Paclitaxel and Radiation Therapy in Treating Patients Undergoing Surgery for Stage II or Stage III Breast Cancer

Vanderbilt University Medical Center

Status

Completed

Conditions

Breast Cancer

Treatments

Drug: Hormonal Therapy

Radiation: Radiation therapy with concurrent Paclitaxel

Procedure: therapeutic surgical procedure

Drug: neoadjuvant therapy

Drug: Post-operative adjuvant therapy

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00647218

VU-VICC-BRE-9936

P30CA068485 (U.S. NIH Grant/Contract)

VCC BRE 9936

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving paclitaxel and radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This clinical trial is studying how well giving paclitaxel together with radiation therapy works in treating patients undergoing surgery for stage II or stage III breast cancer.

Full description

OBJECTIVES:

Primary

Evaluate the efficacy of paclitaxel and concurrent radiotherapy (as measured by pathologic response rates) in patients with stage II or III breast cancer.

Secondary

Evaluate the toxicities of this treatment regimen.
Correlate paclitaxel-induced tumor response with local recurrence-free survival, distant disease-free survival, and overall survival.
Evaluate protein expression profiles by mass spectrometry in biopsy material and blood specimens collected before and after treatment with paclitaxel.

OUTLINE:

Neoadjuvant chemotherapy: Patients receive paclitaxel IV over 3 hours on day 1. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Chemoradiotherapy: Beginning 3-4 weeks after completion of neoadjuvant chemotherapy, patients receive paclitaxel IV over 1 hour twice weekly and undergo radiotherapy once daily, 5 days a week, for 6½ weeks.
Surgery: At 6-8 weeks after completion of chemoradiotherapy, patients undergo surgical resection (e.g., modified radical mastectomy or lumpectomy and axillary node dissection).
Adjuvant chemotherapy: Beginning 4-6 weeks after surgery, patients receive doxorubicin hydrochloride IV over 20 minutes and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Hormonal therapy: After completion of adjuvant chemotherapy, patients with estrogen receptor- and/or progesterone receptor-positive tumor receive hormonal therapy at the discretion of the treating physician.

Patients undergo blood and tissue sample collection periodically to analyze changes in cell cycle by flow cytometry; antibody assays; kinase assays for cyclin B1/CDC2; genetic assays for p53, p21, and other molecular markers; and protein expression assays by mass spectrometry.

After completion of study therapy, patients are followed periodically.

Enrollment

38 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically documented invasive carcinoma of the breast*
- Tumor ≥ 2 cm in greatest dimension (e.g., T2-4) and any nodal status (e.g., N0-3), including locally advanced disease, as defined by the following criteria:
  - Primary tumor ≥ 5 cm
  - Tumor of any size with direct extension to the chest wall or skin
  - Inflammatory breast cancer (T4d)
  - Metastasis to ipsilateral internal mammary node
  - Ipsilateral lymph nodes that are clinically fixed to each other or to other structures (N2) NOTE: *Diagnosis may be made by core or tru-cut biopsies
Measurable or evaluable tumor
- Measurable disease is defined as any mass that can be reproducibly measured in two perpendicular dimensions
- Evaluable disease is defined as any lesion visible by mammogram or palpable by physical exam that does not fit the above criteria of measurability
Planning to undergo breast conservation surgery
Willing to undergo AND is a candidate for radiotherapy, in the judgement of the treating radiation oncologist
No evidence of distant metastatic disease (e.g., lung, liver, bone, brain)
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Menopausal status not specified
ECOG performance status 0-1
WBC ≥ 3,000/mm^3
Platelet count ≥ 100,000/mm^3
Creatinine ≤ 1.5 times upper limit of normal (ULN)
Bilirubin ≤ 1.5 times ULN
Left ventricular ejection fraction ≥ 45%
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other malignancies within the past 5 years, except curatively treated nonmelanomatous skin cancer or carcinoma in situ of the cervix
No history of hypersensitivity reaction to products containing polysorbate 80 (Tween 80)
No serious medical illness that, in the judgment of the treating physician, places the patient at risk
No peripheral neuropathy ≥ grade 2

PRIOR CONCURRENT THERAPY:

Prior tamoxifen as chemoprevention allowed
No prior radiotherapy to the ipsilateral breast
- Prior radiotherapy to the contralateral breast is allowed
No prior chemotherapy