, Canada

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

CHA-Hopital Du St-Sacrement

Québec, Quebec, Canada

Countries

Canada

References

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.

Reference Type: RESULT

PMID: 19771508 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26543765 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26208483 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26063893 (View on PubMed)

Other Identifiers

CAN-NCIC-MA22

Identifier Type: -

Identifier Source: secondary_id

CDR0000316237

Identifier Type: OTHER

Identifier Source: secondary_id

MA22

Identifier Type: -

Identifier Source: org_study_id