Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer

Unicancer

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Biological: Trastuzumab; Drug: Fluorouracil; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: docetaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT00054587

EU-20236

PACS04 (Other Identifier)

FRE-FNCLCC-PACS-04/0005

UC-0140/0005 - PACS 04

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. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which regimen of chemotherapy plus radiation therapy with or without trastuzumab is more effective in treating breast cancer.

PURPOSE: Randomized phase III trial to compare two different chemotherapy regimens plus radiation therapy with or without trastuzumab in treating women who have breast cancer that has spread to lymph nodes in the axilla (under the arm).

Full description

OBJECTIVES:

• Compare the efficacy of adjuvant cyclophosphamide, epirubicin, and fluorouracil vs adjuvant docetaxel and epirubicin, in terms of 5-year survival without relapse, in women with nonmetastatic adenocarcinoma of the breast with lymph node invasion.
• Determine survival of patients treated with these regimens.
• Compare the tolerability of trastuzumab (Herceptin) in patients treated with these regimens.
• Determine the efficacy and tolerability of trastuzumab in patients with hormone receptor-positive tumors.
• Evaluate the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center. Patients are treated in 2 parts.

• Part I: Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive fluorouracil IV, or epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy 5 days a week for 5 weeks.
  • Arm II: Patients receive epirubicin IV over 10 minutes and docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy as in arm I.

Patients with HER2/neu-positive tumors then proceed to part II. Patients with HER2/neu-negative tumors receive no further treatment.

Patients with hormone (estrogen or progesterone) receptor-positive tumors also receive oral tamoxifen daily beginning after chemotherapy is completed and continuing for 5 years.

• Part II: Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes every 3 weeks for 1 year.
  • Arm II: Patients are followed without treatment. Patients not receiving trastuzumab are followed at 4 months, 6 months, every 4 months for 1 year, and then every 6 months for 3 years. Patients receiving trastuzumab are followed at 4 months and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 2,600 patients will be accrued for this study within 3 years.

Enrollment: 3,010 patients

Sex: Female

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed nonmetastatic, unilateral adenocarcinoma of the breast

  • Axillary lymph node invasion (N1, N2, or N3)
  • No cutaneous invasion
  • No T4a or greater disease

• No clinically or radiologically suspected metastases

• No clinically or radiologically suspected contralateral lesion

• No deeply adherent or inflammatory disease

• Complete surgical resection performed, including removal of at least 5 lymph nodes, and with no residual tumor, within the past 42 days

• No prior breast cancer

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age

• 18 to 64

Sex

• Female

Menopausal status

• Not specified

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• ALT and AST no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN
• Bilirubin no greater than ULN
• Hepatitis B and hepatitis C negative
• No hepatic dysfunction

Renal

• Creatinine less than 1.3 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular

• ECHO normal
• LVEF at least 50%

Pulmonary

• FEV normal
• No dyspnea at rest
• No supplemental oxygen dependence

Other

• Not pregnant
• Fertile patients must use effective contraception
• HIV negative
• No active infection
• No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• No contraindication to anthracycline therapy
• No chronic medical or psychological condition
• No geographic or social reason that would preclude study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 4 weeks since prior chemotherapy
• No other concurrent chemotherapy
• No contraindication to anthracycline therapy

Endocrine therapy

• No prior hormonal therapy

Radiotherapy

• No prior radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 4 weeks since prior experimental therapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3,010 participants in 2 patient groups

6 FEC

Active Comparator group

Description:

Patients receive fluorouracil IV, or epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy 5 days a week for 5 weeks.

Treatment:

Drug: Cyclophosphamide

Drug: Fluorouracil

Drug: Epirubicin

Biological: Trastuzumab

6 DE

Experimental group

Description:

Patients receive epirubicin IV over 10 minutes and docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy as in arm I

Treatment:

Drug: docetaxel

Drug: Epirubicin

Biological: Trastuzumab