S0012 Doxorubicin, Cyclophosphamide, and Paclitaxel With or Without Filgrastim in Treating Women With Inflammatory or Locally Advanced Breast Cancer

SWOG Cancer Research Network

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Drug: paclitaxel; Drug: doxorubicin; Biological: filgrastim; Drug: cyclophosphamide; Procedure: surgery

Study type: Interventional

Funder types: NETWORK; NIH

Identifiers

NCT00016406

CDR0000068630

U10CA032102 (U.S. NIH Grant/Contract)

S0012 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether combination chemotherapy is more effective with or without filgrastim in treating breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of combining doxorubicin, cyclophosphamide, and paclitaxel with or without filgrastim in treating women who have inflammatory or locally advanced breast cancer.

Full description

OBJECTIVES:

• Compare the microscopic pathologic response rates in women with inflammatory or locally advanced breast cancer treated with standard neoadjuvant doxorubicin and cyclophosphamide followed by weekly paclitaxel vs weekly doxorubicin and daily oral cyclophosphamide with filgrastim (G-CSF) followed by weekly paclitaxel.
• Compare the toxic effects of these regimens in this patient population.
• Compare the delivered dose intensity of these regimens in this patient population.
• Evaluate the association between microscopic pathologic complete response and clinical complete response at the primary tumor site in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease status (inflammatory vs other). Patients are randomized to one of two treatment arms.

• Arm I: Patients receive doxorubicin IV followed by cyclophosphamide IV on day 1. Treatment repeats every 21 days for a total of 5 courses in the absence of disease progression or unacceptable toxicity. Three weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour weekly on day 1 for a total of 12 weeks.
• Arm II: Patients receive doxorubicin IV on day 1, oral cyclophosphamide on days 1-7, and filgrastim (G-CSF) subcutaneously on days 2-7. Treatment repeats weekly for a total of 15 courses of doxorubicin and cyclophosphamide and 16 courses of G-CSF in the absence of disease progression or unacceptable toxicity. One week after completion of G-CSF, patients receive paclitaxel as in arm I.

Within 3-6 weeks after completion of chemotherapy, patients with stable or responsive disease undergo surgical resection of tumor and affected nodes.

After surgery, patients may receive radiotherapy or additional chemotherapy and/or hormonal therapy at the discretion of the treating physician.

Patients are followed every 6 months for 1 year and then annually for 4 years.

PROJECTED ACCRUAL: A total of 350 patients (175 per treatment arm) will be accrued for this study within 3 years.

Enrollment: 399 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed inflammatory or locally advanced breast cancer

  • Stage IIB (T3, N0, M0), IIIA (T3, N1-2, M0 or T0-2, N2, M0), or IIIB (T4, any N, M0 or any T, N3, M0)

  • Unresectable or otherwise appropriate for neoadjuvant therapy

  • Confirmed by core needle or incisional biopsy

    • Punch biopsy allowed if invasive disease is documented

• No distant metastases

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• Not specified

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• SGOT or SGPT no greater than 2 times ULN

Renal:

• Creatinine no greater than ULN

Cardiovascular:

• No congestive heart failure or angina pectoris
• LVEF greater than lower limit of normal

Other:

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• HIV negative
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for breast cancer

Endocrine therapy:

• No prior hormonal therapy for breast cancer

Radiotherapy:

• No prior radiotherapy for breast cancer

Surgery:

• No prior definitive surgery for breast cancer

Other:

• No other concurrent anticancer therapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

399 participants in 2 patient groups

AC followed by P

Active Comparator group

Description:

doxorubicin and cyclophosphamide followed by paclitaxel followed by surgery

Treatment:

Drug: paclitaxel

Drug: cyclophosphamide

Procedure: surgery

Drug: doxorubicin

AC+G followed by P

Experimental group

Description:

weekly doxorubicin and daily cyclophosphamide with filgrastim followed by paclitaxel followed by surgery

Treatment:

Drug: paclitaxel

Drug: cyclophosphamide

Procedure: surgery

Biological: filgrastim

Drug: doxorubicin