Clinical trial NCT00006110: Multimodality Treatment for Women With Stage II, Stage III, or Stage IV Breast Cancer
Official title: Nonrandomized Ph II Study of Multimodality Therapy for Stg IIB, IIIA/B, or Stg IV Breast Cancer w/4 Cycles of Adriamycin and Cytoxan (AC),Followed by 12 Weeks of Paclitaxel w/ or w/o Herceptin Followed by Local Therapy Followed by Wkly Herceptin or no Additional Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage II breast cancer
stage IV breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
inflammatory breast cancer
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2003-01-27
Enrollment: 82
Sex: FEMALE
Minimum age (years): 1
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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. Combining chemotherapy, monoclonal antibody therapy, and surgery may be a more effective treatment for breast cancer.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy, monoclonal antibody therapy, and surgery in treating women who have stage II, stage III, or stage IV breast cancer.

Detailed description: OBJECTIVES:

* Determine the cardiac and other toxicity of paclitaxel when administered with trastuzumab (Herceptin) after doxorubicin and cyclophosphamide in women with stage IIB, IIIA, IIIB, IIIC, or previously untreated stage IV breast cancer.
* Determine whether the addition of paclitaxel with or without trastuzumab to conventional breast cancer adjuvant therapy (doxorubicin and cyclophosphamide) further decreases tumor size and the number of positive axillary nodes in these patients.
* Determine the 5-year disease-free survival and overall survival of patients treated with these regimens.
* Determine whether the initial pathologic response in patients receiving neoadjuvant therapy correlates with the eventual 5-year disease-free survival or overall survival.
* Compare the number of patients eligible for breast-conserving cancer surgery after treatment with doxorubicin and cyclophosphamide vs paclitaxel and trastuzumab.
* Correlate clinical and radiographic response rate with pathologic response rate in the primary tumor and axillary lymph nodes and determine which parameter best determines the pathologic response rate in patients treated with these regimens.

OUTLINE: Patients either received neoadjuvant therapy (HER-2 overexpressing and non-overexpressing patients) or adjuvant therapy (HER-2 overexpressing patients only).

* Neoadjuvant therapy: Patients receive one of two treatment regimens.

  * Regimen I (HER-2 non-overexpressing patients or HER-2 overexpressing patients who refuse trastuzumab (Herceptin) therapy): Patients receive doxorubicin IV and cyclophosphamide IV over 30 minutes and paclitaxel IV over 3 hours on day 1 every 3 weeks for a total of 4 courses. Patients then undergo surgery with or without adjuvant radiotherapy and/or oral tamoxifen.
  * Regimen II (HER-2 overexpressing patients only): Patients receive doxorubicin and cyclophosphamide as in regimen I. After completion of course 4, patients receive paclitaxel IV and trastuzumab IV over 90-150 minutes weekly on weeks 13-24. Patients then undergo surgery with or without adjuvant radiotherapy. Patients then receive trastuzumab IV over 30 minutes weekly on weeks 29-69 if they did not receive radiotherapy or on weeks 36-76 if they did receive radiotherapy.
* Adjuvant therapy: Patients who receive adjuvant therapy (HER-2 overexpressing patients only) receive doxorubicin IV and cyclophosphamide IV over 30 minutes on day 1 every 3 weeks for a total of 4 courses. After completion of course 4, patients receive paclitaxel IV and trastuzumab IV over 90 minutes weekly on weeks 13-24. Patients then may undergo radiotherapy followed by trastuzumab IV over 30 minutes weekly on weeks 29-69 if they did not receive radiotherapy or on weeks 36-76 if they did receive radiotherapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 125 patients (100 in the neoadjuvant group and 25 in the adjuvant group) will be accrued for this study within 5 years.

Eligibility criteria: Inclusion Criteria

* Histologically confirmed stage IIB, IIIA, IIIB, IIIC, or previously untreated stage IV primary carcinoma of the breast

  * Fine needle aspiration, core needle biopsy, or incisional biopsy allowed
  * No excisional biopsy
  * Any of the following:

    * Tumor size 2, Nodes 1 (T2N1) or tumor size 3 nodes 0 (T3N0)
    * Any T with N2 (including axillary lymph nodes matted to one another) or N3
    * Any T4, including inflammatory breast cancer
    * Adjuvant patients with at least 4 positive lymph nodes and HER-2 overexpressing tumor
    * Supraclavicular or infraclavicular positive lymph nodes without distant metastases
    * Distant metastases with measurable disease in breast or lymph nodes
* Synchronous bilateral primary breast cancer allowed if the more serious cancer meets entry criteria
* Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Age: Not specified

Sex: Female

Menopausal status: Not specified

Performance status: Not specified

Life expectancy: Not specified

Hematopoietic:

White cell count \> 3000 / mm3 Platelet count \> 100,000 / mm3

Hemoglobin \> 9 mg / dl Bilirubin \< 1.5 x normal Creatinine \< 1.5 x normal left ventricular ejection fraction (LVEF) normal by resting nuclear ventriculogram Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

Exclusions

Prior malignancies except:

Effectively treated squamous cell or basal cell skin cancer Carcinoma in situ of the cervix that has been curatively treated by surgery alone Nonbreast malignancy from which patient has been disease-free for 5 years and is at low risk of recurrence

Primary outcomes:
measure: Cardiac Toxicity of Weekly Taxol Given With Weekly Herceptin When Delivered Immediately Following Four Cycles of Standard Dose AC.
timeFrame: 78 weeks (1.5 years)
Secondary outcomes:
measure: Overall Response
timeFrame: 78 weeks (1.5 years)
measure: Disease-free Survival (DFS) in Patients Receiving and Not Receiving Herceptin®.
timeFrame: 5 years
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Lisa A. Carey, MD
role: STUDY_CHAIR
References: