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| Sponsor: | NCIC Clinical Trials Group |
|---|---|
| Collaborators: |
North Central Cancer Treatment Group Southwest Oncology Group |
| Information provided by (Responsible Party): | NCIC Clinical Trials Group |
| ClinicalTrials.gov Identifier: | NCT00014222 |
Purpose
RATIONALE:
PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy given with or without epoetin alfa in treating women who have undergone surgery for stage I, stage II, or stage III breast cancer.
| Condition | Intervention | Phase |
|---|---|---|
|
Breast Cancer |
Biological: epoetin alfa Biological: filgrastim Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: epirubicin hydrochloride Drug: fluorouracil Drug: paclitaxel |
Phase III |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase III Adjuvant Trial Of Sequenced EC + Filgrastim + Epoetin Alfa Followed By Paclitaxel Versus Sequenced AC Followed By Paclitaxel Versus CEF As Therapy For Premenopausal Women And Early Postmenopausal Women Who Have Had Potentially Curative Surgery For Node Positive Or High Risk Node Negative Breast Cancer |
| Enrollment: | 2104 |
| Study Start Date: | December 2000 |
| Estimated Study Completion Date: | December 2015 |
| Primary Completion Date: | October 2006 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Arm 1: CEF
6 cycles - q 28 days (6 months) - Cyclophosphamide 75 mg/m2 - po - Days 1-14 - Epirubicin 60 mg/m2 - IV - Days 1 and 8 - 5 Fluorouracil: 500mg/m2 - IV - Days 1 and 8 + Continuous Antibiotic Prophylaxis with Cotrimoxazole 960 mg (i.e.2x480 mg tablets) po-bid or Ciprofloxacin 500 mg - po-bid
|
Drug: cyclophosphamide
75, 600 and 830 mg/m2
Drug: epirubicin hydrochloride
60 mg/m2
Drug: fluorouracil
500mg/m2
|
|
Active Comparator: Arm 2: EC/T
6 cycles - q 14 days (3 months) - Epirubicin 120 mg/m2 - IV - Day 1 - Cyclophosphamide 830 mg/m2 - IV - Day 1 - Filgrastim 5μg/kg/d - SC - Days 2 - 13 + Epoetin Alfa 40,000 IU - SC - once weekly (to begin within 1 week after start of protocol therapy as needed) 21 days from last administration of EC ARM 1 (CEF) ARM 2 (EC/T) 4 cycles - q 21 days (3 months) - Adriamycin 60 mg/m2 - IV - Day 1 - Cyclophosphamide 600 mg/m2 - IV - Day 1 - 21 days from last administration of AC 4 cycles - q 21 days (3 months) - Paclitaxel 175 mg/m2 IV 3 hour infusion ARM 3 (AC/T) 4 cycles - q 21 days (3 months) Paclitaxel 175 mg/m2 IV 3 hour infusion + Filgrastim 5μg/kg/d - SC - Days 2 - 13 + Epoetin Alfa 40,000 IU - SC - once weekly as needed |
Biological: epoetin alfa
40,000 IU
Biological: filgrastim
830 mg/m2 - IV - Day 1
Drug: cyclophosphamide
75, 600 and 830 mg/m2
Drug: doxorubicin hydrochloride
60 mg/m2
Drug: paclitaxel
175 mg/m2
|
|
Active Comparator: Arm 3: AC/T
4 cycles - q 21 days (3 months) - Adriamycin 60 mg/m2 - IV - Day 1 - Cyclophosphamide 600 mg/m2 - IV - Day 1 21 days from last administration of AC 4 cycles - q 21 days (3 months) - Paclitaxel 175 mg/m2 IV 3 hour infusion
|
Drug: cyclophosphamide
75, 600 and 830 mg/m2
Drug: doxorubicin hydrochloride
60 mg/m2
Drug: paclitaxel
175 mg/m2
|
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of positive nodes (0 vs 1-3 vs 4-10 vs more than 10), type of prior surgery (total vs partial mastectomy), and estrogen receptor status (positive vs negative). Patients are randomized to one of three treatment arms.
Beginning 21 days after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel as in arm II.
Treatment in all arms continues in the absence of disease progression or unacceptable toxicity.
All receptor positive patients receive oral tamoxifen or anastrozole (if tamoxifen is contraindicated) for 5 years after completion of chemotherapy.
Quality of life is assessed at baseline, day 1 of cycles 2, 3 4 and 6 (arm I), days 1 of cycles 3 and and day 1 of cycles 1 and 4 of paclitaxel (arm II), day 1 of cycles 2 and 3, day 1 of cycles 1 and 4 of paclitaxel, (arm III), 9 months, 12 months, and then annually thereafter until 5 years
Patients are followed at 9 months, 12 months, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 2,100 patients (700 per treatment arm) will be accrued for this study within 4 years.
Eligibility| Ages Eligible for Study: | up to 60 Years |
| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically confirmed adenocarcinoma of the breast that is potentially curable
Previously treated with one of the following:
Axillary node positive
Negative nodes allowed if the tumor is ≥ 1 cm and 1 or more of the following criteria defining high-risk node-negative disease are met:
Hormone receptor status:
PATIENT CHARACTERISTICS:
Age:
Sex:
Menopausal status:
Performance status:
Life expectancy:
Hematopoietic:
Hepatic:
Renal:
Cardiovascular:
Other:
No other malignancy except:
PRIOR CONCURRENT THERAPY:
Biologic therapy:
No concurrent pegfilgrastim or darbepoetin alfa (Arm II)
Chemotherapy:
Endocrine therapy:
Radiotherapy:
Surgery:
Other:
Contacts and Locations
Show 78 Study Locations| Study Chair: | Mark N. Levine, MD | Margaret and Charles Juravinski Cancer Centre |
| Study Chair: | Edith A. Perez, MD | Mayo Clinic |
| Study Chair: | Kathy S. Albain, MD | Loyola University |
More Information
| Responsible Party: | NCIC Clinical Trials Group |
| ClinicalTrials.gov Identifier: | NCT00014222 History of Changes |
| Other Study ID Numbers: | MA21, CAN-NCIC-MA21, AMGEN-CAN-NCIC-MA21, NCCTG-CAN-NCIC-MA21, BMS-CAN-NCIC-MA21, JANSSEN-ORTHO-CAN-NCIC-MA21, PFIZER-CAN-NCIC-MA21, SWOG-CAN-NCIC-MA21, CDR0000068520 |
| Study First Received: | April 10, 2001 |
| Last Updated: | October 28, 2011 |
| Health Authority: | Canada: Health Canada |
|
stage I breast cancer stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer |
|
Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Cyclophosphamide Fluorouracil Doxorubicin Epirubicin Paclitaxel Lenograstim Epoetin Alfa Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antibiotics, Antineoplastic Hematinics Hematologic Agents Antimetabolites Antimetabolites, Antineoplastic Tubulin Modulators Antimitotic Agents |