Clinical trial NCT00093795
Conditions: Breast Cancer
Keywords: stage II breast cancer stage IIIA breast cancer stage IIIC breast cancer
Sponsor: NSABP Foundation Inc
Start date: 2004-10-01; Completion date: 2016-06-01
Enrollment: 4894 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Drugs used in chemotherapy, such as docetaxel, doxorubicin , cyclophosphamide, paclitaxel, and gemcitabine work in different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy after surgery may kill any remaining tumor cells.

PURPOSE: This randomized phase III trial is studying three different combination chemotherapy regimens and comparing how well they work in treating women who have undergone surgery for node-positive breast cancer.

Detailed description:
OBJECTIVES:

Primary

* Compare disease-free survival in women with node-positive breast cancer treated with 3 different adjuvant chemotherapy regimens comprising dose-dense doxorubicin, cyclophosphamide, paclitaxel, and gemcitabine vs docetaxel, doxorubicin, and cyclophosphamide vs dose-dense doxorubicin, cyclophosphamide, and paclitaxel.

Secondary

* Compare overall survival, recurrence-free interval, and distant recurrence-free interval, in patients treated with these regimens.
* Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of positive lymph nodes (1-3 vs 4-9 vs ≥ 10), hormone receptor status (estrogen receptor \[ER\]- and progesterone receptor \[PgR\]- negative vs ER- and/or PgR-positive), type of prior surgery and planned radiotherapy (lumpectomy and local radiotherapy \[RT\] without regional RT vs lumpectomy and local RT with regional RT vs mastectomy without RT vs mastectomy with local or regional RT). Patients are randomized to 1 of 3 treatment arms.

* Group 1: Patients receive doxorubicin IV over 15 minutes, cyclophosphamide IV over 30 minutes, and docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for 6 courses.
* Group 2: Patients receive AC chemotherapy comprising doxorubicin IV over 15 minutes and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 14 days for 4 courses. Beginning 14 days after the last dose of AC, patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 14 days for 4 courses.
* Group 3: Patients receive AC chemotherapy as in Group 2. Beginning 14 days after the last dose of AC, patients receive paclitaxel as in Group 2 and gemcitabine IV over 30-60 minutes on day 1. Treatment repeats every 14 days for 4 courses.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Beginning 3-12 weeks after the last dose of chemotherapy, patients with ER-positive and/or PgR-positive tumors receive hormonal therapy.

Beginning no sooner than 3 weeks after the last dose of chemotherapy, patients treated with lumpectomy undergo whole-breast radiotherapy. Patients treated with mastectomy may undergo chest wall and/or regional nodal radiotherapy.

Patients are followed every 6 months for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 4,800 patients will be accrued for this study within 4 years.

Arms: arm 1: Doxorubicin, cyclophosphamide, and docetaxel. arm 2: Doxorubicin, cyclophosphamide, and paclitaxel arm 3: Doxorubicin, cyclophosphamide, paclitaxel and gemcitabine
Interventions: intervention 1: Cyclophosphamide intervention 2: Docetaxel intervention 3: Gemcitabine intervention 4: Paclitaxel intervention 5: Doxorubicin
Intervention descriptions: intervention 1: Group 1: cyclophosphamide 500 mg/m2 IV every 21 days for 6 cycles

Group 2 and Group 3: cyclophosphamide 600 mg/m2 IV every 14 days for 4 cycles intervention 2: 75 mg/m2 IV every 21 days for 6 cycles intervention 3: 2000 mg/m2 IV every 14 days for 4 cycles intervention 4: 175 mg/m2 IV every 14 days for 4 cycles intervention 5: Group 1: 50 mg/m2 IV every 21 days for 6 cycles

Group 2 and Group 3: 60 mg/m2 IV every 14 days for 4 cycles

Protocol documents: